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Aim: Kinase inhibitors have been proposed as novel therapeutic agents in different forms of solid tumours. The Food and Drug Administration (FDA) approved the use of Sorafenib, an oral multikinase inhibitor, for advanced renal carcinoma and unresectable hepatocellular carcinoma. On-going studies are investigating the efficacy of Sorafenib in other solid tumours such as melanoma and non-small cells lung carcinoma and pre-clinical models showed the efficacy of treatment with Sorafenib in murine models of renal cells carcinoma, breast cancer, colon carcinoma and melanoma. To our knowledge, Sorafenib has never been employed in human lymphoma. The aim of the present study was to assess the efficacy of Sorafenib in murine models of human anaplastic large cells lymphoma (ALCL) and Hodgkin lymphoma (HD)., Methods: Sorafenib cytotoxicity was assessed in vitro and growth inhibition (IC50) was calculated. Cells were assayed for Caspase-3 to measure apoptosis. Human ALCL and HD xenografts in NOD/SCID mice were monitored by small animal positron emission tomography (PET) and computed tomography (CT) over time. Tumour bearing animals were randomly selected to receive treatment with Sorafenib or no treatment. Pathology was available in all cases., Results: Sorafenib efficacy on cells proliferation and apoptosis (IC50: HD=0.0343 mg/L; ALCL=0.319 mg/L) was confirmed in vitro. Caspase-3 production showed a dose-dependent trend reaching significantly higher values for 0.046 mg/L and 0.465 mg/L drug concentrations in both cell lines. In vivo experiments showed a progressive increase of tumour lesions metabolism and dimensions regardless treatment., Conclusion: Sorafenib showed a good cytotoxic effect in vitro especially on human HD cell line, but these findings were not confirmed in vivo. The strong discrepancy between in vitro and in vivo results suggests that further studies are needed to better acknowledge the biodistribution and metabolism of Sorafenib in NOD/SCID mice. Factors influencing drug availability at tumour site or differences in the downstream pathways may be responsible for the scarse effect of treatment.

Purpose: To retrospectively evaluate the sensitivity, specificity and accuracy of (68)Ga-DOTA-NOC PET/CT and CT alone for the evaluation of bone metastasis in patients with neuroendocrine tumour (NET)., Methods: From among patients with NET who underwent (68)Ga-DOTA-NOC PET/CT between April 2006 and November 2008 in our centre, 223 were included in the study. Criteria for inclusion were pathological confirmation of NET and a follow-up period of at least 10 months. PET and CT images were retrospectively reviewed by two nuclear medicine specialists and two radiologists, respectively, without knowledge of the patient history or the findings of other imaging modalities. PET data were compared with the CT findings. Interobserver agreement was evaluated in terms of the kappa score. Clinical and imaging follow-up were used as the standard of reference to evaluate the PET findings., Results: PET was performed for staging (49/223), unknown primary tumour detection (24/223), restaging (32/223), restaging before radioimmunotherapy (1/223), evaluation during therapy (12/223), equivocal findings on conventional imaging (4/223 at the bone level; 61/223 at sites other than bone), and follow-up (40/223). A very high interobserver agreement was observed. CT detected at least one bone lesion in only 35 of 44 patients with a positive PET scan. In particular, PET showed more lesions in 20/35 patients, a lower number of lesions in 8/35, and the same number in 7/35. The characteristics of the lesions (sclerotic, lytic, mixed) on the basis of the CT report did not influence PET reading. PET revealed the presence of at least one bone metastasis in nine patients with a negative CT scan. Considering patients with a negative PET scan (179), CT showed equivocal findings at the bone level in three (single small sclerotic abnormality in two at the spine level, and bilateral small sclerotic abnormalities in the humeri, femurs and scapula). Clinical follow-up confirmed the PET findings in all patients; thus there were no false-positive or false-negative findings. Considering all patients, PET detected more lesions than CT (246 vs. 194). As compared to CT, on a patient basis PET showed a higher sensitivity (100% vs. 80%), specificity (100% vs. 98%), positive predictive value (100% vs. 92%), and negative predictive value (100% vs. 95%)., Conclusion: In conclusion, (68)Ga DOTA-NOC PET was more accurate than CT for the identification of bone lesions and led to a change in clinical management in nine patients with a negative CT scan.

Neuroendocrine tumours (NET) diagnosis has represented a major challenge in the past decades. The introduction of somatostatin receptor scintigraphy in the diagnostic work-up led to a significant improvement of accuracy. However with the advent of positron emission tomography (PET) that presents a higher spatial resolution as compared to the gamma camera and an array of different radiotracers, it is now possible to image NET with an even higher accuracy. In fact, PET imaging of NET is a rapidly evolving field closely connected to the development of novel beta-emitting radiopharmaceuticals. NET can be easily visualized on PET scans using an array of both metabolic and receptor-based tracers. [18F]DOPA and [68Ga]DOTA-peptides (DOTA-TOC, DOTA-NOC, DOTA-TATE) are very promising to image well differentiated NET and were reported to be superior to other imaging modalities (computed tomography [CT], somatostatin receptor scintigraphy). On the contrary, the role of [18F]FDG is limited in well differentiated NET, due to their low glucose metabolism and growth rate, while it still can provide valuable information in less differentiated tumours. On-going studies are investigating the potential role of new imaging agents (bombesin, GLP-1, CCK) that specifically bind to receptors expressed on NET cells.

Fluoro-deoxy-glucose positron emission tomography (FDG PET) has largely been used for response assessment after treatment of lymphoma, resulting in a very sensitive and specific imaging technique for the detection of residual disease. For this reason FDG PET has recently been proposed to be integrated in the International Workshop Criteria. In this report, a patient with non-Hodgkin lymphoma was treated with radioimmunotherapy for disease relapse, demonstrated by PET. Post-treatment evaluation was performed 9 weeks after treatment, and PET showed almost complete disappearance of tracer uptake, but with faint persistence of uptake at 1 iliac node and thus was a suspect for residual disease. However, a wait-and-see approach was decided and the patient was rescanned with PET 18 weeks after treatment, and the results were finally negative. This case indicates that after completion of radioimmunotherapy it may be recommended to wait several weeks before performing a PET scan and, in case of minimal findings, to consider a short-term re-evaluation.

Purpose of the Report: We assessed the usefulness of F-18 fluorodeoxyglucose positron emission tomography (FDG PET) and C-11 acetate PET (AC PET) in distinguishing hepatic lesions due to consequential disease (hepatocellular adenoma and malignant lesions) from focal nodular hyperplasia (FNH) in patients at low risk of malignancy., Materials and Methods: Thirty-one patients with 43 lesions were prospectively enrolled. The diagnostic work-up included Doppler and contrast-enhanced ultrasonography, contrast-enhanced computed tomography, and/or magnetic resonance imaging. Fine needle biopsy was performed if the imaging study was inconclusive. The work-up revealed 36 FNH and 7 consequential lesions (5 hepatocellular adenoma, 1 hepatoma, and 1 metastasis). All patients underwent FDG and AC PET. FDG PET with target/background ratio (T/Br) greater than 1.2 and AC PET with T/Br of less than 1.2 were considered positive test for consequential disease., Results: On FDG PET, we had 6 true-positive out of 7 lesions due to consequential diseases, with a sensitivity of 85.7%, and 33 true-negative out of 36 lesions with FNH, with a specificity of 91.7%. Using AC PET, there were 2 true-positive lesions out of 7 caused by neoplasms, with a sensitivity of 28.6%, and 34 true-negative lesions out of 36 FNH, with a specificity of 94.4%., Conclusions: When the goal is differentiating FNH from liver neoplasms, AC PET offered no additional diagnostic advantage over what is achieved with FDG PET.

Positron emission tomography (PET) is routinely performed in patients with cancer for disease staging, assessment of relapse, and evaluation of therapy response. In addition to its well-established value in human malignant diseases, the use of special small animal PET (SA-PET) scanners have allowed for accurate assessment of small animals bearing human tumors. This application of PET provides whole-body, noninvasive, functional data of tumor lesions and can be used to assess abnormalities in the metabolic pathways of cancer, such as uncontrolled proliferation, increased apoptosis, and angiogenesis. Several positron-emitting tracers labeled with 18-fluorine and 11-carbon are currently available for PET studies to image abnormal biologic pathways of tumors. Moreover, SA-PET can be used to evaluate tumor-cell-receptor expression, a sign of tumor cells differentiation that is relevant for planning targeted therapies. Another advantage of SA-PET is the quantitation capability: Semiquantitation of the tumor activity can be performed at each scan and compared in the same animal over time to monitor tumor growth or to assess the response to new therapies. This review focuses on the applications of SA-PET for the visualization of the pathophysiologic pathways of tumor cells.

In recent years, new technologies have become available for imaging small animals. The use of animal models in basic and preclinical sciences, for example, offers the possibility of testing diagnostic markers and drugs, which is becoming crucial in the success and timeliness of research and is allowing a more efficient approach in defining study objectives and providing many advantages for both clinical research and the pharmaceutical industry. The use of these instruments offers data that are more predictive of the distribution and efficacy of a compound. The mouse, in particular, has become a key animal model system for studying human disease. It offers the possibility of manipulating its genome and producing accurate models for many human disorders, thus resulting in significant progress in understanding pathologenic mechanisms. In neurobiology, the possibility of simulating neurodegenerative diseases has enabled the development and validation of new treatment strategies based on gene therapy or cell grafting. Noninvasive imaging in small living animal models has gained increasing importance in preclinical research, itself becoming an independent specialty. The aim of this article is to review the characteristics of these systems and illustrate their main applications.

The role of F-18-fluorodeoxyglucose positron emission tomography (FDG-PET) in the assessment of lymphoma patients is well established, and PET is routinely used for initial staging, early evaluation of treatment response, and identification of disease relapse. The early evaluation of response to therapy (interim PET) has been reported to be an accurate predictor of progression-free survival, and end-treatment PET has been suggested to be unnecessary if interim PET results are negative. We report on a patient with Hodgkin's disease with a positive PET scan at presentation and a negative interim PET (carried out after three cycles of adriamycin, bleomycin, vinblastine, and dacarbazine; ABVD). Despite uncomplicated clinical course, end-treatment PET (following six cycles) was positive, showing a very early relapse. For this reason, patient underwent further treatment; however, a complete remission was not obtained, and a poor prognosis is expected. This case testifies the possibility of early relapse of lymphoma even in the case of negative interim PET; it also supports the usefulness of end-treatment PET scan in lymphoma patients.

With increasing application of positron-emission tomography (PET) imaging, familiarity with the applications of PET in genitourinary oncology, especially prostate-cancer (PCa) imaging, becomes important. PET studies provide functional information using radiolabeled tracers, with fluoro-dexoxy-glucose (FDG) being the most commonly used. Nevertheless FDG has limitations for evaluation of PCa patients and therefore alternative tracers are being investigated. To date, the best results have been obtained with 11C-choline and 11C-acetate PET, which seem to demonstrate similar values in this field. We review the current role of PET in PCa patients based on data published in the literature as well as our own experience. Most studies of PET imaging of PCa address three goals: a) detecting primary PCa; b) staging PCa; and c) assessing PCa recurrence. From available results, routine clinical use of 11C-choline PET cannot be recommended for detecting and staging primary PCa. At present, the only clinical indication for imaging PCa with 11C-choline-PET is evaluation of suspected recurrence after treatment.

Background: Small-animal imaging has become a relevant research field in pre-clinical oncology. In particular, metabolic information provided by small-animal positron emission tomography (PET) is very useful to closely monitor tumour growth and assess therapy response in murine models of human disease. There are various murine models for human lung adenocarcinoma, but those for squamous cell lung carcinoma, the most common form of human cancer, are lacking., Aim: To assess the feasibility of 18F-FDG small-animal PET to monitor tumour growth in a chemically induced model of squamous cell carcinoma of the lung., Materials and Methods: Nineteen NIH Swiss mice were skin painted by N-nitroso-tris-chloroethylurea (NTCU) twice a week, with a 3 day interval, for 8 months and 10 NIH Swiss mice skin painted with NTCU solvent (acetone) were used as controls. 18F-FDG PET was performed under sevofluorane anaesthesia and oxygen supplementation at 2, 4, 6 and 8 months from initial treatment. Images were assessed by visual analysis and semi-quantitatively. When a diffuse distribution of tumour was noted, the mean of the counts/pixel measured at three lung levels, corrected for the effective dose injected and for decay, was used for comparison between mutagen-painted and control mice. Pathological evaluation was carried out from the time of the first positive PET results in a subgroup of the whole population to assess correlation with PET findings. Small animal CT was performed at 8 months in another subgroup., Results: In both terms of visual analysis and measurement of total lung activity, 18F-FDG PET at 2 and 4 months from initial treatment were comparable in mutagen-painted and controls. At 6 months, PET images showed a faint and diffuse uptake over both lung fields in mutagen-painted mice with multiple focal areas of increased tracer uptake that merged into confluent masses at 8 months and seriously subverting lung architecture on computed tomography. Total lung activity was significantly higher in mutagen-painted versus control mice at 6 (P=0.00000668) and 8 months (P=0.00000043) from initial treatment and paralleled the progressive lung involvement and histological severity., Conclusions: 18F-FDG PET may be useful in the assessment of this chemically induced murine model of lung squamous cells carcinoma. The total lung activity may be used as a measure of tumour metabolic activity of the tumour-bearing animals and may be useful in new drug testing studies.

Background and Aim: Small-animal PET is acquiring importance for pre-clinical studies. In rodents, radiotracers are usually administrated via the tail vein. This procedure can be very difficult and time-consuming as soft tissue extravasations are very frequent and tail scars can prevent repeated injections after initial failure. The aim of our study was to compare the retro-orbital (RO) versus tail vein intravenous (i.v.) administration of (18)F-FDG and (11)C-choline in mice for small-animal PET studies., Methods: We evaluated four healthy female ICR CD1 mice according to the following protocol. Day 1: each animal underwent an i.v. injection of 28 MBq of (11)C-choline. PET scan was performed after 10 min and 40 min. Day 2: each animal received an RO injection of 28 MBq of (11)C-choline. A PET scan was performed after 10 min and 40 min. Day 3: each animal received an i.v. injection of 28 MBq of (18)F-FDG. A PET scan was performed after 60 min and 120 min. Day 4: each animal received an RO injection of 28 MBq of (18)F-FDG. A PET scan was performed after 60 min and 120 min. Administration and image acquisition were performed under gas anaesthesia. For FDG studies the animals fasted for 2 h and were kept asleep for 20-30 min after injection, to avoid muscular uptake. Images were reconstructed with 2-D OSEM. For each scan ROIs were drawn on liver, kidneys, lung, brain, heart brown fat and muscles, and the SUV was calculated. We finally compared choline i.v. standard acquisition to choline RO standard acquisition; choline i.v. delayed acquisition to choline RO delayed acquisition; FDG i.v. standard acquisition to FDG RO standard acquisition; FDG i.v. delayed acquisition to FDG RO delayed acquisition., Results: The RO injections for both (18)F-FDG and (11)C-choline were comparable to the intravenous injection of F-FDG for the standard and delayed acquisitions., Conclusion: The RO administration in mice represents a technical advantage over intravenous administration in being an easier and faster procedure. However, its use requires high specific activity while its value in peptides and other receptor-specific radiopharmaceuticals needs further assessment.

Background: Multiple Myeloma (MM) is a B cell neoplasm causing lytic or osteopenic bone abnormalities. Whole body skeletal survey (WBSS), Magnetic resonance (MR) and 18F-FDG PET/CT are imaging techniques routinely used for the evaluation of bone involvement in MM patients., Aim: As MM bone lesions may present low 18F-FDG uptake; the aim of this study was to assess the possible added value and limitations of 11C-Choline to that of 18F-FDG PET/CT in patients affected with MM., Methods: Ten patients affected with MM underwent a standard 11C-Choline PET/CT and an 18F-FDG PET/CT within one week. The results of the two scans were compared in terms of number, sites and SUVmax of lesions., Results: Four patients (40%) had a negative concordant 11C-Choline and 18F-FDG PET/CT scans. Two patients (20%) had a positive 11C-Choline and 18F-FDG PET/CT scans that identified the same number and sites of bone lesions. The remaining four patients (40%) had a positive 11C-Choline and 18F-FDG PET/CT scan, but the two exams identified different number of lesions. Choline showed a mean SUVmax of 5 while FDG showed a mean SUVmax of 3.8 (P = 0.042). Overall, 11C-Choline PET/CT scans detected 37 bone lesions and 18F-FDG PET/CT scans detected 22 bone lesions but the difference was not significant (P = 0.8)., Conclusion: According to these preliminary data, 11C-Choline PET/CT appears to be more sensitive than 18F-FDG PET/CT for the detection of bony myelomatous lesions. If these data are confirmed in larger series of patients, 11C-Choline may be considered a more appropriate functional imaging in association with MRI for MM bone staging.

Purpose: To assess whether 18F-dopa PET/CT is able to provide information relevant in changing the clinical management of patients with gastro-enteropancreatic (GEP) tumours where there is negative or inconclusive conventional radiological imaging (ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI)) and 111In-pentetreotide scintigraphy., Materials and Methods: From January 2005 to October 2006, 84 patients with clinical and biochemical suspicion of GEP tumours were investigated by US and CT scans, MRI and 111In-pentetreotide scintigraphy. In 13/84 (15.4%) both conventional radiological imaging and 111In-pentetreotide scintigraphy provided negative or inconclusive findings, and patients were referred for 18F-dopa PET/CT imaging. Each patient received 5.3 MBq x kg(-1) 18F-dopa intravenously, and imaged 60 min later using a hybrid PET/CT scanner., Results: 18F-dopa PET/CT detected the primary tumour in all 13 patients (size range, 7-26 mm, mean, 18 mm; SUVmax range, 2.3-16.3, mean, 5.7) and further 12 unsuspected lesions (size range, 12-23 mm, mean 17; SUVmax range 2.8-12.7, mean 4.6). Confirmation of the PET/CT findings was obtained in all patients from histopathological analysis of tissue obtained after surgery and/or biopsy. All the 18F-dopa-positive primary lesions were confirmed as being the primary tumour at histology, whereas of the other 12 unsuspected 18F-dopa-positive lesions, 11 were found to be metastatic deposits and one due to unspecific inflammation (one false positive result). Notably, the results of 18F-dopa PET/CT imaging changed the clinical management in 11/13 patients (84%)., Conclusions: Our preliminary results suggest that 18F-dopa PET/CT has a promising role in GEP patients with negative or inconclusive findings at conventional radiological imaging and 111In-pentetreotide scintigraphy. The findings were helpful in biopsy guidance and played a major role in changing the management of those patients.

Purpose: The administration of new anticancer drugs in animal models is the first step from in vitro to in vivo pre-clinical protocols. At this stage it is crucial to ensure that cells are in the logarithmic phase of growth and to avoid vascular impairment, which can cause inhomogeneous distribution of the drug within the tumour and thus lead to bias in the final analysis of efficacy. In subcutaneous xenograft murine models, positivity for cancer is visually recognisable 2-3 weeks after inoculation, when a certain amount of necrosis is usually already present. The aim of this study was to evaluate the accuracy of FDG small animal PET for the early detection of malignant masses in a xenograft murine model of human rhabdomyosarcoma. A second goal was to analyse the metabolic behaviour of this xenograft tumour over time., Methods: We studied 23 nude mice, in which 7 x 10(6) rhabdomyosarcoma cells (RH-30 cell line) were injected in the dorsal subcutaneous tissues. Each animal underwent four FDG PET scans (GE, eXplore Vista DR) under gas anaesthesia. The animals were studied 2, 5, 14 and 20 days after inoculation. We administered 20 MBq of FDG via the tail vein. Uptake time was 60 min, and acquisition time, 20 min. Images were reconstructed with OSEM 2D iterative reconstruction and the target to background ratio (TBR) was calculated for each tumour. Normal subcutaneous tissue had a TBR of 0.3. Necrosis was diagnosed when one or more cold areas were present within the mass. All the animals were sacrificed and histology was available to verify PET results. PET results were concordant with the findings of necropsy and histology in all cases., Results: The incidence of the tumour was 69.6% (16/23 animals); seven animals did not develop a malignant mass. Ten of the 23 animals had a positive PET scan 2 days after inoculation. Nine of these ten animals developed a tumour; the remaining animal became negative, at the third scan. The positive predictive value of the early PET scan was 90% (9/10 animals) while the negative predictive value was 46% (6/13 animals). In the whole group of animals, mean TBR increased scan by scan. There was a statistically significant difference in TBR between 2 and 20 days after inoculation. Necrosis was present at the second scan in two animals, at the third scan in six animals and at the fourth scan in 11 animals., Conclusion: The high positive predictive value of FDG PET 2 days after inoculation means that an animal with a first positive scan has a very high likelihood of developing a mass and can be treated at an early stage with an experimental drug. Animals negative at this point in time will never develop a mass or will eventually do so at a late phase. As 2 of the 16 (12.5%) positive animals had necrosis at the second scan, indicating a vascular mismatch, it may be argued that animals should be treated 2 days after inoculation to guarantee homogeneous vascularisation (thereby ensuring a good drug supply within the tumour) in all subjects.

Purpose: Metastatic cancers of unknown primary origin are characterised by a poor prognosis, with a survival rate from diagnosis of approximately 12 months. Conventional radiological imaging allows detection of 20%-27% of primary cancers, whereas the detection rate with positron emission tomography (PET) is 24%-40%. The aim of this study was to assess the role of 18F-fluorodeoxyglucose (FDG) PET/computed tomography (CT) in the identification of occult primary cancers., Materials and Methods: The study population consisted of 38 consecutive patients with histologically proven metastatic disease and negative or nonconclusive conventional diagnostic procedures. All patients were studied by 18F-FDG PET performed according to the standard procedure (6 h of fasting, intravenous injection of 370 MBq 18F-FDG, and image acquisition with a PET/CT scanner for 4 min per bed position)., Results: 18F-FDG-PET/CT detected the occult primary cancer in 20 cases (53%), showing higher sensitivity than that reported for any other imaging modality, including PET., Conclusions: The encouraging results, if validated by larger series, support the use of PET/CT in patients with carcinoma of unknown primary origin and negative conventional imaging results.

This paper aims at discussing the utility of 18F-FDG PET/CT in the evaluation of paediatric solid extracranial tumours. Following a brief discussion of the basic principles and methodology of PET/CT system, it reviews the main characteristics of the tumours that can be visualised with 18F-FDG PET and presents examples of cases where the combined use of 18F-FDG PET/CT fusion imaging helped in the management of patients. It will also discuss the physiologic biodistribution of 18F-FDG, outlining the normal variants in the paediatric patients that may lead to misinterpretation.

To evaluate the sensitivity of 18-fluoro-2-deoxyglucose (18F-FDG) positron emission tomography (PET) in patients with mucosa-associated lymphoid tissue (MALT) lymphoma. A total of 32 patients with a histological diagnosis of extra-nodal MALT lymphoma were referred to the PET Centers in the last 2 years (2003 - 2004) and scanned with 18F-FDG-PET following standard procedures. Overall, the results of 50 18F-FDG-PET scans performed in either active disease state or in complete remission were reviewed. Sites of primary disease included stomach, lung, parotid, skin, orbit, mandible, esophagus and uterus. This study retrospectively enrolled 26 patients with known active disease. 18F-FDG-PET was true positive (TP) in 21/26 patients and false negative (FN) in 5/26. Sensitivity of 18F FDG-PET for extra-nodal MALT was 81%. The data show that 18FDG-PET is a useful diagnostic tool in order to stage, restage or monitor disease in patients with extra-nodal MALT lymphoma.

In recent years a number of studies have been published showing strong value of positron emission tomography using 18-Fluorine 2-fluoro-deoxy-D-glucose (FDG-PET) in term of diagnosis, response to treatment, disease recurrence and prognostic indicator in early restaging. This study observed 17 patients who presented contemporary disease progression in some localizations as well as regression in others (PROG + REG pattern); this investigation assessed that this unusual pattern of FDG uptake lead to an unfavorable prognosis. Among 1280 FDG-PET scans performed between August 2003 and December 2004 on patients affected by lymphoma with suspected recurrence, attention was focused on 17 patients presenting a PROG + REG pattern. At follow-up (4 months) only 1/17 (6%) patient was in complete remission after salvage therapy, while 6/17 (35%) had stable disease and 10/17 (59%) had rapid progression of the disease. This study further strengthens the role of FDG-PET in lymphoma patients follow-up, as it can provide useful information to better differentiate those cases who may benefit from conventional treatments from others in whom additional treatment would provide avoidable toxicity.

Unlabelled: This study evaluated the potential usefulness of (11)C-choline PET/CT for detection and localization of tumors within the prostate. We used the results of step-section histopathologic examination as the standard of reference., Methods: The results were analyzed on a sextant basis. We reviewed the results of the (11)C-choline PET/CT scans of 36 patients with prostate cancer and of 5 control subjects with bladder cancer. All patients underwent (11)C-choline PET/CT and, subsequently, radical prostatectomy with lymph node dissection within 1 mo. (11)C-Choline PET/CT scans were obtained 5-10 min after intravenous injection of 370-555 MBq of (11)C-choline. Images were reviewed visually and semiquantitatively using maximum SUV and tumor-to-background ratio., Results: On a sextant basis, histopathologic analysis detected cancer foci in 143 of 216 sextants; high-grade prostate intraepithelial neoplasm foci were detected in 89 of 216 sextants (in 59 sextants in association with carcinoma, in 30 sextants alone), acute prostatitis was detected in 7 of 216 sextants (in 3 sextants in association with carcinoma, in 4 sextants alone), and 39 of 216 sextants were normal. PET/CT demonstrated focal (11)C-choline uptake in 108 sextants (94 of which involved tumor), and 108 sextants showed no abnormal (11)C-choline uptake (49 of which were false negative). The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of PET/CT were 66%, 81%, 71%, 87%, and 55%, respectively. In the 5 control subjects, high-grade prostate intraepithelial neoplasm was detected at histologic examination in 16 of 30 sextants. PET/CT showed increased (11)C-choline uptake in 5 of 16 sextants., Conclusion: This study demonstrated the feasibility of using (11)C-choline PET/CT to identify cancer foci within the prostate. However, we also found that (11)C-choline PET/CT has a relative high rate of false-negative results on a sextant basis and that prostatic disorders other than cancer may accumulate (11)C-choline. Therefore, our data do not support the routine use of PET/CT with (11)C-choline as a first-line screening procedure for prostate cancer in men at high risk.

Background: Integrated positron emission tomography/computed tomography (PET/CT) systems represent a major development allowing functional and anatomical information to be acquired in a single examination session and therefore providing a more accurate definition of suspected lesion characteristics. Together with the increasing number of clinical settings in which PET/CT scans have been advocated, however, pitfalls in image interpretation have been reported., Methods: Four female subjects presenting a focal area of increased F-fluorodeoxyglucose (F-FDG) uptake with no evidence of a corresponding CT abnormality were included in the study. PET/CT scans were performed in all cases after the administration of 5.3 MBq . kg of F-FDG through a venous cannula., Results: Focal high uptake of F-FDG was observed in lung lesions without anatomical counterparts on CT in four female cases. The only common feature to all was the paravenous injection of the radiotracer., Conclusion: The lesions detected by PET may be related to distal lung microembolism originating from the site of paravenous injection.

Aim: The aim of the present study was to assess the accuracy of an hybrid PET/CT scanner in the evaluation of newly diagnosed parotid masses, comparing the results with those reported in the literature with using PET scanners only., Methods: The potential role of 18F-FDG PET/CT in distinguishing benign from malignant parotid masses in 14 consecutive patients was investigated. All patients were preoperatively evaluated by means of ultrasound (US), US-guided fine needle aspiration (FNA) cytology, computed tomography (CT) scan, magnetic resonance imaging (MRI) and 18F-FDG PET/CT. For To interpreting FDG PET findings, the right to left parotid (R/L) SUV max ratio was calculated in a group of 54 patients without evidence of parotideal disease (mean+/-SD = 1+/-0.2; range = 0.8-1.2); considering the R/L SUV max ratio, focal or diffuse uptakes <0.8 or >1.2 were considered as potentially pathological., Results: Imaging data were compared with surgical and histopathological findings. At FDG PET/CT, 9 false positive cases were found (8 Warthin's tumours, 1 pleomorphic adenoma), 1 false negative (acinar cell carcinoma), 4 true negative (1 Warthin's tumour, 1 pleomorphic adenoma, 1 lymph epithelial cyst, 1 parotid inflammation) whereas there was no case of true positive. The global accuracy of FGD PET/CT was rather low = at 29%., Conclusions: In agreement with other preliminary reports in which the FDG PET without CT fusion imaging was used, in our experience 18F-FDG PET/CT did not prove to play a significant role in differential diagnosis (benign vs malignant) of parotid masses. Further studies collecting larger groups of patients are needed to further elucidate this observation.

Objective: To evaluate the prevalence and scan interpretation criteria useful in identifying non-tumoural F-FDG focal uptakes (potential pitfalls) in patients who had been previously treated for a malignant lymphoma studied by positron emission tomography (PET)., Materials: Nine hundred and ninety-six consecutive PET scans obtained in 706 patients with malignant lymphoma were reviewed. All patients had been previously treated by first-line chemo-radiotherapy, plus surgery when required, and were then studied by FDG PET to investigate suspected recurrence at doubtful or inconclusive conventional radiological imaging (ultrasound, computed tomography, magnetic resonance imaging). PET was obtained with patients in the fasted condition and after i.v. injection of 370 MBq of F-FDG; imaging was acquired 60-90 min later. In patients with focal FDG uptake the final diagnosis was reached on the basis of histological findings or long-term follow-up., Results: Thirty-one of 134 PET scans (23.1%) showing focal FDG uptake were diagnosed as non-tumoural radiotracer uptake, related to the presence of brown fat in seven cases, thymic hyperplasia in five, muscles contraction in four, lymph node unspecific inflammation in four, mediastinal/pulmonary unspecific inflammation in four, gastritis in two, colitis in two, bacterial abscess in one, lactating breast in one, and herpes zoster in one. Each of the above cited situations has been reported in the literature, generally in the form of sporadic reports, as a potential cause of misinterpretation (false positive) in reading a PET scan with the potential for incorrect patient management. An accurate diagnosis in these patients was important for the following therapeutic decision making., Conclusions: In the whole series of patients with treated malignant lymphoma, the prevalence of non-tumoural FDG focal uptake during follow-up was relatively low (3.1%); conversely, it was relatively high when considering the sub-group of 'positive' PET only (23.1%). The importance of knowing these situations in order to avoid misinterpretation in reading PET scans needs to be emphasized. In this light, an accurate patient's history and a skilful nuclear medicine physician are very important factors. For the same purpose, it is reasonable to think that the use of hybrid PET/CT tomographs could also play an important role in helping to identify non-tumoural FDG focal uptake.

Purpose: The aim of this study was to evaluate the significance of increased uptake of 18F-fluorodeoxyglucose (FDG) in patients with malignant lymphoma (ML) studied by positron emission tomography (PET)., Methods: A total of 1,120 consecutive scans carried out in 848 patients were reviewed; all patients had a diagnosis of ML [574 non-Hodgkin's lymphoma (NHL) and 274 Hodgkin's disease (HD)] and were studied at completion of therapy, for suspected recurrence or during follow-up. PET was carried out after intravenous injection of 370 MBq of 18F-FDG; images were recorded after 60-90 min. Patients were selected whose reports indicated areas of increased FDG uptake. PET findings were considered positive for lymphomatous localisation when uptake occurred at sites of previous disease, in asymmetrical lymph nodes or in nodes unlikely to be affected by inflammation (mediastinal, except for hilar, and abdominal). PET findings were adjudged negative for neoplastic localisations in the following instances: physiological uptake (urinary, muscular, thymic or gastrointestinal in patients without MALT), symmetrical nodal uptake, uptake in lesions unrelated to lymphoma that had already been identified by other imaging methods at the time of PET scan, uptake at sites atypical for lymphoma, very low uptake and non-focal uptake. PET findings were compared with the results of other diagnostic procedures (including CT and ultrasound), biopsy findings and follow-up data., Results: Overall, 354 scans (in 256 patients) showed increased FDG uptake (244 scans in NHL and 110 in HD): in 286 cases, FDG uptake was considered pathological and indicative of ML, in 41 cases the findings were described as uncertain or equivocal and in 37 cases, FDG uptake was considered unrelated to ML (in ten scans, concurrent findings of abnormal FDG uptake attributed to ML and uptake assigned to other causes were obtained) . Of the 286 patients with positive PET findings, 274 (95.8%) were found to have residual or recurrent ML (i.e. true positives). Four of the 41 patients with inconclusive findings turned out to have ML, while in 13 patients, pathological processes other than ML could be identified as the cause of FDG uptake. ML was excluded in all patients with findings reported as non-pathological (100% true-negative rate). Therefore, the false-positive rate in our series was about 5%. The main cause of increased FDG uptake mimicking ML was inflammation., Conclusion: Our data confirm that 18F-FDG-PET has very high but not absolute specificity for ML. As already suggested, increased FDG uptake may also be observed in patients without active disease; in most cases, however, non-pathological FDG accumulation is properly identified. Less frequently, inconclusive scans are encountered; these cases are usually caused by inflammation, which subsequently resolves.

Purpose: Metastatic cancer of unknown primary origin is a syndrome characterised by a poor prognosis, with a typical survival rate from diagnosis of no longer than 1 year. Only 20-27% of primary tumours are identified by conventional radiological imaging. By contrast, it has been reported that 18F-fluorodeoxyglucose positron emission tomography (FDG PET) allows the identification of 24-40% of otherwise unrecognised primary tumours. To our knowledge, the studies on this topic have been conducted using 18F-FDG PET imaging alone. The aim of this study was to evaluate the potential additional diagnostic role of fused 18F-FDG PET-CT imaging for the detection of metastatic occult primary tumours., Methods: The study population consisted of 21 consecutive patients with biopsy-proven metastatic disease and negative conventional diagnostic procedures. Each patient underwent a PET scan, carried out according to a standard procedure (6 h of fasting, i.v. injection of 370 MBq of 18F-FDG and image acquisition with a dedicated PET-CT scanner for 4 min per bed position)., Results: 18F-FDG PET-CT detected the occult primary tumour in 12 patients (57% of cases), providing a detection rate higher than that reported with any other imaging modality, including conventional 18F-FDG PET., Conclusion: The favourable results of this study need to be confirmed in larger patient populations with long-term follow-up.

Background: Despite being a relatively rare disease, the incidence of malignant pleural mesothelioma (MPM) is expected to increase over the next two decades due to the long time interval elapsing between exposure to causative factors, mainly asbestos, and disease onset. Early disease stages have been reported to benefit from radical surgery. In more advanced disease stages, a multimodality treatment, including various combinations of chemotherapy, external radiotherapy and surgery, may provide some favourable results though the prognosis remains poor. In this regard, an accurate pre-treatment staging plays an important role in offering patients a more appropriate therapeutic planning. In some preliminary studies, (18)F-FDG PET has proven to be able to provide useful information for staging purpose, especially for the detection of metastatic spread to lymph nodes and distant sites., Material and Methods: In the present study, we investigated 15 consecutive patients with histologically proven MPM by means of conventional 2-mm thickness whole-body CT scan with and without contrast medium in comparison with wholebody (18)F-FDG PET/CT fusion imaging., Results: (18)F-FDG PET/CT did not provide additional information about the primary tumour (T) compared to CT scan, but identified a higher number of metastatic mediastinal lymph nodes (N) in 6 patients (40% of cases) and unknown metastatic disease to distant sites (M) in 3 patients (20% of cases). On the basis of PET/CT findings, treatment planning was changed in 5 patients (33.3% of cases)., Conclusions: Our data show that (18)F-FDG PET/CT fusion imaging can play a relevant role in the staging and treatment planning of MPM patients.

Malignant Pleural Mesothelioma (MPM) is a relatively rare neoplasia characterized by a poor prognosis. Recent studies show that new therapeutic approaches can lead to an improvement in life quality and to a prolonged survival; therefore, proper evaluation of MPM before, as well as after, therapy, is needed. The aim of this study was to evaluate the impact of 18F-FDG photon emission tomography (PET) scan compared to computed tomography (CT) findings in patients affected by MPM, whether untreated or already treated. We studied 15 consecutive patients (13 male and 2 female) with a histological diagnosis of MPM, with a mean age of 69.9 years (range: 38-78 years old) and a recent total-body CT scan. Five (5) patients were studied for staging, while 10 patients were studied after therapy. An FDG PET scan was carried out 60 minutes after an intravenous (i.v.) injection of 370 MBq of 18F-FDG. For each patient, we compared the PET stage to the CT stage, and evaluated the role of PET in choosing a therapeutic approach. In 9 of 15 (60%) patients, there was no difference between the PET and the CT stage. In 2 of 15 (13%) patients, PET upstaged the disease, while in 4 of 15 (27%) patients PET downstaged MPM. According to these results, patient management was changed in 3 cases. Specifically, 1 patient was excluded from surgery, and 2 patients had different chemotherapy. These data suggest that PET is useful in the evaluation of MPM, giving additional data that can clarify doubtful CT findings, especially regarding lymph node involvement and distant lesions. In conclusion, FDG PET was found to play a worth-while role in patient management.