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Positron-emission tomography (PET) is an important oncologic imaging tool for primary tumor staging, evaluation of treatment response, recurrence detection, and restaging. Combined with computed tomography (CT), PET/CT has increased the diagnostic accuracy and dramatically reduced the acquisition time. This article describes the normal uptake, distribution, and excretion of Fluorine-18-labeled deoxyglucose (18F FDG) as well as normal variations, response to treatment regimes, artifacts, and potential pitfalls that are important for correct image interpretation of whole-body PET/CT in oncology. [ABSTRACT FROM AUTHOR]

Background: The main objective is to discuss why treatment of non-prostate cancers with [ 177 Lu]Lu-PSMA-radioligand achieved only low tumor dose in most published cases, despite high uptake on PSMA PET. We use a patient with renal cell carcinoma as an illustrative example. Furthermore, we discuss how the problem with early washout and low tumor dose might be overcome by using a radionuclide with shorter half-life, matching the target binding residence time., Case Presentation: [ 68 Ga]Ga-PSMA-11 PET/CT of a 56-year old man with metastatic renal cell carcinoma showed high lesion uptake. One dose of 6.9 GBq [ 177 Lu]Lu-PSMA-I&T was administrated. Post-therapy dosimetry was performed with SPECT/CT and whole-body planar imaging after 5, 24 and 48 h. Doses to target lesions were only 0.2-0.5 Gy. No treatment effect was achieved., Conclusion: Rapid tumor washout of [ 177 Lu]Lu-PSMA-I&T and low tumor dose despite high uptake of [ 68 Ga]Ga-PSMA-11 are most likely caused by localization of PSMA-receptors on neovasculature rather than on the tumor cells, and unlike in prostate cancer cells, the PSMA-RL / PSMA-receptor complex is not internalized. To overcome the problem with early washout, the use of a radionuclide with shorter half-life matching the target binding residence time will be needed., (© 2024. The Author(s).)

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.)

Background: Treatment of castration-resistant metastatic prostate cancer with [¹⁷⁷Lu]PSMA radioligand., Case Presentation: A man in his seventies with metastatic prostate cancer received castration therapy for four years, developing castration-resistant disease. PET/CT with [⁶⁸Ga]PSMA-11 showed high uptake in metastatic lymph nodes. The patient received 7.4 GBq [¹⁷⁷Lu]PSMA-I&T (Curium, Finland) as five treatments at five-week intervals. Five weeks after the first treatment, p-PSA dropped from 154 to 53 µg/L. Five weeks after the fifth treatment, p-PSA was 1.8 µg/L. [⁶⁸Ga]PSMA-11 PET/CT showed significant reduction in the size of metastases, with the largest decreasing in diameter from 10 to 4 mm. Seven months after the fifth treatment, p-PSA increased to 14.3 µg/L, and [⁶⁸Ga]PSMA-11 PET/ CT revealed additional skeletal metastases, while the lymph node metastases remained unchanged. Thus, the treatment had a good but temporary effect on the metastases., Interpretation: Treatment with [¹⁷⁷Lu]PSMA radioligand resulted in a temporary regression of the metastases.

Background: Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) can change management in a large fraction of patients with biochemically recurrent prostate cancer (BCR)., Purpose: To investigate the added value of PET to MRI and CT for this patient group, and to explore whether the choice of the PET paired modality (PET/MRI vs. PET/CT) impacts detection rates and clinical management., Study Type: Retrospective., Subjects: 41 patients with BCR (median age [range]: 68 [55-78])., Field Strength/sequence: 3T, including T1-weighted gradient echo (GRE), T2-weighted turbo spin echo (TSE) and dynamic contrast-enhanced GRE sequences, diffusion-weighted echo-planar imaging, and a T1-weighted TSE spine sequence. In addition to MRI, [ 18 F]PSMA-1007 PET and low-dose CT were acquired on the same day., Assessment: Images were reported using a five-point Likert scale by two teams each consisting of a radiologist and a nuclear medicine physician. The radiologist performed a reading using CT and MRI data and a joint reading between radiologist and nuclear medicine physician was performed using MRI, CT, and PET from either PET/MRI or PET/CT. Findings were presented to an oncologist to create intended treatment plans. Intrareader and interreader agreement analysis was performed., Statistical Tests: McNemar test, Cohen's κ, and intraclass correlation coefficients. A P-value <0.05 was considered significant., Results: 7 patients had positive findings on MRI and CT, 22 patients on joint reading with PET/CT, and 18 patients joint reading with PET/MRI. For overall positivity, interreader agreement was poor for MR and CT (κ = 0.36) and almost perfect with addition of PET (PET/CT κ = 0.85, PET/MRI κ = 0.85). The addition of PET from PET/CT and PET/MRI changed intended treatment in 20 and 18 patients, respectively. Between joint readings, intended treatment was different for eight patients., Data Conclusion: The addition of [ 18 F]PSMA-1007 PET/MRI or PET/CT to MRI and CT may increase detection rates, could reduce interreader variability, and may change intended treatment in half of patients with BCR., Level of Evidence: 3 TECHNICAL EFFICACY: Stage 3., (© 2024 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Purpose: The primary aim was to evaluate whether anti-3-[ 18 F]FACBC PET combined with conventional MRI correlated better with histomolecular diagnosis (reference standard) than MRI alone in glioma diagnostics. The ability of anti-3-[ 18 F]FACBC to differentiate between molecular and histopathological entities in gliomas was also evaluated., Methods: In this prospective study, patients with suspected primary or recurrent gliomas were recruited from two sites in Norway and examined with PET/MRI prior to surgery. Anti-3-[ 18 F]FACBC uptake (TBR peak ) was compared to histomolecular features in 36 patients. PET results were then added to clinical MRI readings (performed by two neuroradiologists, blinded for histomolecular results and PET data) to assess the predicted tumor characteristics with and without PET., Results: Histomolecular analyses revealed two CNS WHO grade 1, nine grade 2, eight grade 3, and 17 grade 4 gliomas. All tumors were visible on MRI FLAIR. The sensitivity of contrast-enhanced MRI and anti-3-[ 18 F]FACBC PET was 61% (95%CI [45, 77]) and 72% (95%CI [58, 87]), respectively, in the detection of gliomas. Median TBR peak was 7.1 (range: 1.4-19.2) for PET positive tumors. All CNS WHO grade 1 pilocytic astrocytomas/gangliogliomas, grade 3 oligodendrogliomas, and grade 4 glioblastomas/astrocytomas were PET positive, while 25% of grade 2-3 astrocytomas and 56% of grade 2-3 oligodendrogliomas were PET positive. Generally, TBR peak increased with malignancy grade for diffuse gliomas. A significant difference in PET uptake between CNS WHO grade 2 and 4 gliomas (p < 0.001) and between grade 3 and 4 gliomas (p = 0.002) was observed. Diffuse IDH wildtype gliomas had significantly higher TBR peak compared to IDH1/2 mutated gliomas (p < 0.001). Adding anti-3-[ 18 F]FACBC PET to MRI improved the accuracy of predicted glioma grades, types, and IDH status, and yielded 13.9 and 16.7 percentage point improvement in the overall diagnoses for both readers, respectively., Conclusion: Anti-3-[ 18 F]FACBC PET demonstrated high uptake in the majority of gliomas, especially in IDH wildtype gliomas, and improved the accuracy of preoperatively predicted glioma diagnoses., Clinical Trial Registration: ClinicalTrials.gov ID: NCT04111588, URL: https://clinicaltrials.gov/study/NCT04111588., (© 2023. The Author(s).)

Purpose: Glioblastoma multiforme (GBM) is the most common glioma and standard therapies can only slightly prolong the survival. Neo-vascularization is a potential target to image tumor microenvironment, as it defines its brain invasion. We investigate [ 18 F]rhPSMA-7.3 with PET/MRI for quantitative imaging of neo-vascularization in GBM bearing mice and human tumor tissue and compare it to [ 18 F]FET and [ 18 F]fluciclovine using PET pharmacokinetic modeling (PKM)., Methods: [ 18 F]rhPSMA-7.3, [ 18 F]FET, and [ 18 F]fluciclovine were i.v. injected with 10.5 ± 3.1 MBq, 8.0 ± 2.2 MBq, 11.5 ± 1.9 MBq (n = 28, GL261-luc2) and up to 90 min PET/MR imaged 21/28 days after surgery. Regions of interest were delineated on T2-weighted MRI for (i) tumor, (ii) brain, and (iii) the inferior vena cava. Time-activity curves were expressed as SUV mean, SUVR and PKM performed using 1-/2-tissue-compartment models (1TCM, 2TCM), Patlak and Logan analysis (LA). Immunofluorescent staining (IFS), western blotting, and autoradiography of tumor tissue were performed for result validation., Results: [ 18 F]rhPSMA-7.3 showed a tumor uptake with a tumor-to-background-ratio (TBR) = 2.1-2.5, in 15-60 min. PKM (2TCM) confirmed higher K1 (0.34/0.08, p = 0.0012) and volume of distribution V T (0.24/0.1, p = 0.0017) in the tumor region compared to the brain. Linearity in LA and similar k3 = 0.6 and k4 = 0.47 (2TCM, tumor, p = ns) indicated reversible binding. K1, an indicator for vascularization, increased (0.1/0.34, 21 to 28 days, p < 0.005). IFS confirmed co-expression of PSMA and tumor vascularization. [ 18 F]fluciclovine showed higher TBR (2.5/1.8, p < 0.001, 60 min) and V S (1.3/0.7, p < 0.05, tumor) compared to [ 18 F]FET and LA indicated reversible binding. V T increased (p < 0.001, tumor, 21 to 28 days) for [ 18 F]FET (0.5-1.4) and [ 18 F]fluciclovine (0.84-1.5)., Conclusion: [ 18 F]rhPSMA-7.3 showed to be a potential candidate to investigate the tumor microenvironment of GBM. Following PKM, this uptake was associated with tumor vascularization. In contrast to what is known from PSMA-PET in prostate cancer, reversible binding was found for [ 18 F]rhPSMA-7.3 in GBM, contradicting cellular trapping. Finally, [ 18 F]fluciclovine was superior to [ 18 F]FET rendering it more suitable for PET imaging of GBM., (© 2022. The Author(s).)

Purpose: The study aims to evaluate whether combined 18 F-FACBC PET/MRI could provide additional diagnostic information compared with MRI alone in brain metastases., Patients and Methods: Eighteen patients with newly diagnosed or suspected recurrence of brain metastases received dynamic 18 F-FACBC PET/MRI. Lesion detection was evaluated on PET and MRI scans in 2 groups depending on prior stereotactic radiosurgery (SRS group) or not (no-SRS group). SUVs, time-activity curves, and volumetric analyses of the lesions were performed., Results: In the no-SRS group, 29/29 brain lesions were defined as "MRI positive." With PET, 19/29 lesions were detected and had high tumor-to-background ratios (TBRs) (D max MR , ≥7 mm; SUV max , 1.2-8.4; TBR, 3.9-25.9), whereas 10/29 lesions were undetected (D max MR , ≤8 mm; SUV max , 0.3-1.2; TBR, 1.0-2.7). In the SRS group, 4/6 lesions were defined as "MRI positive," whereas 2/6 lesions were defined as "MRI negative" indicative of radiation necrosis. All 6 lesions were detected with PET (D max MR , ≥15 mm; SUV max , 1.4-4.2; TBR, 3.6-12.6). PET volumes correlated and were comparable in size with contrast-enhanced MRI volumes but were only partially congruent (mean DSC, 0.66). All time-activity curves had an early peak, followed by a plateau or a decreasing slope., Conclusions: 18 F-FACBC PET demonstrated uptake in brain metastases from cancer of different origins (lung, gastrointestinal tract, breast, thyroid, and malignant melanoma). However, 18 F-FACBC PET/MRI did not improve detection of brain metastases compared with MRI but might detect tumor tissue beyond contrast enhancement on MRI. 18 F-FACBC PET should be further evaluated in recurrent brain metastases., Competing Interests: Conflicts of interest and sources of funding: The authors declare that they have no conflicts of interest. The work was supported by Trond Mohn Foundation., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: The aim of this prospective study was to investigate the prognostic value of metabolic tumor volume (MTV) and apparent diffusion coefficient (ADC) from baseline FDG PET/MRI compared to established clinical risk factors in terms of progression free survival (PFS) at 2 years in a cohort of diffuse large B-cell Lymphoma (DLBCL) and high-grade-B-cell lymphoma (HGBCL)., Methods: Thirty-three patients and their baseline PET/MRI examinations were included. Images were read by two pairs of nuclear medicine physicians and radiologists for defining lymphoma lesions. MTV was computed on PET, and up to six lymphoma target lesions with restricted diffusion was defined for each PET/MRI examination. Minimum ADC (ADC min ) and the corresponding mean ADC (ADC mean ) from the target lesion with the lowest ADC min were included in the analyses. For the combined PET/MRI parameters, the ratio between MTV and the target lesion with the lowest ADC min (MTV/ADC min) and the corresponding ADC mean (MTV/ADC mean ) was calculated for each patient. Clinical, histological, and PET/MRI parameters were compared between the treatment failure and treatment response group, while survival analyses for each variable was performed by using univariate Cox regression. In case of significant variables in the Cox regression analyses, Kaplan-Meier survival analyses with log-rank test was used to study the effect of the variables on PFS., Results: ECOC PS scale ≥2 (p = 0.05) and ADC mean (p = 0.05) were significantly different between the treatment failure group (n = 6) and those with treatment response (n = 27). Survival analyses showed that ADC mean was associated with PFS (p = 0.02, [HR 2.3 for 1 SD increase]), while combining MTV and ADC did not predict outcome. In addition, ECOG PS ≥2 (p = 0.01, [HR 13.3]) and histology of HGBCL (p = 0.02 [HR 7.6]) was significantly associated with PFS., Conclusions: ADC mean derived from baseline MRI could be a prognostic imaging biomarker for DLBCL and HGBCL. Baseline staging with PET/MRI could therefore give supplementary prognostic information compared to today's standard PET/CT., (© 2022. The Author(s).)

Background: 18F-fluciclovine is a positron emission tomography (PET) radiotracer approved for the detection of prostate cancer recurrence. No effect of androgen deprivation therapy (ADT) on its performance has been established. Purpose: To study the impact of concurrent ADT on disease detection with 18F-fluciclovine PET in patients with prostate cancer. Materials and Methods: Data from patients with prostate cancer who had been receiving ADT for ≥3 months at the time of undergoing an 18F-fluciclovine PET/CT at our institution were retrospectively reviewed. Seventy-three scans from 71 patients were included. The scans indicated rising prostate-specific antigen (n = 58), staging advanced disease (n = 4) or therapeutic monitoring (n = 9). Patients’ medical records provided baseline clinical data and post-scan outcomes (median follow-up 40 months). Results: Malignant lesions with increased uptake of 18F-fluciclovine were detected in 60/73 (82%) scans; 33 (45%) had lesions in the prostate/bed and 46 (63%) in extraprostatic sites. Patients received ADT for a median of 2 years (range 3 months to >10 years) pre-scan. The time on ADT did not influence detection; the detection rates were 89% for patients who had received ADT for <1 year, 63% for a treatment period of 1−<2 years, 83% for 2−4 years, 78% for >4−10 years, and 67% for a treatment period of >10 years. Conclusion: 18F-fluciclovine detected recurrent or metastatic lesions in 82% of patients with prostate cancer receiving ADT. The rates achieved in the present study are consistent with widely reported data for 18F-fluciclovine PET/CT, suggesting that withdrawal of ADT before scanning is not necessary.

Abstract: A previously published model (Atkins) allows for calculation of 131I maximum tolerated activity on the basis of 48-hour whole-body retention of 131I on a pretherapy diagnostic scan. Our practice uses iodine 123I for diagnostic imaging of metastatic thyroid cancer for staging before 131I therapy, with images typically acquired 24 hours after administration of the radiopharmaceutical. We explored the feasibility of an additional 123I whole-body scan and retention measurement at 48 hours, with application of the model to estimate maximum tolerated activity of radioiodine before 131I treatment of metastatic thyroid cancer., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

The aim of this guideline is to provide standards for the recommendation, performance, interpretation, and reporting of [ 18 F]Fluciclovine PET/CT for prostate cancer imaging. These recommendations will help to improve accuracy, precision, and repeatability of [ 18 F]Fluciclovine PET/CT for prostate cancer essentially needed for implementation of this modality in science and routine clinical practice.

Background and Purpose: Standardized uptake value (SUV) and related parameters derived from 2-deoxy-2-[18F]-fluoro-d-glucose (FDG) PET/CT prior to radiochemotherapy of head and neck cancer (HNC) were significantly associated with survival in a number of studies. The aim of this study was to validate these findings and to evaluate the prognostic role of PET parameters also including clinical factors and HPV status., Materials and Methods: We reviewed 166 HNC cases with a radiotherapy planning FDG PET/CT scan. All patients received radiotherapy, 68-70 Gy with or without concomitant cisplatin. Primary endpoint was disease-free survival (DFS). Twelve clinical factors, including HPV, performance status, stage and treatment parameters and ten PET/CT image parameters including gross tumor volume (GTV), metastatic lymph node volume, SUVmax, metabolic tumor volume (MTV) and total lesion glycolysis (TLG), were collected. Univariate and multivariate Cox regression analyses were employed., Results: Of the 166 patients included, 48 had locoregional and 23 had metastatic recurrence. None of the FDG PET parameters were significant in the univariate analysis using DFS as endpoint. HPV status, ECOG status and GTV-U (primary tumor and lymph node volume from CT) were statistically significant (p < 0.01). Only in the subgroup of HPV-unrelated HNC (HPV negative oropharyngeal cancer [OPC] and non-OPC; n = 73), the multivariate model could be improved by including MTV (p < 0.001). DFS events were 29 (31%) in HPV-related and 53 (73%) in HPV-unrelated HNC., Conclusion: FDG PET parameters appear less important for overall prognostication of radiochemotherapy outcome for HNC. Still, the association between the FDG PET parameters and survival is strong for HNC not related to HPV. Tumor volume from CT is generally more closely related to outcome than parameters derived from FDG PET/CT., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose: To retrospectively investigate the uptake of F-fluciclovine on PET/CT in patients with suspected recurrent high-grade glioma (HGG)., Methods: Twenty-one patients were included. The standard of truth was histopathologic interpretation if available. When histopathology was not available or rebiopsy did not show signs of malignancy, clinical follow-up including MRI and clinical outcome was considered the standard of truth., Results: All 21 patients met the reference standard of either histopathologic proof of HGG recurrence (n = 10) or disease progression clinically and with tumor growth corresponding to the primary tumor sites on follow-up MRI (n = 11). Median time from PET/CT to death was 5 months (range, 1-20 months). Median time from primary diagnosis to death was 14.5 months (range, 6 to >400). Average SUVmax of the lesions was 8.3 ± 5.3 (SD) and 0.34 ± 0.13 for normal brain tissue. Median lesion-to-background ratio was 21.6 (range, 3.1-84.4). In 4 patients, F-fluciclovine PET/CT detected small satellite tumors that had not been reported on MR., Conclusions: The uptake of F-fluciclovine in clinically and/or histopathologically confirmed recurrent HGG is high compared with the uptake reported for other amino acid PET tracers. Because of the high tumor uptake and thus high tracer contrast, small satellite tumors with a diameter below usual reported PET spatial resolution and not reported on MRI were detected in 4 patients. As no patients with confirmed treatment-related changes were included, we cannot as of yet ascertain the ability of F-fluciclovine PET to discriminate between recurrent HGG and treatment-related changes, for example, pseudoprogression and radionecrosis.

Background: Semi-automated quantitative measurement of metabolic tumor volume (MTV) for prognosis in diffuse large B-Cell lymphoma (DLBCL) has gained considerable interest lately. However, simple tumor volume measures may be inadequate for assessment of prognosis in DLBCL as other characteristics such as growth pattern and metabolic heterogeneity may be just as important. In addition, MTV measurements require delineation of tumor lesions by semi-automated software, which can be time-consuming. We hypothesized that a simple visual assessment of tumor volume performs as well as standardized MTV measurements in DLBCL prognostication., Materials and Methods: Quantitative and visual analyses of pre-therapy 18F-FDG PET/CT scans in 118 patients with newly diagnosed DLBCL were conducted. Quantitative analyses were performed using Hermes TumourFinder® to obtain MTV 2.5 (SUV 2.5 cut-off) and MTV 41 (41% SUVmax isocontour cut-off). Visual assessments included a binary prediction (good/poor prognosis) as well as tumor burden based on a visual analog scale (MTV VAS ) and an estimated volume (eMTV). Three experienced nuclear medicine physicians who were blinded to clinical outcome performed visual evaluations. Progression-free survival was evaluated by Kaplan-Meier curves and log-rank test. Inter-observer variability was evaluated by Fleiss' kappa for multiple observers., Results: In the quantitative analysis, a ROC-determined MTV 2.5 cut-off (log-rank p = 0.11) seemed to outperform MTV 41 (log-rank p = 0.76) for PFS prediction. TLG2.5 (log-rank p = 0.14) and TLG41 (log-rank p = 0.34) were not associated with outcomes. By visual analysis, all three reviewers were able to stratify patients into good/poor prognosis (reviewer A log-rank p = 0.002, reviewer B log-rank p = 0.016, and reviewer C log-rank p = 0.012) with fair inter-observer agreement (Fleiss' kappa 0.47). MTV VAS and eMTV were not consistently correlated with the outcome., Conclusion: Predictions of outcome after first-line treatment for DLBCL were surprisingly good when left to the unsupervised, subjective judgment of experienced readers of lymphoma 18F-FDG-PET/CT. The study highlights the importance of non-standardized clinical judgments and shows potential loss of valuable prognostic information when relying solely on semi-automated MTV measurements.

Purpose: To estimate the diagnostic accuracy of conventional 18F-FDG PET/CT of cranial arteries in the diagnosis of giant cell arteritis (GCA)., Methods: The study was a retrospective case-control study. The reference diagnosis was fulfillment of the 1990 ACR criteria for GCA. All patients had new-onset GCA. Conventional 18F-FDG PET/CT was performed before glucocorticoid treatment. Controls were age- and sex-matched patients with a previous history of malignant melanoma (MM) undergoing surveillance PET/CT >6 months after MM resection. PET images were evenly cropped to include only head and neck and were assessed in random order by four nuclear medicine physicians blinded to reference diagnosis. Temporal (TA), maxillary (MA) and vertebral (VA) arteries were visually rated for 18F-FDG uptake. Interreader agreement was evaluated by Fleiss kappa., Results: A total of 44 patients and 44 controls were identified. In both groups, the mean age was 69 years (p = 0.45) and 25/44 were women. 35/41 GCA patients were temporal artery biopsy positive (TAB). Considering only FDG uptake in TA and/or MA, diagnostic sensitivity and specificity was 64 and 100%. Including VA, sensitivity increased to 82% and specificity remained 100%. Interreader agreement was 91% and Fleiss kappa 0.82 for the PET diagnosis based on the cranial arteries., Conclusion: Conventional 18F-FDG PET/CT is an accurate and reliable tool to diagnose cranial arteritis in glucocorticoid-naïve GCA patients. The high diagnostic specificity suggests that TAB can be omitted in patients with 18F-FDG uptake in cranial arteries. 18F-FDG PET/CT performed in patients with suspected vasculitis should always include the head and neck.

Background: For patients with recurrent or second primary disease, re-irradiation can be challenging due to overlap with previously irradiated volumes. Dose painting may be attractive for these patients, as the focus is on delivering maximal dose to areas of high tumor activity. Here, we compare dose painting by contours (DPBC) treatment plans based on 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) with conventional plans., Material and Methods: We included 10 patients with recurrent or second primary head and neck cancer (HNC) eligible for re-irradiation. Our conventional re-irradiation regimen is hyperfractionated radiotherapy 1.5 Gy twice daily over 4 weeks, giving a total dose of 60 Gy. For DPBC, we defined two prescription volumes, PV33 and PV66, corresponding to 33 and 66% of the highest FDG uptake in the tumor. The clinical target volume (CTV) prescription dose was 60 Gy, PV33; 65-67 Gy and PV66; 70-73 Gy. The DPBC plan is to be given the first 20 fractions and the conventional plan the last 20 fractions. Dose to organs at risk (OARs) were compared for DPBC and conventional treatment. By summation of the initial curative plan and the re-irradiation plan, we also evaluated differences in dose to the 2 ccm hot spot (D 2cc )., Results: We achieved DPBC plans with adequate target coverage for all 10 patients. There were no significant differences in OAR doses between the standard plans and the DPBC plans (p=.7). Summation of the initial curative plan and the re-irradiation plan showed that the median D 2cc increased from 130 Gy (range 113-132 Gy; conventional) to 140 Gy (range 115-145 Gy; DPBC)., Conclusions: Our proposed DPBC could be straightforwardly implemented and all plans met the objectives. Re-irradiation of HNC with DPBC may increase tumor control without more side effects compared to conventional radiotherapy.

Purpose: Radiation therapy effectively kills cancer cells and elicits local effects in the irradiated tissue. The aim of this study was to investigate the kinetics of cytokines in the serum of patients with lung cancer undergoing radiation therapy and to identify associations with metabolic tumor burden as determined by 2-deoxy-2-fluoro-D-glucose ( 18 F-FDG) positron emission tomography (PET)., Methods and Materials: Forty-five patients with advanced non-small cell lung cancer were included in a phase 2 clinical trial and randomized between fractionated thoracic radiation therapy alone or concurrent with an epidermal growth factor receptor inhibitor. Blood was sampled at 4 different time points: prior to treatment, midtherapy, at the end of therapy, and 6 to 8 weeks after the start of treatment. The serum concentrations of 48 cytokines and 9 matrix metalloproteinases were measured with multiplex immunoassays. A subset of patients was examined by 18 F-FDG PET/computed tomography before, during, and after radiation therapy. The maximum standardized uptake values (SUV max ) of the primary lung tumor, whole-body metabolic tumor volume, and total lesion glycolysis were calculated, and correlations between the PET parameters and cytokines were investigated., Results: The SUV max decreased from baseline through midtherapy to posttherapy 18 F-FDG PET/computed tomography ( P  = .018). The serum levels of C-C motif chemokine ligand (CCL) 23, CCL24, C-X3-C motif chemokine ligand 1, and interleukin-8 (C-X-C motif ligand [CXCL]8) were significantly correlated to SUV max , metabolic tumor volume, and total lesion glycolysis before, during, and after radiation therapy. CXCL2 ( P  = .030) and CXCL6 ( P  = .010) decreased after the start of therapy and changed significantly across the sample time points. Serum concentrations of CCL15 ( P  = .031), CXCL2 ( P  = .028), and interleukin-6 ( P  = .007) were positively correlated to the irradiated volume during the second week of treatment., Conclusions: Cytokine serum levels vary and correlate with metabolic tumor burden in patients with advanced non-small cell lung cancer undergoing palliative thoracic radiation therapy.

Background: Glucose metabolism can be studied in vitro by a variety of means, also by fluorodeoxyglucose (FDG). As an example of the potential use we have compared the high glucose consumption in cancer cells and in transformed non-malignant foetal cells. The high glucose metabolism in cancer cells is not primarily for the production of energy, a large proportion is transformed to lactate only, producing two instead of potentially 32 ATP equivalents. The secreted lactate reduces the pH in the local microenvironment and gives malignant cells, more apt to thrive in hypoxic and acid environments, a competitive advantage., Purpose: To demonstrate the use of FDG in head-to-head comparison of glucose uptake and lactate production in a highly malignant and a highly proliferative non-malignant cell line., Materials and Methods: Cell cultures of a foetal kidney cell line and a triple negative breast cancer cell line were incubated with FDG for one hour, washed, harvested and the radioactivity content in the cells was measured in a well counter. The lactate concentration was measured in conditioned medium., Results: The FDG uptake was consistently higher in the non-malignant foetal cell line. The levels of lactate in the conditioned medium were similar., Conclusion: Quantitative comparison of glucose metabolism by in vitro use of FDG is a practical, cheap and rapid method. Some foetal cells have higher glucose uptake and produce as much lactate as this highly malignant cell line. This is an argument against the high glucose consumption being related solely to malignancy., (© 2016 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.)

Background: PET image reconstruction methods include modeling of resolution degrading phenomena, often referred to as point-spread function (PSF) reconstruction. The aim of this study was to develop a clinically relevant phantom and characterize the reproducibility and accuracy of high-resolution PSF reconstructed images of small lesions, which is a prerequisite for using PET in the prediction and evaluation of responses to treatment. Sets of small homogeneous 18 F-spheres (range 3-12 mm diameter, relevant for small lesions and lymph nodes) were suspended and covered by a 11 C-silicone, which provided a scattering medium and a varying sphere-to-background ratio. Repeated measurements were made on PET/CT scanners from two vendors using a wide range of reconstruction parameters. Recovery coefficients (RCs) were measured for clinically used volume-of-interest definitions., Results: For non-PSF images, RCs were reproducible and fell monotonically as the sphere diameter decreased, which is the expected behavior. PSF images converged slower and had artifacts: RCs did not fall monotonically as sphere diameters decreased but had a maximum RC for sphere sizes around 8 mm, RCs could be greater than 1, and RCs were less reproducible. To some degree, post-reconstruction filters could suppress PSF artifacts., Conclusions: High-resolution PSF images of small lesions showed artifacts that could lead to serious misinterpretations when used for monitoring treatment response. Thus, it could be safer to use non-PSF reconstruction for quantitative purposes unless PSF reconstruction parameters are optimized for the specific task.

Purpose: Sensitive detection of cancer foci in men experiencing biochemical recurrence following initial treatment of prostate cancer is of great clinical significance with a possible impact on subsequent treatment choice. We describe a multisite experience of the efficacy and safety of the positron emission tomography/computerized tomography agent fluciclovine ( 18 F) after biochemical recurrence., Materials and Methods: A total of 596 patients underwent fluciclovine ( 18 F) positron emission tomography/computerized tomography at 4 clinical sites. Detection rate determinations were stratified by the baseline prostate specific antigen value. Diagnostic performance was assessed against a histological reference standard in 143 scans., Results: The subject level fluciclovine ( 18 F) positron emission tomography/computer tomography detection rate was 67.7% (403 of 595 scans). Positive findings were detected in the prostate/bed and pelvic lymph node regions in 38.7% (232 of 599) and 32.6% of scans (194 of 596), respectively. Metastatic involvement outside the pelvis was detected in 26.2% of scans (155 of 591). The subject level detection rate in patients in the lowest quartile for baseline prostate specific antigen (0.79 ng/ml or less) was 41.4% (53 of 128). Of these patients 13 had involvement in the prostate/bed only, 16 had pelvic lymph node involvement without distant disease and 24 had distant metastases. The positive predictive value of fluciclovine ( 18 F) positron emission tomography/computerized tomography scanning for all sampled lesions was 62.2%, and it was 92.3% and 71.8% for extraprostatic and prostate/bed involvement, respectively. Fluciclovine ( 18 F) was well tolerated and the safety profile was not altered following repeat administration., Conclusions: Fluciclovine ( 18 F) is well tolerated and able to detect local and distant prostate cancer recurrence across a wide range of prostate specific antigen values., (Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

FDG PET/CT is perceived as a valuable diagnostic tool in addition to the standard diagnostic workup for patients with isolated neck lymph nodes of squamous cell carcinoma of unknown primary (SCCUP). For patients with SCCUP intended for primary radiotherapy, we hypothesize that the previously reported FDG PET/CT detection rates are too high. From 2008 to 2015, 30 SCCUP patients were examined with FDG PET/CT. The objective of the FDG PET/CT examination was twofold: (1) improve the radiotherapy target definition, and (2) identify the primary cancer. Before the FDG PET/CT, the patients had been through a standard workup consisting of CT of the neck and chest, examination with flexible endoscopy with patient awake, panendoscopy and examination under general anesthesia, tonsillectomy and sometimes blind sampling biopsies, and MRI (floor of the mouth). All FDG PET/CTs were performed applying a flat table, head support and fixation mask as part of the radiotherapy treatment planning. Diagnostic CT with contrast was an integrated part of the PET/CT examination. Only 1/30 patients (cancer of the vallecula) had their primary cancer detected by FDG PET/CT. In addition, a non-biopsied patient with high uptake in the ipsilateral palatine tonsil was included, giving a detection rate of ≤7 % (95 % CI 2-21 %). In this retrospective study, we found that the FDG PET/CT detection rate of the primary for SCCUP patients is lower than previously reported. It is questionable whether FDG PET/CT is necessary for these patients when improved, advanced workup is available.

Background: Positron emission tomography (PET) with the liver-specific galactose tracer 2-[(18)F]fluoro-2-deoxy-D-galactose ((18)F-FDGal) may improve diagnosis of hepatocellular carcinoma (HCC). The aim of this study was to test which of three different (18)F-FDGal PET protocols gives the highest tumour-to-background (T/B) ratio on PET images and thus better detection of HCC tumours., Methods: Ten patients with a total of 15 hepatic HCC tumours were enrolled prior to treatment. An experienced radiologist defined volumes of interest (VOIs) encircling HCC tumours on contrast-enhanced CT (ce-CT) images. Three PET/CT protocols were conducted following an intravenous (18)F-FDGal injection: (i) a 20-min dynamic PET/CT of the liver (to generate a 3D metabolic image), (ii) a traditional static whole-body PET/CT after 1 h, and (iii) a late static whole-body PET/CT after 2 or 3 h. PET images from each PET/CT protocol were fused with ce-CT images, and the average standardized uptake values (SUV) in tumour and background liver tissue were used to calculate (T/B) ratios. Furthermore, Tpeak/B ratios were calculated using the five hottest voxels in all hot tumours. The ratios for the three different PET protocols were compared., Results: For the individual tumours, there was no significant difference in the T/B ratio between the three PET protocols. The metabolic image yielded higher Tpeak/B ratios than the two static images, but it was easier to identify tumours on the static images. One extrahepatic metastasis was detected., Conclusions: Neither metabolic images nor static whole-body images acquired 2 or 3 h after (18)F-FDGal injection offered an advantage to traditional whole-body PET/CT images acquired after 1 h for detection of HCC.

Purpose: To evaluate the diagnostic performance of a new method for respiratory gated positron emission tomography (rgPET/CT) for colorectal liver metastases (CRLM), secondly, to assess its additional value to standard PET/CT (PET/CT)., Materials and Methods: Forty-three patients scheduled for resection of suspected CRLM were prospectively included from September 2011 to January 2013. None of the patients had previously undergone treatment for their CRLM. All patients underwent PET/CT and rgPET/CT in the same session. For rgPET/CT an in-house developed electronic circuit was used which displayed a color-coded countdown for the patient. The patients held their breath according to the countdown and only the data from the inspiration breath-hold period was used for image reconstruction. Two independent and blinded readers evaluated both PET/CT and rgPET/CT separately. The reference standard was histopathological confirmation for 73 out of 131 CRLM and follow-up otherwise., Results: Reference standard identified 131 CRLM in 39/43 patients. Nine patients accounted for 25 mucinous CRLM. The overall per-lesion sensitivity for detection of CRLM was for PET/CT 60.0%, for rgPET/CT 63.1%, and for standard+rgPET/CT 67.7%, respectively. Standard+rgPET/CT was overall significantly more sensitive for CRLM compared to PET/CT (p=0.002) and rgPET/CT (p=0.031). The overall positive predictive value (PPV) for detection of CRLM was for PET/CT 97.5%, for rgPET/CT 95.3%, and for standard+rgPET/CT 93.6%, respectively., Conclusion: Combination of PET/CT and rgPET/CT improved the sensitivity significantly for CRLM. However, high patient compliance is mandatory to achieve optimal performance and further improvements are needed to overcome these limitations. The diagnostic performance of the evaluated new method for rgPET/CT was comparable to earlier reported technically more complex and expensive methods., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: The aim of this study was to assess treatment-related changes in prostate-specific antigen (PSA), total and bone alkaline phosphatase (total ALP, bone ALP), and changes on conventional bone scans in patients with metastatic castration-resistant prostate cancer (mCRPC) with bone metastases who received six cycles of radium-223 (Ra-223)., Materials and Methods: Changes in PSA, total ALP and bone ALP (≥30% increase or decrease), and changes on bone scans were assessed before and after six monthly cycles of Ra-223 therapy (50 kBq/kg body weight) in 14 patients with mCRPC with bone metastases and four patients on placebo., Results: Post-treatment PSA increased by at least 30% in 11 out of 14 patients and remained stable in three. Total ALP and bone ALP decreased in six and nine patients, respectively. In 10 out of 12 evaluable patients the uptake on post-treatment bone scan was reduced in lesions with high pretreatment uptake, in 11 patients accompanied by the development of new or expanded bone lesions. FACBC position emission tomography/computed tomography scans confirmed the growth of new or expanded bone metastases in two patients., Conclusions: These observations support the notion that Ra-223 kills tumour cells in metastases surrounded by highly proliferating osteoblasts, consistent with the reported survival benefit. The radiation effect in small tumour deposits not surrounded by increased osteoblast activity seems, however, insufficient, thus allowing continuous tumour growth. Long-lasting PSA reductions are the exception rather than the rule during Ra-223 treatment, whereas alkaline phosphatases decrease more frequently. To improve the overall anticancer effect, Ra-223 might be a valuable component of combination treatment.

Background: 18F fluoro-deoxyglucose (FDG) positron emission tomography / computed tomography (PET/CT) is a well-recognized diagnostic tool used for staging and monitoring of therapy response for lymphomas. During the past decade diffusion-weighted (DW) magnetic resonance imaging (MRI) is increasingly being included in the assessment of tumor response for various cancers., Purpose: To compare the change in maximum standardized uptake value (ΔSUVmax) from FDG PET/CT with the change in apparent diffusion coefficient (ΔADC) from DW MRI after initiation of the first cycle of chemotherapy in patients with Hodgkin's lymphoma (HL) and in patients with diffuse large B-cell lymphoma (DLBCL)., Material and Methods: Twenty-seven consecutive patients with histologically proven lymphoma and lymphomatous lymph nodes (LLN) of the neck (19 with HL, 8 with DLBCL) underwent FDG PET/CT and MRI of the neck before and after initiation of the first cycle of chemotherapy. The mean time interval from initiation of chemotherapy to imaging was 19 days and 2 days for FDG PET/CT and MRI, respectively. For each patient ΔSUVmax, ΔADC, and change in volume of the same LLN were compared., Results: There was a significant mean decrease of SUVmax by 70%, but no significant change in ADC. There was no significant reduction in LLN volume., Conclusion: There was no significant correlation between ΔSUVmax and ΔADC. Thus, our data do not support that FDG PET/CT can be replaced by early DW MRI for response evaluation in lymphoma patients., (© The Foundation Acta Radiologica 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Advanced stage follicular lymphoma (FL) is incurable by conventional therapies. In the present pilot clinical trial, we explored the efficacy and immunogenicity of a novel in situ immunotherapeutic strategy. Fourteen patients with untreated or relapsed stage III/IV FL were included and received local radiotherapy to solitary lymphoma nodes and intranodal injections of low-dose rituximab (5 mg), immature autologous dendritic cells, and granulocyte-macrophage colony-stimulating factor at the same site. The treatment was repeated 3 times targeting different lymphoma nodes. Primary end points were clinical responses and induction of systemic immunity. Five out of 14 patients (36%) displayed objective clinical responses, including 1 patient with cutaneous FL who showed regression of skin lesions. Two of the patients had durable complete remissions. Notably, the magnitude of vaccination-induced systemic CD8 T-cell-mediated responses correlated closely with reduction in total tumor area (r = 0.71, P = .006), and immune responders showed prolonged time to next treatment. Clinical responders did not have a lower tumor burden than nonresponders pretreatment, suggesting that the T cells could eliminate large tumor masses once immune responses were induced. In conclusion, the combined use of 3 treatment modalities, and in situ administration in single lymphoma nodes, mediated systemic T-cell immunity accompanied by regression of disseminated FL. The trial was registered at www.clinicaltrials.gov as #NCT01926639., (© 2015 by The American Society of Hematology.)

Unlabelled: Because only pathologic examination can confirm the presence or absence of malignant disease in cancer patients, a certain rate of misinterpretation in any kind of imaging study is inevitable. For the accuracy of interpretation to be improved, determination of the nature, causes, and magnitude of this problem is needed. This study was designed to collect pertinent information from physicians referring patients for oncologic (18)F-FDG PET/CT., Methods: A total of 662 referring physicians completed an 11-question survey focused on their experience with the interpretation of oncologic (18)F-FDG PET/CT studies. The participants were oncologists (36.1%; n = 239), hematologists (14.5%; n = 96), radiation oncologists (7.4%; n = 49), surgeons (33.8%; n = 224), and other physicians (8.2%; n = 54). Questions were aimed at determining the frequency, nature, and causes of scan misinterpretations as well as potential solutions to reduce the frequency of misinterpretations., Results: Perceived misinterpretation rates ranged from 5% to 20%, according to most (59.3%) of the participants; 20.8% of respondents reported rates of less than 5%. Overinterpretation rather than underinterpretation was more frequently encountered (68.9% vs. 8.7%, respectively). Limited availability of a patient's history and limited experience of interpreters were the major contributors to this phenomenon, according to 46.8% and 26.7% of the participants, respectively. The actions most commonly suggested to reduce misinterpretation rates (multiple suggestions were possible) were the institution of multidisciplinary meetings (59.8%), the provision of adequate history when ordering an examination (37.4%), and a discussion with imaging specialists when receiving the results of the examination (38.4%)., Conclusion: Overinterpretation rather than underinterpretation of oncologic (18)F-FDG PET/CT studies prevails in clinical practice, according to referring physicians. Closer collaboration of imaging specialists with referring physicians through more multidisciplinary meetings, improved communication, and targeted training of interpreting physicians are actions suggested to reduce the rates of misinterpretation of oncologic (18)F-FDG PET/CT studies., (© 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Unlabelled: Anti-1-amino-3-(18)F-fluorocyclobutane-1-carboxylic acid ((18)F-FACBC) is a synthetic amino acid analog PET radiotracer undergoing clinical trials for the evaluation of prostate and other cancers. We aimed to describe common physiologic uptake patterns, incidental findings, and variants in patients who had undergone (18)F-FACBC PET., Methods: Sixteen clinical trials involving 611 (18)F-FACBC studies from 6 centers, which included dosimetry studies on 12 healthy volunteers, were reviewed. Qualitative observations of common physiologic patterns, incidental uptake, and variants that could simulate disease were recorded and compared with similar observations in studies of the healthy volunteers. Quantitative analysis of select data and review of prior published reports and observations were also made., Results: The liver and pancreas demonstrated the most intense uptake. Moderate salivary and pituitary uptake and variable mild to moderate bowel activity were commonly visualized. Moderate bone marrow and mild muscle activity were present on early images, with marrow activity decreasing and muscle activity increasing with time. Brain and lungs demonstrated activity less than blood pool. Though (18)F-FACBC exhibited little renal excretion or bladder uptake during the clinically useful early imaging time window, mild to moderate activity might accumulate in the bladder and interfere with evaluation of adjacent prostate bed and seminal vesicles in 5%-10% of patients. Uptake might also occur from benign processes such as infection, inflammation, prostatic hyperplasia, and metabolically active benign bone lesions such as osteoid osteoma., Conclusion: Common physiologic uptake patterns were similar to those noted in healthy volunteers. The activity in organs followed the presence of amino acid transport and metabolism described with other amino acid-based PET radiotracers. As with other PET radiotracers such as (18)F-FDG, focal nonphysiologic uptake may represent incidental malignancy. Uptake due to benign etiologies distinct from physiologic background also occurred and could lead to misinterpretations if the reader is unaware of them., (© 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

The main objective of the MCL3 study was to improve outcome for patients not in complete remission (CR) before transplant by adding (90)Y-ibritumomab-tiuxetan (Zevalin) to the high-dose regimen. One hundred sixty untreated, stage II-IV mantle cell lymphoma patients <66 years received rituximab (R)-maxi-CHOP (cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone) alternating with R-high-dose cytarabine (6 cycles total), followed by high-dose BEAM/C (bis-chloroethylnitrosourea, etoposide, cytarabine, and melphalan or cyclophosphamide) and autologous stem cell transplantation from 2005 to 2009. Zevalin (0.4 mCi/kg) was given to responders not in CR before transplant. Overall response rate pretransplant was 97%. The outcome did not differ from that of the historic control: the MCL2 trial with similar treatment except for Zevalin. Overall survival (OS), event-free survival (EFS), and progression-free survival (PFS) at 4 years were 78%, 62%, and 71%, respectively. For responding non-CR patients who received Zevalin, duration of response was shorter than for the CR group. Inferior PFS, EFS, and OS were predicted by positron emission tomography (PET) positivity pretransplant and detectable minimal residual disease (MRD) after transplant. In conclusion, positive PET and MRD were strong predictors of outcome. Intensification with Zevalin may be too late to improve the outcome of patients not in CR before transplant. This trial was registered at www.clinicaltrials.gov as #NCT00514475.

Aim: To elucidate techniques most commonly used for interpreting oncologic PET/CT studies. This survey forms a basis to work on standardization of reporting and highlight the most important issues to be addressed., Methods: A web-based survey of 329 PET/CT imaging specialists was designed with the intent to determine image interpretation patterns. The questionnaire consisted of 19 questions. Of the 329 participants, 230 were nuclear medicine specialists, 46 were radiologists, and 53 had dual-board certification., Results: Report ofstandardized uptake values (SUV) is not consistent;only50.2% of respondents always report SUVs, while 45.2% report only if needed or requested. 80.9% of respondents indicated that reporting of SUV is only appropriate when its limitations are understood whereby a large majority prefer to report SUVmax. Maximum intensity projection (MIP) images are almost always reviewed by 91.1% of the respondents. An accurate and detailed clinical history is considered an essential element for reading PET/CT studies by 84.0%, but only 20.7% report that this is always available. The most common self-reported average time for reviewing and reporting of whole body PET/CT (with no prior comparison scan) was 15-20 min (27.5%)., Conclusion: PET readers have considerable reservations regarding the use and reporting of SUVs. SUVmax is more frequently used than SUVmean. Evaluation of MIP images is considered an important element of PET/CT interpretation. Although availability of sufficient patient's history is considered essential, this is rarely available.

Objective: The aim of the study was to investigate a new principle for collimation of gamma probes for radioguided surgery and sentinel node detection: the use of asymmetric lateral shielding. The intension was to maintain the sensitivity in the lateral and forward directions on the unshielded side while at the same time to shield the probe against high activity sources that could mask the signal from the object to be detected., Methods: The device was constructed to shield only against photons that come from a region in space that spans approximately 180° sideways and forwards relative to the detector. The intension of the study was to demonstrate the principle rather than to document its use in the clinic. Sensitivity profiles were derived from measurements obtained while stepwise moving the probe relatively to a point source of known activity surrounded by water. The measurements were taken in the symmetry plane of the collimator where the shielding effects were expected to be most pronounced., Results: The asymmetric collimator led to nearly unchanged sensitivity in the lateral and forward directions. At the same time, the field of view was effectively shrunk on the shielded side. Contributions from sources lateral and close to the shield were reduced by factors up to 45., Conclusion: By rotating the probe around its longitudinal axis, an asymmetric add-on shield collimator could potentially make it easier to detect a sentinel node when this is located close to a neighbouring high activity region like the urinary bladder or the injection site., (© 2013 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.)

Background: Respiratory gating in positron emission tomography (PET) is used to improve detection of small tumors in the lower lung regions and in the liver, and to obtain a better estimate of the standardized uptake value (SUV)., Purpose: To develop a time-efficient method for acquisition of respiratory-gated PET/CT that would produce one single high quality image volume corresponding to a breath-hold state., Material and Methods: An instrument was developed that displayed to the patient either red or green numbers, counting down from a chosen maximum to one at a rate of one dial per second. The patient was instructed to repeatedly hold the breath in moderate inspiration when red numbers were displayed and to breathe freely during display of green numbers. PET data were acquired in list mode and trigger signals were sent to the scanner and inserted into the list file each time the color of the countdown numbers switched from green to red. Data acquired during breath-holds were used to create one single image volume., Results: High quality breath-hold images were obtained from 10 min data acquisition at one bed position. Improved image quality compared to standard whole-body PET was demonstrated by a significant reduction of noise (standard deviation) in regions of normal liver tissues., Conclusion: The instruction to perform repeated breath-holds was well understood by patients and they cooperated satisfactorily. When the new procedure is used the duration of the data acquisition may typically be reduced by a factor of 4 compared to conventional respiratory-gated protocols where the patient breathes freely.

Introduction: Our primary aim was to make a phantom for PET that could mimic a highly irregular tumour and provide true tumour contours. The secondary aim was to use the phantom to assess the accuracy of different methods for delineation of tumour volume from the PET images., Material and Methods: An empty mould was produced on the basis of a contrast enhanced computed tomography (CT) study of a patient with a squamous cell carcinoma in the head and neck region. The mould was filled with a homogeneous fast-settling gel that contained both (18)F for positron emission tomography (PET) and an iodine contrast agent. This phantom (mould and gel) was scanned on a PET/CT scanner. A series of reference tumour contours were obtained from the CT images in the PET/CT. Tumour delineation based on the PET images was achieved manually, by isoSUV thresholding, and by a recently developed three-dimensional (3D) Difference of Gaussians algorithm (DoG). Average distances between the PET-derived and reference contours were assessed by a 3D distance transform., Results: The manual, thresholding and DoG delineation methods resulted in volumes that were 146%, 86% and 100% of the reference volume, respectively, and average distance deviations from the reference surface were 1.57 mm, 1.48 mm and 1.0, mm, respectively., Discussion: Manual drawing as well as isoSUV determination of tumour contours in geometrically irregular tumours may be unreliable. The DoG method may contribute to more correct delineation of the tumour. Although the present phantom had a homogeneous distribution of activity, it may also provide useful knowledge in the case of inhomogeneous activity distributions., Conclusion: The geometric irregular tumour phantom with its inherent reference contours was an important tool for testing of different delineation methods and for teaching delineation.

Unlabelled: Oncologic (18)F-FDG PET/CT is rapidly gaining acceptance in clinical practice. However, the referring physician's attitude toward the usefulness of this diagnostic modality is unknown. This survey was undertaken to collect information regarding the current perspective of referring physicians on oncologic PET/CT., Methods: We conducted a prospective worldwide, Web-based survey of physicians who manage cancer patients. A total of 963 referring physicians completed a 20-question survey focused on their experience with oncologic (18)F-FDG PET/CT. Attention was directed toward their confidence about indications, their satisfaction with related educational resources, the quality of interaction with interpreting physicians, and practical problems encountered. The respondents included oncologists (38.5%, n = 371), hematologists (16.4%, n = 158), radiation oncologists (9.0%, n = 87), surgeons (30.3%, n = 292), and other physicians (5.7%, n = 55)., Results: Only 25.2% of respondents considered the oncologic (18)F-FDG PET/CT indications to be well established and defined. Frequent uncertainty about the need for a PET scan was indicated by 62.3% of the respondents. High cost and overinterpretation of findings were the most commonly reported concerns (47.0% and 40.9%, respectively). The experience and skill level of the interpreting physician was considered very important by 96.8% of the surveyed physicians., Conclusion: Referring physicians expressed considerable uncertainty about the appropriate use of oncologic PET/CT. Additional major concerns are procedure costs and quality of interpretation. The responses suggest a strong need for efforts to educate referring and interpreting physicians about the appropriate use of (18)F-FDG PET/CT in oncology.

Differentiated thyroid cancer (DTC) is a rare cancer with excellent prognosis for most patients. Primary treatment is surgery. Adjuvant radioiodine is used after surgery and in case of residual radioiodine positive disease. Measurements of serum thyroglobulin levels and neck ultrasound (US) are the primary follow-up procedures. For suspected recurrence, US, computed tomography (CT), radioiodine single photon emission computed tomography/CT, and FDG positron emission tomography/CT will be appropriate choices for restaging and further treatment planning. Multidisciplinary collaboration is crucial for optimal management of patients with DTC.

Objective: During a short period of 10 days, four patients presented with intense extraosseous uptake of a technetium-labelled bone-seeking agent, three in the heart and one in the liver at our hospital. During the next 6 weeks, identical heart uptake was found in another two patients. Two patients were re-examined, with identical uptake on the second occasion. A search for a possible cause was initiated., Methods: Bone scintigraphy with Teceos(®) was performed after labelling the kit as described in the Summary of Product Characteristics [IBA, http://www.iba-molecular.com/sites/default/files/spcT1901E.pdf (in french, 29/3/2011)]. On two occasions, the kit used was retrospectively analysed, without any apparent abnormality. Two patients were re-examined 1 month later, with identical cardiac and liver uptake on repeat examination. Contact with referring physicians and blood test screening did not show any consistent reason for these extraosseous uptakes. Additionally, five cases at other hospitals in Norway have been brought to our attention., Results: In at least ten patients, intense cardiac uptake has been recorded, all in relatively old patients, and one young patient had massive liver uptake. No abnormalities in labelling or composition of 3,3-diphospho-1,2-propanedicarboxylic acid were found., Discussion: Liver and cardiac uptakes of bone-seeking agents have been described in amyloidosis, and for the heart, after myocardial infarction. We have ruled out any possible contamination by interfering radiopharmaceuticals and cannot find any reason for these findings. Eleven patients with amyloidosis seem one of several hypotheses that is highly improbable., (© 2011 The Authors. Clinical Physiology and Functional Imaging © 2011 Scandinavian Society of Clinical Physiology and Nuclear Medicine.)

Objective: To explore the prognostic value of F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) in radioiodine-negative patients with differentiated follicular cell-derived thyroid carcinoma with circulating antithyroglobulin autoantibodies (TgAb)., Methods: We retrospectively reviewed cases of all patients with differentiated thyroid cancer and increased TgAb referred for FDG-PET at Mayo Clinic, Rochester, Minnesota, from August 2001 to December 2004. PET findings were compared with results of other imaging and laboratory studies. Follow-up information was recorded until 19 December 2009., Results: Of the 17 patients identified, PET results were true positive in 10 and false negative in two. In eight of these 12 patients with confirmed residual or recurrent disease, the increased TgAb level persisted and the disease progressed. In four of the 12 patients, TgAb decreased or disappeared after further treatment. In five patients, no residual or recurrent disease was found during follow-up. PET results were true negative in these five patients; TgAb disappeared spontaneously in four of these patients., Conclusions: Negative PET results were associated with the absence of active disease and disappearing TgAb over time. FDG-avid residual lesions were associated with more aggressive disease and persistently increased TgAb.

Purpose: To explore the prognostic value of 2-deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography (PET) in patients with suspected residual or recurrent medullary thyroid carcinoma (MTC)., Procedures: This retrospective study included all patients with MTC examined with FDG-PET at Mayo Clinic, Rochester, Minnesota, from October 1999 to March 2008. The PET results were compared with other imaging studies and clinical findings, including carcinoembryonic antigen and calcitonin levels., Results: Twenty-nine patients with MTC were included. PET was positive in 14 patients, with follow-up information for 11; six died from metastatic disease, four had disease progression, and one remained in stable condition. PET was negative in 15 patients, with follow-up for 12; one had recurrent disease, and 11 had no evidence of clinical disease. Calcitonin doubling time was shorter for PET-positive than for PET-negative patients., Conclusion: FDG-PET has high prognostic value in patients with suspected residual or recurrent MTC.

An abdomen phantom, containing an idealised fillable liver volume was developed. A fast settling gel was used to produce a row of simulated tumours as well as normal surrounding tissue, each of these components containing different concentrations of (18)F-FDG. The magnitude of the signal above normal tissue intensity as well as the noise was obtained after reconstructions with Ordered Subset expectation-maximization (OSEM) and various Gaussian smoothing filters. Signals derived by 'simulated intensity diffusion' agreed well with experimental results.

Background. The purpose of this work was to study clinical and histopathological tumor characteristics of patients treated for synchronous or metachronous skeletal osteosarcoma at The Norwegian Radium Hospital from January 1, 1980 to January 1, 2008. Patients and methods. The hospital sarcoma database and patient records were reviewed to identify cases with synchronous or metachronous skeletal osteosarcoma. Patients with more than one skeletal lesion in the absence of pulmonary or other soft tissue tumor manifestations were included in the study, and histopathological slides from these tumors were reviewed. Results. Among a total of 297 registered osteosarcoma patients, six with synchronous (2.0%) and 10 with metachronous (3.4%) skeletal osteosarcomas were identified. All tumors were of high-grade malignancy. Treatment at the time of the first osteosarcoma diagnosis was in most cases wide resections and multi-agent chemotherapy according to international protocols, whereas the treatment for metachronous tumors was individualized and in general much less intensive. One patient was diagnosed with Li-Fraumeni syndrome, two other individuals may be suspected to have the same syndrome, and yet another patient had previously been treated for a bilateral retinoblastoma. Thirteen patients are dead, 11 from metastatic osteosarcoma, one from myelodysplastic syndrome, and one from wound infection and methotrexate-related nephrotoxicity; whereas three patients are still alive with no evidence of osteosarcoma. Conclusions. The prognosis for patients with synchronous and metachronous skeletal osteosarcoma is poor. However, because long-term survival is seen, aggressive treatment to selected cases, e.g., patients with an osteosarcoma predisposing syndrome and/or late occurring metachronous tumours, is justified. Revealing a possible clonal relationship between these tumors, e.g., by karyotyping, may be of interest for estimating prognosis and guide therapy intensiveness.

Objective: Integrin scintimammography with NC100692 and a dedicated gamma-camera, LumaGEM, based on semi-conductor technology, was performed to investigate the detection ability of this combination in breast cancer., Methods: Eight patients with a high suspicion of breast cancer were administered 600-750 MBq (99m)Tc-labelled NC100629. Two acquisitions using a cranio-caudal and a lateral view were used, with moderate compression of the breast., Results: LumaGEM scintigraphy revealed 9 of 11 malignancies, sized 6-20 mm. Two lesions in patients with multicentric disease were not diagnosed, one of which measured only 2.5 mm. In one patient, the procedure was inconclusive, due to major breast hypertrophy., Conclusion: The combined use of NC100629 and a dedicated gamma-camera for breast imaging was highly effective in diagnosing breast cancer.

Background: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive solid tumors in humans. The use of positron emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG) in ATC has not been studied, and only a few case reports have been published. The objective of this study was to investigate the potential contribution of 18F-FDG PET to the clinical management of patients with ATC., Methods: All patients with ATC studied with 18F-FDG PET from August 2001 through March 2007 were included. The PET results were correlated with computed tomography, ultrasound, magnetic resonance imaging, bone scan, histology, and clinical follow-up. The FDG uptake was semiquantified as maximum standard uptake value. Any change in the treatment plan as a direct result of the PET findings as documented in the clinical notes was recorded., Results: Sixteen patients were included. True-positive PET findings were seen for all primary tumors, in all nine patients with lymph node metastases, in five out of eight patients with lung metastases, and in two patients with distant metastases other than lung metastases. In 8 of the 16 patients, the medical records reported a direct impact of the PET findings on the clinical management., Conclusions: ATC demonstrates intense uptake on 18F-FDG PET images. In 8 of the 16 patients (50%), the medical records reported a direct impact of the PET findings on the management of the patient. PET may improve disease detection and have an impact on the management of patients with ATC relative to other imaging modalities.

The aim of this study was to assess the diagnostic utility of thyroglobulin (Tg) in fine needle aspirates (Tg-FNAB) of nonthyroidal neck masses using a sensitive in-house method for detecting Tg in washout specimens. A total of 256 samples from 145 patients were evaluated for Tg in washout specimen from FNAB and compared to corresponding cytological smear and histology of 46 surgical specimens. Tg was measured by a sensitive in-house time-resolved immunofluorometric assay. The sensitivity for Tg-FNAB alone or in combination with cytological findings was found to be 100% in both the follow-up group and before primary surgery. In the follow-up group the specificity of Tg-FNAB was 100%. Fifty-nine of 60 follow-up specimens with malignant cytology were Tg-FNAB positive (n = 195). Histological examination of one lymph node with malignant cytology and negative Tg-FNAB showed metastasis from carcinoma of the salivary gland. Tg-FNAB was positive in 25 specimens with suspicious or cystic cytology. Tg-FNAB values were high (median 4557 microg/l, range 122-37200 microg/l) in washout specimen from cystic metastasis from which cytology did not confirm malignancy. Of the 20 lymph nodes with histology confirming metastasis from differentiated thyroid carcinoma (DTC), the Tg-FNAB was positive in 19 and intermediate in one. However, before primary surgery, two Tg-FNABs were false positive compared to the histology of the lymph nodes. TgAb in serum did not interfere with FNAB-Tg measurements. Tg-FNAB measurement is accurate with high sensitivity (100%) and of great importance in detecting cystic metastasis when cytology is not conclusive. Even metastases to small neck lymph nodes may be detected by using sensitive Tg-assay. Serum thyroglobulin antibodies appear to have ignorable effect on the clinical performance of Tg-FNAB., (Copyright 2007 Wiley-Liss, Inc.)

Unlabelled: Our purpose was to determine the clinical significance of diffusely increased (18)F-FDG uptake in the thyroid gland as an incidental finding on PET/CT., Methods: All patients who were found to have diffuse thyroid uptake on (18)F-FDG PET/CT in our institution between November 2004 and June 2006 were investigated and compared with an age- and sex-matched control group. The (18)F-FDG uptake in the thyroid was semiquantified using maximum standardized uptake value and correlated to the available serum thyroid-stimulating hormone (TSH) and thyroid peroxidase (TPO) antibody levels using regression analysis., Results: Of the 4,732 patients, 138 (2.9%) had diffuse thyroid uptake. Clinical information was available for 133 of the 138 patients. Sixty-three (47.4%) had a prior diagnosis of hypothyroidism or autoimmune thyroiditis, of whom 56 were receiving thyroxine therapy. In the control group, consisting of 133 patients with no thyroid uptake, there were 13 (9.8%) with a prior diagnosis of hypothyroidism, 11 of whom were receiving thyroxine therapy. In the study group, 38 (28.6%) of 133 patients did not undergo any further investigation for thyroid disease, whereas 32 (24.1%) of 133 patients were examined for thyroid disease after PET. Nineteen were found with autoimmune thyroiditis or hypothyroidism, and replacement therapy was initiated in 12. No significant correlation was found between maximum standardized uptake value and TSH (P = 0.09) or TPO antibody (P = 0.68) levels., Conclusion: The incidental finding of increased (18)F-FDG uptake in the thyroid gland is associated with chronic lymphocytic (Hashimoto's) thyroiditis and does not seem to be affected by thyroid hormone therapy. SUV correlated neither with the degree of hypothyroidism nor with the titer of TPO antibodies.