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Purpose: The purpose was to evaluate the pathological nature of focal thyroid uptake seen in 11C-Choline PET/CT performed for prostate cancer., Material and Methods: The study was IRB-approved. All 11C-Choline PET/CT exam reports for studies performed between January 01, 2018, and July 30, 2021, in male patients with prostate cancer in our institution were retrospectively reviewed. Exams with "focal thyroid uptake" on their final report were selected. Patients with surgery or ablation in the thyroid prior to the PET/CT, proven parathyroid adenomas or absent thyroid ultrasound were excluded. Repeated PET/CT exams of same patient were excluded. PET images were analyzed visually and semi-quantitatively by measuring the maximum standardized uptake value (SUVmax) of the focal thyroid uptake. Available thyroid ultrasound images, cytology and pathology reports were reviewed. Statistical analyses were performed., Results: Out of 10,047 sequential 11C-Choline PET/CT studies, 318 reports included "focal thyroid uptake." About 128 of these studies were repeat exams and were excluded. Additional 87 patients were excluded, because the uptake was determined to be adjacent, rather than confined to the thyroid gland. Out of the remaining 103 patients, 74 patients had focal thyroid uptake and concurrent thyroid sonographic evaluation. Out of the 74 focal uptakes evaluated with ultrasound, 21 were presumed benign thyroid nodules based on the ultrasound and 53 had further evaluation with biopsy. Sixty three nodules were benign (21 presumed benign on ultrasound and 42 cytology or surgical pathology-proven), 9 nodules were malignant and 2 remained indeterminate. There was no significant difference between the SUVs of the benign and malignant groups (P > .3)., Conclusion: In this retrospective study of patients with prostate cancer who underwent 11C-Choline PET/CT, we identified a group of patients who underwent thyroid ultrasound for incidental finding of focal 11C-Choline thyroid uptake. Incidence of malignancy in this group was 12%. Therefore, further investigation with ultrasound and possibly ultrasound-guided biopsy may be warranted when a choline avid thyroid nodule is found incidentally on choline PET., Competing Interests: The authors have no funding and conflicts of interest to declare., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Gallium-68 (Ga)-PSMA and F-Choline are two radionuclides that have already shown high potential for the detection of prostate cancer. The comparison between these two radionuclides has several advantages in radiation protection. The aim of this prospective study was to identify which of these two radionuclides can help in predicting the equivalent dose using the maximum standard uptake value (SUVmax) of normal organs, the kidneys. Two groups of 40 patients (total n = 80) who underwent PET/CT using Ga or F for diagnosis of prostate cancer between April 2018 and December 2018 at the American University of Beirut Medical Center were included. First, the dose rates were measured after 1 h of radionuclide uptake at 1 m distance with background of 0.015 μSv h. Then, SUVmax for kidneys were determined from images obtained with PET/CT 1 h after injection of both radionuclides. The ratios of the equivalent doses to the SUVmax for kidneys were compared for both Ga-PSMA and F-Choline. There is a positive moderate relationship between the SUVmax for kidneys and the Ga dose rate after 1 h of injection at 1 m distance from the abdomen (p-value = 0.023 < 0.05). This relationship is statistically significant. However, there is a very low negative relationship between the SUVmax kidney and F dose rate after 1 h of injection at 1 m distance from the abdomen (p-value = 0.93 > 0.05). This relationship is not statistically significant. This leads to the suggestion that we can predict the equivalent dose due to Ga by indicating the SUVmax from the PET/CT images.

We present a novel series of radioiodinated tracers and potential theranostics for diseases accompanied by pathological function of proteins involved in choline transport. Unlike choline analogues labeled with 11 C or 18 F that are currently used in the clinic, the iodinated compounds described herein are applicable in positron emission tomography, single-photon emission computed tomography, and potentially in therapy, depending on the iodine isotope selection. Moreover, favorable half-lives of iodine isotopes result in much less challenging synthesis by isotope exchange reaction. Six of the described compounds were nanomolar ligands, and the best compound possessed an affinity 100-fold greater than that of choline. Biodistribution data of 125 I-labeled ligands in human prostate carcinoma bearing (PC-3) mice revealed two compounds with a biodistribution profile superior to that of [ 18 F]fluorocholine.

Aim: To standardize acquisition protocols for 18 F-Choline PET/CT to prevent from urine interference, to determine the best time point for the whole-body study, and to assess whether "dual point" acquisition allows for differentiating malignant vs. benign lesions., Methods: One hundred consecutive patients with prostate cancer were prospectively studied. Immediately after 18 F-Choline injection, a pelvis study was acquired, and a whole-body was subsequently obtained 1 and 2 hours p.i. Mean SUVmax was obtained in regions and for every sequential imaging. Mean analysis (χ 2 ) and SUV percentage change (2/1 hours; 1 hours/0 min) were obtained. Metabolic pattern dynamics were assessed: accumulative vs. clearance. Patient follow-up after therapy and directed classification whenever ethically possible were performed., Results: Fifty-three prostate foci, without disturbing urinary activity was ever found on early images. Accumulative pattern in 42, with percentage increase was: 0 min/1 hour: +16.7% (χ 2 0.94); 1/2 hours: +10,0% (χ 2 0.83). Clearance pattern in 11, with percentage decrease: 0 min/1 hour: -21.4% (χ 2 0.91): -7.7% (χ 2 0.85), corresponding in 7 to initial staging and in 4 post-radiotherapy biochemical recurrence. Every infradiaphragmatic uptake (n: 24) showed accumulative pattern, with percentage increase of +9.1% (χ 2 0.97), all of them depicted on early imaging. As for 12 supradiaphragmantic uptake, 8 of them showed clearance pattern with percentage decrease: -13.0% (χ 2 0.95). Accumulative pattern showed in 4 of them with percentage increase +13.0% (χ 2 0.96), thus being assessed as invasive/malignant. Every bone uptake (n: 18) showed accumulative pattern, with percentage increase: +17.1% (χ 2 0.95), all of them depicted on 1 hour imaging., Conclusions: As for prostate assessment is concerned, dual point at 0 min/1 hour proved to be the best procedure. As for supradiaphragmatic lymph-nodes detection, dual point with 1/2 hours performed best. As for infradiaphragmatic and bone involvement, as well as for inconclusive findings, the 2 hour imaging increased our diagnostic confidence., (Copyright © 2020 Sociedad Española de Medicina Nuclear e Imagen Molecular. Publicado por Elsevier España, S.L.U. All rights reserved.)

Aim: To validate a deep-learning (DL) algorithm for automated quantification of prostate cancer on positron emission tomography/computed tomography (PET/CT) and explore the potential of PET/CT measurements as prognostic biomarkers., Material and Methods: Training of the DL-algorithm regarding prostate volume was performed on manually segmented CT images in 100 patients. Validation of the DL-algorithm was carried out in 45 patients with biopsy-proven hormone-naïve prostate cancer. The automated measurements of prostate volume were compared with manual measurements made independently by two observers. PET/CT measurements of tumour burden based on volume and SUV of abnormal voxels were calculated automatically. Voxels in the co-registered 18 F-choline PET images above a standardized uptake value (SUV) of 2·65, and corresponding to the prostate as defined by the automated segmentation in the CT images, were defined as abnormal. Validation of abnormal voxels was performed by manual segmentation of radiotracer uptake. Agreement between algorithm and observers regarding prostate volume was analysed by Sørensen-Dice index (SDI). Associations between automatically based PET/CT biomarkers and age, prostate-specific antigen (PSA), Gleason score as well as overall survival were evaluated by a univariate Cox regression model., Results: The SDI between the automated and the manual volume segmentations was 0·78 and 0·79, respectively. Automated PET/CT measures reflecting total lesion uptake and the relation between volume of abnormal voxels and total prostate volume were significantly associated with overall survival (P = 0·02), whereas age, PSA, and Gleason score were not., Conclusion: Automated PET/CT biomarkers showed good agreement to manual measurements and were significantly associated with overall survival., (© 2019 The Authors. Clinical Physiology and Functional Imaging published by John Wiley & Sons Ltd on behalf of Scandinavian Society of Clinical Physiology and Nuclear Medicine.)

The aim of this study was to investigate the value of pharmacokinetic modeling for quantifying 11 C-choline uptake in patients with recurrent prostate cancer. Methods: In total, 194 patients with clinically suspected recurrence of prostate cancer underwent 11 C-choline dynamic PET over the pelvic region (0-8 min), followed by a 6-min static acquisition at about 25 min after injection. Regions of interest were drawn over sites of disease identified by a radiologist with experience in nuclear medicine. 11 C-choline uptake and pharmacokinetics were evaluated by SUV, graphical analysis (Patlak plot; K i P ), and 1- and 2-compartment pharmacokinetic models ( K 1 , K 1 / k 2 , k 3 , k 4 , and the macro parameter K i C ). Twenty-four local recurrences, 65 metastatic lymph nodes, 19 osseous metastases, and 60 inflammatory lymph nodes were included in the analysis, which was subsequently repeated for regions of interest placed over the gluteus maximus muscle and adipose tissue as a control. Results: SUV mean and K i P were 3.60 ± 2.16 and 0.28 ± 0.22 min -1 in lesions, compared with 2.11 ± 1.33 and 0.15 ± 0.10 min -1 in muscle and 0.26 ± 0.07 and 0.02 ± 0.01 min -1 in adipose tissue. According to the Akaike information criterion, the 2-compartment irreversible model was most appropriate in 85% of lesions and resulted in a K 1 of 0.79 ± 0.98 min -1 (range, 0.11-7.17 min -1 ), a K 1 / k 2 of 2.92 ± 3.52 (range, 0.31-20.00), a k 3 of 0.36 ± 0.30 min -1 (range, 0.00-1.00 min -1 ) and a K i C of 0.28 ± 0.22 min -1 (range, 0.00-1.33 min -1 ). The Spearman ρ between SUV and K i P , between SUV and K i C , and between K i P and K i C was 0.94, 0.91, and 0.97, respectively, and that between SUV and K 1 , between SUV and K 1 / k 2 , and between SUV and k 3 was 0.70, 0.44, and 0.33, respectively. Malignant lymph nodes exhibited a higher SUV, K i P , and K i C than benign lymph nodes. Conclusion: Although 11 C-choline pharmacokinetic modeling has potential to uncouple the contributions of different processes leading to intracellular entrapment of 11 C-choline, the high correlation between SUV and both K i P and K i C supports the use of simpler SUV methods to evaluate changes in 11 C-choline uptake and metabolism for treatment monitoring., (© 2018 by the Society of Nuclear Medicine and Molecular Imaging.)

Objectives: To test the ability of dynamic 11C-PET / CT to discriminate cancerous tissue from background tissue in patients with localized prostate cancer., Materials and Methods: Twenty-four consecutive patients with prostate cancer were prospectively evaluated with dynamic 11C-choline PET / CT prior to radical prostatectomy. The PET / CT scan was divided into 18 sequences of 5 seconds each, followed by 9 sequences of 60 seconds each. Whole-mount sections of harvested prostates served as reference standards. Volumes of interest were positioned on the dynamic PET / CT images and the following quantitative variables were calculated: perfusion coefficient (K1), washout constant (K2), area under the curve (AUC) at 175 and 630 seconds, and average and maximum standardized uptake values (SUVavg, and SUVmax). Wilcoxon signed-ranks test was used to compare benign and cancerous areas of the prostate., Results: Areas of cancerous tissue were characterized by higher SUVavg and SUVmax than areas of benign tissue (3.67 ± 2.7 vs. 2.08 ± 1.3 and 5.91 ± 4.4 vs. 3.71 ± 3.7, respectively, P < 0.001), in addition to a higher K1 (0.95 ± 0.58 vs. 0.43 ± 0.24, P < 0.001) and greater cumulative tracer uptake, represented by the AUC at 175 and 630 seconds (P <0.001). No associations were found between dynamic parameters and preoperative prostate specific antigen level or Gleason score., Conclusions: In this pilot study, 11C-choline PET / CT demonstrated increased tracer uptake with higher values of static and dynamic parameters in areas of prostate cancer compared to areas of benign tissue. Larger studies are warranted to validate these results and examine the potential applicability of 11C-choline dynamic PET / CT for the diagnosis of prostate cancer., Competing Interests: Conflict of interest: None declared., (Copyright® by the International Brazilian Journal of Urology.)

Purpose: To investigate the predictive value of [ 18 F]-fluoromethylcholine positron emission tomography/computed tomography (PET/CT)-derived parameters on progression-free survival (PFS) in oligometastatic prostate cancer patients treated with stereotactic body radiation therapy (SBRT)., Methods and Materials: In [ 18 F]-fluoromethylcholine PET/CT scans of 40 consecutive patients with ≤4 metachronous metastases treated with SBRT we retrospectively measured the number of metastases, standardized uptake values (SUV mean , SUV max , SUV peak ), metabolically active tumor volume (MATV), and total lesion choline uptake. Partial-volume correction was applied using the iterative deconvolution Lucy-Richardson algorithm., Results: Thirty-seven lymph node and 13 bone metastases were treated with SBRT. Thirty-three patients (82.5%) had 1 lesion, 4 (10%) had 2 lesions, and 3 (7.5%) had 3 lesions. After a median follow-up of 32.6 months (interquartile range, 35.5 months), the median PFS was 11.5 months (95% confidence interval 8.4-14.6 months). Having more than a single metastasis was a significant prognostic factor (hazard ratio 2.74; P = .03), and there was a trend in risk of progression for large MATV (hazard ratio 1.86; P = .10). No SUV or total lesion choline uptake was significantly predictive for PFS, regardless of partial-volume correction. All PET semiquantitative parameters were significantly correlated with each other (P ≤ .013)., Conclusions: The number of choline-avid metastases was a significant prognostic factor for progression after [ 18 F]-fluormethylcholine PET/CT-guided SBRT for recurrent oligometastatic prostate cancer, and there seemed to be a trend in risk of progression for patients with large MATVs. The lesional level of [ 18 F]-fluoromethylcholine uptake was not prognostic for progression., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Prostate Cancer (PCa) represents the most common malignant tumor in men but according to the European Association of Urology (EAU) guidelines, a mass screening for PCa diagnosis should not be performed due to over-diagnosis and over-treatment related problems. An early clinical diagnosis is possible, mainly based on digital rectal examination and Prostatic Specific Agent (PSA) testing. However, the only mandatory test to define the presence of PCa is ultrasound guided-biopsy, obtained on multiple samples, which has also a high prognostic value. In this context, diagnostic imaging plays an important role as confirmed by EAU that in a 2016 update of their guidelines on PCa stated the importance of Positron Emission Tomography (PET) with 11 C- or 18 F-choline combined with computed tomography (CT) to identify local relapse, lymph node involvement and metastatic spread at all stages. Consequently, in 2017, the European Association of Nuclear Medicine (EANM) together with the Society of Nuclear Medicine and Molecular Imaging (SNMMI) published new guidelines for 68 Ga-Prostate Specific Membrane Antigen (PSMA) PET/CT to help physicians in the recommendation, execution and interpretation of PET/CT scans in patients with PCa. Thus, the aim of this 'evidence paper' is to define the current diagnostic algorithm in PCa in order to increase the general level of confidence in approaching such a crucial topic., (Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.)

Introduction: The 11 C/ 18 F-choline is a PET/CT radiopharmaceutical useful in detecting tumors with high lipogenesis. 11 C/ 18 F-choline uptake can occur in physiological conditions or tumors. The knowledge of its bio-distribution is essential to recognize physiologic variants or diagnostic pitfalls. Moreover, few information are available on the bio-distribution of this tracer in female patients. Our aim was to discuss some documented 18 F-choline PET/CT pitfalls in prostate cancer patients. Our secondary aim was to describe the 18 F-choline bio-distribution in the female body., Methods: We collected diagnostic pitfalls in three PET centers examining 1000 prostate cancer by 18 F-choline PET/CT. All pitfalls were ensured by follow-up, imaging and/or histology. We also performed whole body 18 F-choline PET/CT in 5 female patients., Results: 169/1000 (16.9%) patients showed pitfalls not owing to prostate cancer. These findings were due to inflammation, benign tumors while, in 1% of examined patients, a concomitant neoplasm was found. In the female body, the breast showed low physiological uptake., Conclusions: The accurate knowledge of 18 F-choline PET/CT bio-distribution and diagnostic pitfalls is essential. Correlative imaging and histological exam are often necessary to depict pitfalls. In women, the uptake in the breast is due to the physiological gradient of 18 F-choline uptake in the exocrine glands., Advances in Knowledge: Our results confirm the possibility of 18 F-choline uptake in several diseases other than prostate cancer. However, our experience was acquired on a large population and shows that a conspicuous amount of 18 F-choline diagnostic pitfalls are easily recognizable and attributable to inflammation. A new advance in knowledge is the minimal difference in terms of physiological tracer bio-distribution between male and female patients., Implications for Patient Care: The knowledge of the physiological bio-distribution and of the potential pitfalls linked of a tracer could help physicians to choose the best diagnostic and therapeutic approaches for a better patient quality of life., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Over the last decade, 18 F-fluorocholine positron emission tomography/computed tomography (FCH-PET/CT) has gained in popularity for the staging and restaging of patients with prostate cancer (PCa). However, despite abundant literature on the topic, there is a lack of publications on how to actually interpret FCH-PET/CT in a clinical setting. Here we propose a practical, TNM-oriented approach to read FCH-PET/CT, with notes on procedure technique, image display, review sequence and report structure. The purpose of this article is to provide guidance to radiologists, nuclear medicine physicians and residents who are new to FCH-PET/CT, as well as to propose an alternate approach to more experienced physicians.

[(18)F]Fluorocholine ([(18)F]FCH) has been proven to be effective in prostate cancer. Since [(18)F]FCH is classified as a new radiopharmaceutical in Brazil, preclinical safety and efficacy data are required to support clinical trials and to obtain its approval. The aim of this work was to perform acute toxicity, biodistribution, pharmacokinetics, radiation dosimetry and microPET imaging studies of [(18)F]FCH. The results could support its use in nuclear medicine as an important piece of work for regulatory in Brazil., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Purpose: Carbon-11- and fluorine-18-labeled choline derivatives are commonly used in prostate cancer imaging in the clinical setting for staging and re-staging of prostate cancer. Due to a limited detection rate of established positron emission tomography (PET) tracers, there is a clinical need for innovative tumor-specific PET compounds addressing new imaging targets. The aim of this study was to compare the properties of [(18)F]Bombesin (BAY 86-4367) as an innovative biomarker for prostate cancer imaging targeting the gastrin-releasing peptide receptor and [(11)C]Choline ([(11)C]CHO) in a human prostate tumor mouse xenograft model by small animal PET/X-ray computed tomography (CT)., Procedures: We carried out a dual-tracer small animal PET/CT study comparing [(18)F]Bombesin and [(11)C]CHO. The androgen-independent human prostate tumor cell line PC-3 was implanted subcutaneously in the flanks of nu/nu NMRI mice (n = 10) (PET/CT measurements of two [(11)C]Choline mice could not be analyzed due to technical reasons). [(18)F]Bombesin and [(11)C]CHO PET/CT imaging was performed about 3-4 weeks after the implantation of PC-3 cells on two separate days. After the intravenous tail vein injection of 14 MBq [(18)F]Bombesin and 37 MBq [(11)C]CHO, respectively, a dynamic study over 60 min was acquired in list mode using an Inveon animal PET/CT scanner (Siemens Medical Solutions). The sequence of [(18)F]Bombesin and [(11)C]CHO was randomized. Image analysis was performed using summed images as well as dynamic data. To calculate static and dynamic tumor-to-muscle (T/M), tumor-to-blood (T/B), liver-to-blood (L/B), and kidney-to-blood (K/B) ratios, 4 × 4 × 4 mm(3) volumes of interest (VOIs) of tumor, muscle (thigh), liver, kidney, and blood derived from transversal slices were used., Results: The mean T/M ratio of [(18)F]Bombesin and [(11)C]CHO was 6.54 ± 2.49 and 1.35 ± 0.30, respectively. The mean T/B ratio was 1.83 ± 0.79 for [(18)F]Bombesin and 0.55 ± 0.10 for [(11)C]CHO. The T/M ratio as well as the T/B ratio for [(18)F]Bombesin were significantly higher compared to those for [(11)C]CHO (p < 0.001, respectively). Kidney and liver uptake was statistically significantly lower for [(18)F]Bombesin (K/B 3.41 ± 0.81, L/B 1.99 ± 0.38) compared to [(11)C]CHO [K/B 7.91 ± 1.85 (p < 0.001), L/B 6.27 ± 1.99 (p < 0.001)]. The magnitudes of the time course of T/M and T/B ratios (T/M and T/Bdyn ratios) were statistically significantly different (showing a higher uptake of [(18)F]Bombesin compared to [(11)C]CHO); additionally, also the change of the T/M and T/B ratios over time was significantly different between both tracers in the dynamic analysis (p < 0.001, respectively). Furthermore, there was a statistically significantly different change of the K/B and L/B ratios over time between the two tracers in the dynamic analysis (p = 0.026 and p < 0.001, respectively)., Conclusions: [(18)F]Bombesin (BAY 86-4367) visually and semi-quantitatively outperforms [(11)C]CHO in the PC-3 prostate cancer xenograft model. [(18)F]Bombesin tumor uptake was significantly higher compared to [(11)C]CHO. [(18)F]Bombesin showed better imaging properties compared to the clinically utilized [(11)C]CHO due to a higher tumor uptake as well as a lower liver and kidney uptake.

Background/aims: To date, several positron emission tomography/computed tomography (PET/CT) radiotracers including fluorine-18 fluorodeoxyglucose (18F-FDG), carbon-11 labeled choline (11C-choline), 18-F fluorocholine (18F-FCH) and carbon-11 acetate (11C-acetate) have already been assessed in the application of prostate cancer (PCa) diagnosis to some extent, the diagnostic efficiency of these radiotracers still remain controversial. As a result of this, we carried out this meta-analysis for the purpose of comparing the diagnostic accuracy among four PET/CT radiotracers., Methods: A systematical literature search for articles was performed until July 3, 2015. We implemented all analysis using the statistical software of STATA12 and quality assessment was performed using QUADAS-2., Results: A total of 56 studies containing 3,586 patients were included in this meta-analysis. Parameter estimates of the overall analysis are as follows: sensitivity, 0.80 (95% CI: 0.74-0.85); specificity, 0.84 (95% CI: 0.77-0.89) and area under roc curve-AUC of SROC, 0.89 (95% CI: 0.86-0.91), indicating a relatively high level of accuracy in diagnosis of PCa. When different radiotracers of PET/CT were compared, 18F-FCH-PET/CT was ranked as the most favorable with the highest value of AUC (AUC = 0.94; 95% CI: 0.92-0.96) whereas 18F-FDG was the least favorable (AUC = 0.73, 95% CI: 0.69-0.77)., Conclusion: This study suggested that PET/CT imaging plays an invaluable role in the diagnosis of PCa and 18F-FCH-PET/CT was considered as a superior diagnostic tool over other radiotracers. More attention should be paid to the diagnostic efficiency of the four radiotracers particularly for PCa patients with different clinical stages., (© 2016 The Author(s) Published by S. Karger AG, Basel.)

Introduction: The present review was conceived for describing the differences in biodistribution and diagnostic performance of two types of (18)F-radiolabeled choline for positron emission tomography (PET) imaging in prostate cancer (PCa), such as fluoromethylcholine (FCH) and fluoroethylcholine (FEC)., Materials and Methods: A collection of published data about two radiopharmaceutical agents was made by using PubMed, Web of Knowledge databases and Trip Database, and then a critical revision was discussed., Results: FCH was injected in 338 and 1164 patients, while FEC was injected in 20 and 139 patients, respectively for basal staging and re-staging. The diagnostic performances of FCH and FEC for the detection of lymph node metastasis before the surgical approach are typically around 50% or less and between 0% and 39%, respectively. Conversely, both the tracers appear useful for the detection of recurrent PCa in case of increase in absolute PSA value or in case of high levels of PSA velocity and PSA doubling time (sensitivity ranged between 42.9% and 96% for FCH and between 62% and 85.7% for FEC)., Conclusions: In according with the available information, FCH appears to be a more appropriate radiocompound as compared to FEC, although more comparative data are mandatory. A well designed and prospective trial for the evaluation of biokinetic data and diagnostic performance of both radiopharmaceutical agents seems essential., Advances in Knowledge and Implication for Patient Care: FCH seems to be an appropriate radiopharmaceutical agent as compared to FEC. Anyway both the radiocompounds are useful in the evaluation of recurrent disease in case of a serial increase in PSA value and their performance improves when a correct preparation and acquisition protocol is employed., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Given study was aimed to research a role of kinetic performance of PSA in selection of the patients for conduction 11C-choline PET/CT in order to reveal local recurrences in patient with prostate cancer after radiation therapy (RT) and radical prostatectomy (RP). The study included 185 patients with histologically distinctive prostate cancer and biochemical signs of tumor recurrence after RP (61 patients) or RT (124 patients). All the patients were examined using 11C-choline PET/CT in order to detect local relapses. Calculation of growth rate of the PSA level and PSA doubling time were made. According to results of 11C-choline PET/CT, recurrences of prostate cancer were detected in 124 out of 185 (65%). There were 22 patients out of 61 (36%) after RP and there were 102 patients out of 124 (82%) after RT. It was stated a correlation between PSA rates, growth rate of PSA level and presence or absence of relapse according to PET/CT results. PSA level and growth rate of PSA were indicated as the most significant predictive signs, which could influence on the selection of the patients for conduction of 11C-choline PET/CT in relation to detection of local recurrence after RT and RP.

PET/CT with choline is a diagnostic tool useful for imaging prostate cancer patients. The overall published papers in this field are referred to three variants of the same radiopharmaceutical: 11C-Choline, 18FMethylcholine and 18F-Ethylcholine. As no data has been reported on the theoretical differences between these three variants of radiolabeled choline, this study aims to explore the knowledge on the physiological distribution of these three tracers, to compare data of imaging acquisition protocols and to verify the theoretical equivalence in terms of diagnostic accuracy and potential false positive cases that can occur in clinical practice. A literature research about published papers was conducted regarding the physiological distribution, imaging acquisition protocols and diagnostic performance of 11C-choline, 18F-methylcholine and 18F-ethylcholine PET/CT. Minimal differences of the "in vivo" bio-distribution of the variants of radiolabeled choline were registered. Several imaging acquisition protocols were utilized, considering the different half-decay of 11C and 18F and the early urinary excretion of 18F-FECH. The diagnostic accuracy resulted similar for all the tracers, despite an insignificant amount of data for 18F-FECH; however, some pitfalls were documented for all the variants, related to the intrinsic properties of choline as a non-tumour specific tracer. Finally, our clinical experience with the two fluorinated kinds of choline has also been reported describing the "in vivo" bio-distribution with semi-quantitative measurement of Standardised Uptake Value in target organs. The literature suggests these three variants of choline equally useful to be considered for prostate cancer imaging. A standardisation of acquisition protocols for fluorinated choline PET/CT has also been proposed.

We report the results of whole body 18F-fluorocholine (FCH) PET/CT in a single patient with biochemical suspicion of prostate adenocarcinoma relapse and recent history of minor head injury. PET showed an intense area of increased FCH uptake in the right parietal bone, without any morphological abnormality on either CT or skull radiographs. Understanding the radiotracer's physiological biodistribution as well as the nonmalignant etiologies of FCH uptake are essential requirements for a correct diagnostic interpretation of FCH PET/CT in patients with biological recurrence of prostate cancer.

We report a case of a 75-year-old male patient treated with radiotherapy in 1999 for prostate cancer. Due to a rise in prostate-specific antigen, he underwent (11)C-choline PET/CT. The study was negative for secondary lesions but revealed an incidental pathologic focal brain uptake. A subsequent magnetic resonance examination confirmed the presence of a brain lesion typical for meningioma.

Prostate cancer (PCA) is the second most common tumour in men worldwide. Whereas prostate specific antigen (PSA) is an established biochemical marker, the optimal imaging method for all clinical scenarios has not yet been found. With the rising number of PET centres there is an increasing availability and use of (18)F-/(11)C-choline or (11)C-acetate for staging of PCA. However, to date no final conclusion has been reached as to whether acetate or choline tracers should be preferred. In this review we provide an overview of the performance of choline and acetate PET for staging the primary and recurrent disease and lymph nodes in PCA, based on the literature of the last 10 years. Although predominantly choline has been used rather than acetate, both tracers performed in a similar manner in published studies. Choline as well as acetate have insufficient diagnostic accuracy for the staging of the primary tumour, due to a minimum detectable tumour size of 5 mm and inability to differentiate PCA from benign prostate hyperplasia, chronic prostatitis and high-grade intraepithelial neoplasia. Regarding lymph node staging, choline tracers have demonstrated a high specificity. Unfortunately, the sensitivity is only moderate. For staging recurrent disease, sensitivity depends on the level of serum PSA (PSA should be >2 ng/ml). This applies to both choline and acetate. However, despite these limitations, a significant number of patients with recurrent disease can benefit from PET imaging by a change in treatment planning.

Unlabelled: The AIM of this study was to determine whether [¹¹C]choline can be used for docetaxel therapy response assessment in a LNCaP-prostate cancer xenograft mouse model using [¹¹C]choline small-animal PET/CT., Animals, Methods: The androgen-dependent human prostate cancer cell line LNCaP was implanted subcutaneously into the left flanks of 17 SCID-mice, 12.5 mg testosterone platelets were implanted in the neck wrinkle. All mice were injected 4-6 weeks after xenograft implantation with 37 MBq [¹¹C]choline via the tail vein. Dynamic imaging was performed for 60 minutes with a small-animal PET/CT scanner. After the first [¹¹C]choline PET/CT imaging 8 mice were subsequently injected intravenously with docetaxel twice (days 1 and 5) at a dose of 3 mg/kg body weight. 8 mice were treated with PBS as a control. [¹¹C]choline PET/CT imaging was performed on day 7, 14 and 21 after treatment. Image analysis was performed using tumor/muscle (T/M) ratios (ROI(T)/ROI(M) = T/M ratio)., Results: All LNCaP tumours could be visualized by [¹¹C]choline PET/CT. Before treatment the mean T/M ratio was 2.0 ± 0.2 in the docetaxel-treated group and 1.9 ± 0.2 in the control group (p = 0.837). There was a reduction in the mean [¹¹C]choline uptake after docetaxel treatment of the tumours of the LNCaP cell line as early as 1 week after initiation of therapy (T/M(mean) ratio 1.5 ± 0.2 after one week, 1.3 ± 0.2 after 2 weeks and 1.4 ± 0.2 after 3 weeks). There was no decrease in [¹¹C]choline uptake in the control group., Conclusion: Our results show that [¹¹C]choline has the potential for use in the early monitoring of the therapeutic effect of docetaxel in a LNCaP prostate cancer xenograft animal model.

Purpose: To investigate the additional value of (11)C-choline positron emission tomography (PET)-computed tomography (CT) to T2-weighted (T2w) magnetic resonance imaging (MRI) for localization of intraprostatic tumor nodules., Methods and Materials: Forty-nine prostate cancer patients underwent T2w MRI and (11)C-choline PET-CT before radical prostatectomy and extended lymphadenectomy. Tumor regions were outlined on the whole-mount histopathology sections and on the T2w MR images. Tumor localization was recorded in the basal, middle, and apical part of the prostate by means of an octant grid. To analyze (11)C-choline PET-CT images, the same grid was used to calculate the standardized uptake values (SUV) per octant, after rigid registration with the T2w MR images for anatomic reference., Results: In total, 1,176 octants were analyzed. Sensitivity, specificity, and accuracy of T2w MRI were 33.5%, 94.6%, and 70.2%, respectively. For (11)C-choline PET-CT, the mean SUV(max) of malignant octants was significantly higher than the mean SUV(max) of benign octants (3.69 ± 1.29 vs. 3.06 ± 0.97, p < 0.0001) which was also true for mean SUV(mean) values (2.39 ± 0.77 vs. 1.94 ± 0.61, p < 0.0001). A positive correlation was observed between SUV(mean) and absolute tumor volume (Spearman r = 0.3003, p = 0.0362). No correlation was found between SUVs and prostate-specific antigen, T-stage or Gleason score. The highest accuracy (61.1%) was obtained with a SUV(max) cutoff of 2.70, resulting in a sensitivity of 77.4% and a specificity of 44.9%. When both modalities were combined (PET-CT or MRI positive), sensitivity levels increased as a function of SUV(max) but at the cost of specificity. When only considering suspect octants on (11)C-choline PET-CT (SUV(max) ≥ 2.70) and T2w MRI, 84.7% of these segments were in agreement with the gold standard, compared with 80.5% for T2w MRI alone., Conclusions: The additional value of (11)C-choline PET-CT next to T2w MRI in detecting tumor nodules within the prostate is limited., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Unlabelled: PET with (18)F-choline ((18)F-FCH) is used in the diagnosis of prostate cancer and its recurrences. In this work, biodistribution data from a recent study conducted at Skåne University Hospital Malmö were used for the development of a biokinetic and dosimetric model., Methods: The biodistribution of (18)F-FCH was followed for 10 patients using PET up to 4 h after administration. Activity concentrations in blood and urine samples were also determined. A compartmental model structure was developed, and values of the model parameters were obtained for each single patient and for a reference patient using a population kinetic approach. Radiation doses to the organs were determined using computational (voxel) phantoms for the determination of the S factors., Results: The model structure consists of a central exchange compartment (blood), 2 compartments each for the liver and kidneys, 1 for spleen, 1 for urinary bladder, and 1 generic compartment accounting for the remaining material. The model can successfully describe the individual patients' data. The parameters showing the greatest interindividual variations are the blood volume (the clearance process is rapid, and early blood data are not available for several patients) and the transfer out from liver (the physical half-life of (18)F is too short to follow this long-term process with the necessary accuracy). The organs receiving the highest doses are the kidneys (reference patient, 0.079 mGy/MBq; individual values, 0.033-0.105 mGy/MBq) and the liver (reference patient, 0.062 mGy/MBq; individual values, 0.036-0.082 mGy/MBq). The dose to the urinary bladder wall of the reference patient varies between 0.017 and 0.030 mGy/MBq, depending on the assumptions on bladder voiding., Conclusion: The model gives a satisfactory description of the biodistribution of (18)F-FCH and realistic estimates of the radiation dose received by the patients.

Background: Positron emission tomography (PET or combined PET-computed tomography (PET/CT)) allows the non-invasive interrogation of metabolic processes using radiolabeled probes. Altered choline metabolism has been noted as a characteristic of prostate cancer (PCa), and radiolabeled choline and choline analogs have been investigated as PET/CT imaging agents for prostate cancer; [(18)F]fluoromethyl-dimethyl-2-hydroxyethyl-ammonium ((18)F-FCH) shows particular promise as a PCa imaging agent given its favorable physical and pharmacokinetic properties., Methods: We conducted a systematic review of results to date with (18)F-FCH. As the tracer was first described by DeGrado in 2001, we limited our search from January 2001 to August 2011., Results: In all, 37 studies including 1244 patients met the inclusion criteria. Studies included those detailing the radiosynthesis of (18)F-FCH, preclinical and early clinical dosimetry, and biodistribution (n=7); evaluation of local disease (n=6), nodal disease (n=5), bone metastases and castrate-resistant disease (n=7), biochemical recurrence (n=11), radiotherapy planning (n=7) and sources of false-positive studies (n=2); and some studies reported on multiple indications. Potential sources of variations in the studies affecting reported performance included case series size, variation in extent of disease at imaging (including Gleason grade, and PSA), selection of gold standards for comparison and variations in scan technique., Conclusions: On the basis of the review, we suggest potential scenarios where this metabolic imaging might be considered for further evaluation in clinical trials for guiding PCa management.

Introduction: This work develops a compartmental model of (18)F-choline in order to evaluate its biokinetics and so to describe the temporal variation of the radiopharmaceuticals' uptake in and clearance from organs and tissues., Methods: Ten patients were considered in this study. A commercially available tool for compartmental analysis (SAAM II) was used to model the values of activity concentrations in organs and tissues obtained from PET images or from measurements of collected blood and urine samples., Results: A linear compartmental model of the biokinetics of the radiopharmaceutical was initially developed. It features a central compartment (blood) exchanging with organs. The structure describes explicitly liver, kidneys, spleen, blood and urinary excretion. The linear model tended to overestimate systematically the activity in the liver and in the kidney compartments in the first 20 min post-administration. A nonlinear process of kinetic saturation was considered, according to the typical Michaelis-Menten kinetics. Therefore nonlinear equations were added to describe the flux of (18)F-choline from blood to liver and from blood to kidneys. The nonlinear model showed a tendency for improvement in the description of the activity in liver and kidneys, but not for the urine., Conclusions: The simple linear model presented is not able to properly describe the biokinetics of (18)F-choline as measured in prostatic cancer patients. The introduction of nonlinear kinetics, although based on physiologically plausible assumptions, resulted in nonsignificant improvements of the model predictive power., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the accuracy and biological basis for [(11)C]choline-PET-CT in the nodal staging of high risk localized prostate cancer patients., Experimental Design: Twenty-eight patients underwent dynamic [(11)C]choline-PET-CT of the pelvis and lower abdomen prior to extended laparoscopic pelvic lymph node dissection (eLPL). The sensitivity and specificity of [(11)C]choline PET, [(11)C]choline PET-CT, and MRI for nodal detection were calculated. Average and maximal standardized uptake values (SUV(ave), SUV(max)) were compared with choline kinase alpha (CHKα) and Ki67 immunohistochemistry scores., Results: Four hundred and six lymph nodes (LN), in 26 patients, were assessable. Twenty-seven (6.7%) involved pelvic nodes at eLPL were detected in 9 patients. Seventeen of the 27 involved nodes were subcentimeter. The sensitivity and specificity on a per nodal basis were 18.5% and 98.7%, 40.7% and 98.4%, and 51.9% and 98.4% for MRI, [(11)C]choline PET, and [(11)C]choline PET-CT, respectively. Sensitivity was higher for [(11)C]choline PET-CT compared with MRI (P = 0.007). A higher nodal detection rate, including subcentimeter nodes, was seen with [(11)C]choline PET-CT than MRI. Malignant lesions showed CHKα expression in both cytoplasm and nucleus. SUV(ave) and SUV(max) strongly correlated with CHKα staining intensity (r = 0.68, P < 0.0001 and r = 0.63, P = 0.0004, respectively). In contrast, Ki67 expression was generally low in all tumors., Conclusion: This study establishes the relationship between [(11)C]choline PET-CT uptake with choline kinase expression in prostate cancer and allows it to be used as a noninvasive means of staging pelvic LNs, being highly specific and more sensitive than MRI, including the detection of subcentimeter disease., (©2011 AACR.)

Summary: Fluorine-18-methyl-choline (F18-choline) PET/computed tomography (CT) is routinely performed in our hospital for patients with significantly increased or rapidly increasing prostate-specific antigen (PSA) levels to detect and localize recurrent prostate carcinoma. We observed uptake of this PET tracer in mediastinal lymph nodes in a significant number of patients. The aim of this study was to assess the frequency of this finding and to determine whether it is correlated with tumour and nontumour-related aspects., Materials and Methods: A total of 48 consecutive men (mean age: 65.6 years; range: 50-79 years, standard deviation: 7.1) with histopathologically proven prostate cancer were referred for F18-choline PET/CT imaging for restaging from March 2009 to October 2010. All patients had a suspicion of tumour recurrence because of an increased PSA or a rapidly increasing PSA. All studies were reviewed, and the results were correlated with general data such as age; smoking; chronic obstructive pulmonary disease; tumor, lymph nodes and distant metastases stage; Gleason Score and PSA level; with a maximum interval of 3 months between serum PSA and the PET/CT scan., Results: In 27 patients (56.3%), F18-choline PET/CT showed positive lymph nodes in the mediastinum (mean standardized uptake values: 3.75; range: 1.7-13.8, standard deviation: 2.4). No histological biopsy was carried out in F18-choline-positive lymph nodes, but in none of the patients was mediastinal recurrence or pulmonary infection observed during a 6-month follow-up. Only one patient had histologically proven pulmonary metastasis. No significant relationship was observed between mediastinal F18-choline lymph node uptake and serum PSA level (P=0.785), initial T stage (P=0.555), N stage (P=0.548), M stage (P=0.426), smoking (P=0.537), chronic obstructive pulmonary disease (P=0.115) or the presence of tumour recurrence on F18-choline PET/CT., Conclusion: Mediastinal lymph node uptake of F18 choline is frequently observed, without any significant relationship with tumour characteristics. Therefore, interpretation of positive mediastinal lymph node uptake should be done carefully.

Unlabelled: The pharmacokinetics of (18)F-fluorodeoxythymidine (FLT), (18)F-FDG, (11)C-choline, and (18)F-fluoroethylcholine (FEC) in 2 hormone-independent (PC-3, DU145) and 2 hormone-dependent (CWR22, PAC120) prostate cancer xenograft mouse models were evaluated by PET and compared by immunohistochemistry. Further investigation was performed to determine whether PET can detect early changes in tumor metabolism after androgen ablation therapy through surgical castration., Methods: PET was performed on 4 consecutive days. In addition, the CWR22 and PAC120 tumor models were surgically castrated after the baseline measurement and imaged again after castration. The tracer uptake was analyzed using time-activity curves, percentage injected dose per volume (%ID/cm(3)), and tumor-to-muscle ratio (T/M)., Results: Regarding the hormone-independent prostate tumor models, (18)F-FLT showed the best T/M and highest %ID/cm(3) in PC-3 (2.97 ± 0.63 %ID/cm(3)) and DU145 (2.06 ± 0.75 %ID/cm(3)) tumors. (18)F-FDG seemed to be the tracer of choice for delineation of the PC-3 tumors but not for the DU145 tumors. Using (11)C-choline (PC-3: 1.33 ± 0.29 %ID/cm(3), DU145: 1.60 ± 0.27 %ID/cm(3)) and (18)F-FEC, we did not find any significant uptake in the tumors, compared with muscle tissue. Regarding the hormone-dependent prostate tumor models, the CWR22 model showed a highly significant (P < 0.01) decrease in tumor (18)F-FDG uptake from 4.11 ± 1.29 %ID/cm(3) to 2.19 ± 1.45 %ID/cm(3) after androgen ablation therapy. However, the (18)F-FLT, (11)C-choline, or (18)F-FEC tracers did not provide sufficient uptake or reliable information about therapy response in CWR22 tumors. The PAC120 model showed a significant increase in (18)F-FLT tumor uptake (P = 0.015) after androgen ablation therapy. The accumulation of (18)F-FEC (before: 2.32 ± 1.01 %ID/cm(3), after: 1.36 ± 0.39 %ID/cm(3)) was found to be the next highest after (18)F-FDG (before: 2.45 ± 0.93 %ID/cm(3), after: 2.18 ± 0.65 %ID/cm(3)) in PAC120 tumors before castration and is better suited for monitoring therapy response., Conclusion: This comprehensive study in 2 hormone-dependent and 2 hormone-independent prostate tumor mouse models shows that (18)F-FLT and (18)F-FDG are the most appropriate tracers for delineation of PC-3, DU145 (except (18)F-FDG), and CWR22 tumors, but not for PAC120 tumors. (18)F-FEC and (11)C-choline, in particular, revealed insufficient T/M ratio in the prostate tumor models. The results may indicate that radiolabeled choline and choline derivatives compete with a high concentration of the precursor dimethylaminoethanol, resulting in reduced uptake in small-rodent tumor models, a hypothesis that is currently under investigation in our laboratory.

Purpose: Prostate cancer (PC) is a major health problem. Overexpression of the gastrin-releasing peptide receptor (GRPR) in PC, but not in the hyperplastic prostate, provides a promising target for staging and monitoring of PC. Based on the assumption that cancer cells have increased metabolic activity, metabolism-based tracers are also being used for PC imaging. We compared GRPR-based targeting using the (68)Ga-labelled bombesin analogue AMBA with metabolism-based targeting using (18)F-methylcholine ((18)F-FCH) in nude mice bearing human prostate VCaP xenografts., Methods: PET and biodistribution studies were performed with both (68)Ga-AMBA and (18)F-FCH in all VCaP tumour-bearing mice, with PC-3 tumour-bearing mice as reference. Scanning started immediately after injection. Dynamic PET scans were reconstructed and analysed quantitatively. Biodistribution of tracers and tissue uptake was expressed as percent of injected dose per gram tissue (%ID/g)., Results: All tumours were clearly visualized using (68)Ga-AMBA. (18)F-FCH showed significantly less contrast due to poor tumour-to-background ratios. Quantitative PET analyses showed fast tumour uptake and high retention for both tracers. VCaP tumour uptake values determined from PET at steady-state were 6.7 ± 1.4%ID/g (20-30 min after injection, N = 8) for (68)Ga-AMBA and 1.6 ± 0.5%ID/g (10-20 min after injection, N = 8) for (18)F-FCH, which were significantly different (p <0.001). The results in PC-3 tumour-bearing mice were comparable. Biodistribution data were in accordance with the PET results showing VCaP tumour uptake values of 9.5 ± 4.8%ID/g (N = 8) for (68)Ga-AMBA and 2.1 ± 0.4%ID/g (N = 8) for (18)F-FCH. Apart from the GRPR-expressing organs, uptake in all organs was lower for (68)Ga-AMBA than for (18)F-FCH., Conclusion: Tumour uptake of (68)Ga-AMBA was higher while overall background activity was lower than observed for (18)F-FCH in the same PC-bearing mice. These results suggest that peptide receptor-based targeting using the bombesin analogue AMBA is superior to metabolism-based targeting using choline for scintigraphy of PC.

Purpose: (11)C-Choline-positron emission tomography (PET)/computed tomography (CT) is increasingly used in patients with prostate cancer. Another promising technique for assessment of tumor biology is diffusion-weighted MR imaging (DWI). The aim of the study was to compare the functional parameters standardized uptake value (SUV) in PET and apparent diffusion coefficient (ADC) value in DWI of lymph nodes in prostate cancer patients., Procedures: Fourteen patients with prostate cancer underwent DWI at 1.5T and (11)C-Choline-PET/CT. ADC values and SUVs of all lymph nodes larger than 5 mm (n = 55) were compared by using linear regression analysis. Performance of DWI and (11)C-Choline PET was assessed by receiver operator characteristic curve analysis using histopathology or clinical follow-up as standard of reference., Results: ADC values and SUV showed a moderate but highly significant inverse correlation (r = -0.5144, p < 0.0001). In lymph nodes with low ADC values, the dispersion of SUV was more pronounced. Moreover, a highly significant difference was observed for mean ADC values and SUV in lymph nodes considered as benign or malignant by follow-up/histopathology (ADC 1.60 ± 0.24 vs. 1.09 ± 0.23 × 10(-3) mm(2)/s; SUV 1.82 ± 0.57 vs. 4.68 ± 03.12; p < 0.0001, respectively)., Conclusion: These pilot data propose the ADC value in DWI as a new potential imaging biomarker which might provide additional information on tumor pathophysiology compared to the SUV in (11)C-Choline PET/CT.

Biokinetic data are important when calculating the absorbed dose to the patients and can also be used to find the optimal time between injection and imaging. To the authors' knowledge, there are no published biokinetic data in humans for (18)F-choline, except some distribution data at single time points. Four patients with suspicion of metastases due to biochemical recurrence (measurable prostate-specific antigen in plasma) after radical prostatectomy were injected with (18)F-choline. Four whole-body PET/CT images were taken with 1 h interval, starting immediately after injection. Blood samples were taken and all urine was collected for 3.5 h. The corrected decay activity content in the kidneys was 22-37 % higher immediately after injection when compared with the later time points. The highest activity concentration was found in kidneys (43 kBq ml(-1)). The organ with highest activity content was the liver (11 % of injected activity, % IA). Thirty minutes after the injection 4-16 % IA was left in the blood. Less than 9 % IA was excreted with the urine during the first 3.5 h after injection.

Objectives: 18F-choline positron emission tomography (PET)/computed tomography (CT) is an integral part in restaging of patients with prostate cancer (PC). The aim of this study was to describe the whole-body physiologic distribution of 18F-choline and to discuss some abnormal sites of uptake not related to PC we observed., Materials and Methods: Eighty consecutive patients submitted to 18F-choline PET/CT imaging for primary staging or biochemical recurrence (prostate specific antigen rising) after treatment of PC was considered. Whole-body PET/CT was acquired approximately 40 min after 18F-choline injection., Results: We observed physiological 18F-choline uptake in liver, pancreas, spleen, salivary and lachrymal glands and also, owing to renal excretion, in urinary tract. Other sites of less intense tracer uptake were bone marrow and intestines. We found abnormal and unexpected PET findings in 15 patients (18.7%), not owing to PC localizations. The majority of these findings were owing to inflammation (12 of 15); a case of low grade lymphoma was detected; two patients showed focal brain uptake of 18F-choline and were subsequently submitted to magnetic resonance: in one a meningioma and in the other a low-grade brain tumour were diagnosed., Conclusion: Accurate knowledge of the biodistribution of 18F-choline is essential for the correct interpretation of PET/CT imaging. CT enables differentiation of physiological bowel activity and 18F-choline excretion in the ureters. In our series, 18F-choline uptake in benign pathological conditions mainly included sites of inflammation; nevertheless, accumulation in tumour deposits not because PC cannot be excluded, particularly in the brain, where correlative imaging with magnetic resonance is of the utmost importance.

Purpose: Choline derivatives labelled with positron emitters are successfully used for PET imaging of prostate cancer patients. Since little is known about uptake mechanisms, the aim of this study was to characterize choline uptake in prostate cancer cells, also following anti-androgen treatment or chemotherapy., Methods: Choline uptake in prostate cancer cells (LNCaP, PC-3) and Michaelis-Menten kinetics were analysed using different concentrations of (3)H-choline via liquid scintillation counting. Inhibition of (3)H-choline uptake was assayed in the presence of hemicholinium-3 (HC-3), unlabelled choline, guanidine and tetraethylammonium (TEA), an inhibitor of the organic cation transporter (OCT). Changes in choline uptake triggered by bicalutamide and docetaxel were evaluated and choline transporters were detected via Western blotting., Results: Michaelis-Menten kinetics yielded a saturable transport with K(m) values of 6.9 and 7.0 micromol/l choline for LNCaP and PC-3 cells, respectively. Treatment of cells with bicalutamide and docetaxel caused an increase in total choline uptake but had no significant effect on K(m) values. Uptake of (3)H-choline was NaCl dependent and 4.5-fold higher in LNCaP cells than in PC-3 cells. (3)H-Choline uptake was reduced by 92-96% using HC-3 and unlabelled choline, by 63-69% using guanidine and by 20% using TEA. The high-affinity choline transporter was detected via Western blotting., Conclusion: Choline uptake in prostate cancer cells is accomplished both by a transporter-mediated and a diffusion-like component. Results of inhibition experiments suggest that uptake is mediated by a selective choline transporter rather than by the OCT. Bicalutamide- and docetaxel-induced changes in total choline uptake could affect PET tumour imaging.

Unlabelled: The purpose of this study was to investigate the effect of total prostate-specific antigen (PSA) at the time of (11)C-choline PET/CT (trigger PSA), PSA velocity (PSAvel), and PSA doubling time (PSAdt) on (11)C-choline PET/CT detection rate in patients treated with radical prostatectomy for prostate cancer, who showed biochemical failure during follow-up., Methods: A total of 190 patients treated with radical prostatectomy for prostate cancer who showed an increase in PSA (mean, 4.2; median, 2.1; range, 0.2-25.4 ng/mL) were retrospectively enrolled. All patients were studied with (11)C-choline PET/CT. Patients were grouped according to trigger PSA (PSA 5 ng/mL). In 106 patients, data were available for calculation of PSAvel and PSAdt. Logistic regression analysis was used to determine whether there was a relationship between PSA levels and PSA kinetics and the rate of detection of relapse using PET., Results: (11)C-choline PET/CT detected disease relapse in 74 of 190 patients (38.9%). The detection rate of (11)C-choline PET/CT was 19%, 25%, 41%, and 67% in the 4 subgroups-PSA 5 ng/mL (49 patients)-respectively. Trigger PSA values were statistically different between PET-positive patients (median PSA, 4.0 ng/mL) and PET-negative patients (median PSA, 1.4 ng/mL) (P = 0.0001). Receiver-operating-characteristic analysis showed an optimal cutoff point for trigger PSA of 2.43 ng/mL (area under the curve, 0.76). In 106 patients, PSAdt and PSAvel values were statistically different between patients with PET-positive and -negative scan findings (P = 0.04 and P = 0.03). The (11)C-choline PET/CT detection rate was 12%, 34%, 42%, and 70%, respectively, in patients with PSAvel < 1 ng/mL/y (33 patients), 1 < PSAvel 5 ng/mL/y (28 patients). The (11)C-choline PET/CT detection rate was 20%, 40%, 48%, and 60%, respectively, in patients with PSAdt > 6 mo (45 patients), 4 < PSAdt

Objective: To compare the diagnostic accuracy of PET/CT with (18)F-FDG and (11)C-choline for early detection and localization of recurrent prostate cancer., Material and Methods: Thirty-eight patients with increased PSA levels (0.8-9.5 ng/ml) after radical treatment for prostate cancer (surgery n = 20/radiation therapy n = 18) were included. Ten patients were on hormone therapy. All patients underwent a PET/CT with (11)C-choline and (18)F-FDG, respectively, on the same day. The PET imaging findings were compared with histopathology (n = 10); PSA monitoring (n = 21) and/ or other methods (n = 7)., Results: Focal uptake of (11)C-choline was detected in 26 patients (68%), and focal uptake of (18)F-FDG was detected in 13 patients (34%). The (11)C-choline uptake in 14 patients was suggested local recurrence, whereas this was true in only 4 patients (48%) with (18)F-FDG. Pelvic lymph nodes were detected with (11)C-choline PET/CT in 8 patients and only in 4 patients (50%) with (18)F-FDG. Mediastinal involvement was detected in 5 patients with (11)C-choline and 3 patients (60%) with (18)F-FDG. Focal bone involvement was detected in 3 patients with (11)C-choline and (18)F-FDG. (11)C-choline was able to detect 40% of recurrences in patients with PSA < 1 ng/ml, 50% of recurrences in patients with PSA 1-4 ng/ml and 87% of recurrences with PSA > 4 ng/ml. Sensitivity of (11)C-choline was higher for surgically treated patients, with no significant differences found between patients with and without hormone therapy., Conclusions: (11)C-choline PET/CT was useful for the detection of biochemical recurrence of prostate cancer, with higher yielding as compared to (18)F-FDG. (11)C-choline sensitivity was clearly related to PSA levels, was higher in patients with surgery and did not seem to be modified by hormonal therapy. Disease staging with (11)C-choline showed direct impact for the selection of the most appropriate therapeutic approach.

Purpose: The accuracy of positron emission tomography (PET)/CT with [(11)C]choline for the detection of prostate cancer is not well established. We assessed the dependence of [(11)C]choline maximum standardized uptake values (SUV(max)) in the prostate gland on cell malignancy, prostate-specific antigen (PSA) levels, Gleason score, tumour stage and anti-androgenic hormonal therapy., Methods: In this prospective study, PET/CT with [(11)C]choline was performed in 19 prostate cancer patients who subsequently underwent prostatectomy with histologic sextant analysis (group A) and in six prostate cancer patients before and after anti-androgenic hormonal therapy (bicalutamide 150 mg/day; median treatment of 4 months; group B)., Results: In group A, based on a sextant analysis with a [(11)C]choline SUV(max) cutoff of 2.5 (as derived from a receiver-operating characteristic analysis), PET/CT showed sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 72, 43, 64, 51 and 60%, respectively. In the patient-by-patient analysis, no significant correlation was detected between SUV(max) and PSA levels, Gleason score or pathological stage. On the contrary, a significant (P < 0.05) negative correlation was detected between SUV(max) and anti-androgenic therapy both in univariate (r (2) = 0.24) and multivariate (r (2) = 0.48) analyses. Prostate [(11)C]choline uptake after bicalutamide therapy significantly (P < 0.05) decreased compared to baseline (6.4 +/- 4.6 and 11.8 +/- 5.3, respectively; group B)., Conclusion: PET/CT with [(11)C]choline is not suitable for the initial diagnosis and local staging of prostate cancer. PET/CT with [(11)C]choline could be used to monitor the response to anti-androgenic therapy.

Background and Purpose: Choline positron emission tomography (PET) can help to optimize radiation treatment strategy of prostate cancer. Therefore, the aim of this study was to elucidate the effects of ionizing radiation on the choline uptake in an androgen-dependent (LNCaP) and an androgen-independent (PC3) prostate cancer cell line., Material and Methods: Uptake of [methyl-(3)H]choline chloride was investigated between 4 and 96 h after irradiation with 6 Gy. Dose dependence of choline uptake was examined following irradiation with 2-12 Gy, and cell survival was analyzed via the clonogenic assay. Michaelis-Menten kinetics was determined 24 h (PC3) and 48 h (LNCaP) after irradiation with 6 Gy., Results: PC3 cells showed a significant transitory increase of [methyl-(3)H]choline uptake with a maximum at 24 h after irradiation. In LNCaP cells irradiation induced a significant decrease with a minimum at 48 h. Changes in choline uptake in both cell lines were almost dose-independent up to 12 Gy. Following irradiation with 6 Gy, transport capacity (v(max)) increased and Michaelis-Menten constant (K(M)) decreased in PC3 cells, while in LNCaP cells the two parameters behaved vice versa., Conclusion: Changes in choline uptake following irradiation might be due to metabolic changes associated with initiation of processes that finally cause cell death. Thus, changes in tumor choline uptake monitored by PET after radiotherapy might not exclusively reflect therapeutic success but also altered tracer uptake as a consequence of irradiation.

To assess positron emission tomography (PET) with fluorine-18 fluorocholine for sextant localization of malignant prostate tumors. Histopathologic analysis was performed on step-sectioned whole-mounted prostate specimens from 15 patients who underwent PET with fluorocholine prior to radical prostatectomy. The maximum standardized uptake value (SUVmax) corresponding to prostate sextants on PET was measured by region of interest analysis and compared with histopathologic results. Histopathology demonstrated malignant involvement in 61 of 90 prostate sextants. The mean total tumor volume per specimen was 4.9 mL (range 0.01-28.7 mL). Mean SUVmax was 6.0+/-2.0 in malignant sextants and 3.8+/-1.4 in benign sextants (p<.0001). The area under the receiver operating characteristic curve was 0.82 for sextant detection of malignancy based on SUVmax measurement. Tumor diameter directly correlated with sextant SUVmax in malignant sextants (r=.54, p<.05). In 13 subjects, the largest tumor in the specimen corresponded to the sextant with the highest SUVmax. Fluorocholine PET can serve to localize dominant areas of malignancy in patients with prostate cancer. However, PET with fluorocholine may fail to identify sextants with smaller volumes of malignancy.

Introduction: Choline, acetate and glucose ([2-(18)F]fluoro-2-deoxyglucose, [(18)F]FDG) analogs are under investigation as positron emission tomography (PET) tracers for the imaging of prostate cancer; however, their response to tumor hypoxia has not been clarified., Methods: The uptake of [methyl-(3)H]choline, [1-(14)C]acetate and [(18)F]FDG was monitored in androgen-independent PC-3 cells and androgen-sensitive LNCaP cells under aerobic or anoxic conditions. The effect of androgen depletion was also examined., Results: PC-3 cells exhibited aerobic choline and acetate uptake five to six times higher than FDG uptake, whereas LNCaP cells showed choline uptake 2.2-fold higher than acetate uptake and 10-fold higher than FDG uptake. After 4 h of anoxia, PC-3 cells showed an 85% increase in FDG uptake, a 15% decrease in choline uptake and a 36% increase in acetate uptake, whereas LNCaP cells showed a 212% increase in FDG uptake, a 28% decrease in choline uptake and no change in acetate uptake. Androgen depletion resulted in a marked decrease in the uptake of all tracers in LNCaP cells but no changes in PC-3 cells., Conclusion: In aerobic conditions, both PC-3 and LNCaP cells exhibited an order of uptake preference as follows: choline>acetate>FDG. In hypoxic cells, the order is reversed, reflecting diverse biochemical responses to hypoxia. These findings may help to explain PET imaging findings of the diverse responses of these tracers in different stages and locations of prostate cancer. Androgen depletion markedly suppressed the uptake of all three tracers in LNCaP cells, which suggests the potential for underestimation of the disease state when PET imaging is performed subsequent to antiandrogen therapy.

Purpose: Prostate cancer is the second leading cause of death from cancer among US men. Positron emission tomography (PET) with [(11)C]choline has been shown to be useful in the staging and detection of prostate cancer. The background of the increased uptake of choline in human prostate cancer is not completely understood. The aim of this study was to prospectively investigate the relationship between the [(11)C]choline uptake and the cell proliferation in human prostate cancer., Methods: Prostate cancer tissue from 18 patients who had undergone a radical prostatectomy for histologically proven disease was studied. An [(11)C]choline PET scan was performed prior to surgery. Post-prostatectomy specimens were prepared and stained with the antibody MIB-1 for Ki-67, which depicts proliferation. Two independent observers counted the amount of stained nuclei per specimen., Results: Prostate cancer showed Ki-67 staining and high uptake of [(11)C]choline. Statistical analysis showed no significant correlation between [(11)C]choline uptake and Ki-67 staining (R=0.23; P=0.34). No significant relationships were found between the uptake of [(11)C]choline (SUV) and either preoperative PSA (R=0.14; P=0.55) or Gleason sum score (R=0.28; P=0.25)., Conclusion: In vivo uptake of [(11)C]choline does not correlate with cell proliferation in human prostate cancer as depicted by Ki-67. Our results suggest that a process other than proliferation is responsible for the uptake of [(11)C]choline in prostate cancer.

11C-labeled choline ([11C]CHO) and 18F-fluorinated choline analogues have been demonstrated to be valuable tracers for in vivo imaging of neoplasms by means of positron emission tomography (PET). The objective of the present study was to evaluate whether deshydroxy-[18F]fluorocholine, ([18F]dOC), a non-metabolizable [18F]fluorinated choline analogue, can serve as a surrogate for cholines that are able to be phosphorylated and thus allow PET-imaging solely by addressing the choline transport system. The specificity of uptake of [18F]dOC was compared with that of [11C]choline ([11C]CHO) in cultured rat pancreatic carcinoma and PC-3 human prostate cancer cells in vitro. In addition, biodistribution of [18F]dOC and [11C]CHO was compared in AR42J- and PC-3 tumor bearing mice. The in vitro studies revealed that membrane transport of both compounds can be inhibited in a concentration dependent manner by similar concentrations of cold choline (IC50 [18F]dOC= 11 microM; IC50 [11C]CHO=13 microM. In vitro studies with PC-3 and AR42J cells revealed that the internalized fraction of [18F]dOC after 5 min incubation time is comparable to that of [11C]CHO, whereas the uptake of [11C]CHO was superior after 20 min incubation time. As for [11C]CHO, kidney and liver were also the primary sites of uptake for [18F]dOC in vivo. Biodistribution data after simultaneous injection of both tracers into AR42J tumor bearing mice revealed slightly higher tumor uptake for [18F]dOC at 10 min post-injection, whereas [11C]CHO uptake was higher at later time points. In conclusion, [18F]dOC is taken up into AR42J rat pancreatic carcinoma and PC-3 human prostate cancer cells by a choline specific transport system. Similar transport rates of [18F]dOC and [11C]CHO result in comparable cellular uptake levels at early time points. In contrast to [18F]dOC, which is transported but not intracellularly trapped, the choline kinase substrate [11C]CHO is transported into tumor cells and retained. Thus, the signal obtained by imaging early after injection is mainly reflecting transport, whereas a valid quantification of choline kinase activity needs imaging at later time points. Further studies have to clarify whether quantification of the transport capacity or the choline kinase activity result in a better pathophysiological correlate and thus is the more useful process for tumor characterization.

[(11)C]Choline has been evaluated as a positron emission tomography (PET) biomarker for assessment of established human prostate cancer tumor models. [(11)C]Choline was prepared by the reaction of [(11)C]methyl triflate with 2-dimethylaminoethanol (DMAE) and isolated and purified by solid-phase extraction (SPE) method in 60-85% yield based on [(11)C]CO(2), 15-20 min overall synthesis time from end of bombardment (EOB), 95-99% radiochemical purity and specific activity >0.8 Ci/micromol at end of synthesis (EOS). The biodistribution of [(11)C]choline was determined at 30 min post iv injection in prostate cancer tumor models C4-2, PC-3, CWR22rv, and LNCaP tumor-bearing athymic mice. The results showed the accumulation of [(11)C]choline in these tumors was 1.0% dose/g in C4-2 mouse, 0.4% dose/g in PC-3 mice, 3.2% dose/g in CWR22rv mice, and 1.4% dose/g in LNCaP mice; the ratios of tumor/muscle (T/M) and tumor/blood (T/B) were 2.3 (T/M, C4-2), 1.4 (T/M, PC-3), 2.5 (T/M, CWR22rv), 1.2 (T/M, LNCaP) and 2.6 (T/B, C4-2), 2.6 (T/B, PC-3), 7.8 (T/B, CWR22rv), 3.2 (T/B, LNCaP), respectively. The micro-PET imaging of [(11)C]choline in prostate cancer tumor models was acquired from a C4-2, PC-3, CWR22rv, or LNCaP implanted mouse at 30 min post iv injection of 1 mCi of the tracer using a dedicated high resolution (<3 mm full-width at half-maximum) small FOV (field-of-view) PET imaging system, IndyPET-II scanner, developed in our laboratory, which showed the accumulation of [(11)C]choline in C4-2, PC-3, CWR22rv, or LNCaP tumor implanted in a nude athymic mouse. The initial dynamic micro-PET imaging data indicated the average T/M ratios were approximately 3.0 (C4-2), 2.1 (PC-3), 3.5 (CWR22rv), and 3.3 (LNCaP), respectively, which showed the tumor accumulation of [(11)C]choline in all four tumor models is high. These results suggest that there are significant differences in [(11)C]choline accumulation between these different tumor types, and these differences might offer some useful measure of tumor biological process.

Carbon-11 choline has recently been introduced as a potential tracer for tumour imaging with positron emission tomography (PET). We evaluated the kinetics of the uptake of [(11)C]choline in prostate cancer and benign prostatic hyperplasia. We also evaluated the association between the uptake of [(11)C]choline and the histological grade of malignancy, Gleason score, volume of the prostate and prostate-specific antigen (PSA). Fourteen patients with histologically confirmed prostate cancer and five patients with benign prostatic hyperplasia were studied with [(11)C]choline PET. A mean dose of 430+/-31 MBq of [(11)C]choline was injected intravenously and a dynamic emission acquisition of prostate was performed for 30 min. The uptake of [(11)C]choline was measured as a standardised uptake value (SUV) and as a kinetic influx constant ( K(i)) obtained from graphical analysis. Both cancerous and hyperplastic prostate were well visualised with [(11)C]choline against low or moderate tracer accumulation in the bladder and rectal wall. The measured radioactivity in urine was invariably low. In the graphical analysis, linear plots were achieved. The mean K(i) of the untreated tumour was 0.205+/-0.089 min(-1) (range 0.128-0.351; n=7) and the mean SUV was 5.6+/-3.2 (range 1.9-15.5; n=15). K(i) values and SUVs correlated closely ( r=0.964, P=0.0005), whereas no correlation could be demonstrated between the tumour uptake of [(11)C]choline and the histological grade, Gleason score, volume of the prostate or PSA. The mean SUV and the mean K(i) of benign hyperplastic prostate were 3.5+/-1.0 (range 2.0-4.5; n=4) and 0.119+/-0.076 min(-1) (range 0.065-0.173; n=2). In conclusion, a high uptake of [(11)C]choline characterises not only carcinomatous but also hyperplastic prostatic tissue. Dynamic imaging of the uptake of [(11)C]choline in the prostate shows a good applicability of the graphical analysis model with an irreversible compartment. A close correlation between the K(i) values and semiquantitative SUVs of tumours supports the use of the simpler SUV in the clinical setting.

Purpose: Positron emission tomography (PET) imaging is used for the metabolic evaluation of cancer. [18F]fluorodeoxyglucose (FDG) is commonly used as a radiotracer but its low cellular uptake rate in prostate cancer limits its usefulness. We evaluated the novel choline analog [18F]fluorocholine (FCH) for detecting androgen dependent and androgen independent prostate cancer, and its metastases., Materials and Methods: The cellular uptake of FCH and FDG was compared in cultured prostate cancer cells (LNCaP and PC-3). FCH and FDG were injected into nude mice xenografts (CWR-22 and PC-3) and radiotracer uptake in various organs were evaluated. Patients with androgen dependent (9) and independent (9) prostate cancer were studied by FCH and FDG PET., Results: FCH uptake was 849% and 60% greater than FDG uptake in androgen dependent (LNCaP) and independent (PC-3) cells, respectively. The addition of hemicholinium-3 (5 mM.) 30 minutes before radiotracer administration inhibited FCH uptake by 79% and 70% in LNCaP and PC-3 cells, respectively, whereas FDG uptake was not significantly affected. Although nude mice xenografts showed that FDG uptake was equal to or greater than FCH uptake, clinical imaging in patients demonstrated 2 to 4-fold higher uptake of FCH in those with androgen and androgen independent prostate carcinoma (p <0.001). More lesions were detected by FCH than by FDG in primary tumors, osseous metastases and soft tissue metastases., Conclusions: In vitro data demonstrated greater FCH than FDG uptake in androgen dependent (LNCaP) and androgen independent (PC-3) prostate cancer cells. Although the murine xenograft data showed greater accumulation of FDG than FCH in PC-3 tumors, PET in humans showed that FCH was better than FDG for detecting primary and metastatic prostate cancer. Overall the data from this study suggest that FCH is preferable to FDG for PET of prostate carcinoma and support the need for future validation studies in a larger number of subjects.

We investigated the potential of carbon-11 choline positron emission tomography (PET) for the detection of lymph node and bone metastases in prostate cancer. A total of 23 patients were studied (known metastases: 8; suspicion of metastases: 3; primary staging: 12). Whole-body PET imaging was performed 5 min after injection of the tracer and completed within 1 h. Focally increased tracer uptake in bone or abdominal lymph node regions was interpreted as representing tumour involvement. All known bone and lymph node metastases could be recognized by [11C]choline PET. One out of ten negative scans for primary staging was false-negative (lymph node <1 cm) and one out of two positive scans was false-positive with regard to lymph node involvement (focal bowel activity). It is concluded that [11C]choline PET is a promising new tool for the primary staging of prostate cancer, with lymph node and bone metastases demonstrating high tracer uptake. Therapeutic management could be influenced by these results in that the technique may permit avoidance of surgical lymph node exploration.