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Purpose: S-[11C]-methyl-L-cysteine ([11C]MCYS) has been claimed to offer higher tumor selectivity than L-[methyl- 11C]methionine ([11C]MET). We examined this claim in animal models.Procedures: Rats with implanted untreated (n = 10) or irradiated (n = 7, 1 × 25 Gy, on day 8) orthotopic gliomas were scanned after 6, 9, and 12 days, using positron emission tomography. Rats with striatal injections of saline (n = 9) or bacterial lipopolysaccharide (n = 9) were scanned after 3 days.Results: Uptake of the two tracers in untreated gliomas was similar. [11C]MCYS was not accumulated in salivary glands, nasal epithelium, and healing wounds, in contrast to [11C]MET, but showed 40 % higher accumulation in the healthy brain. Both tracers showed a reduced tumor uptake 4 days after irradiation and minor accumulation in inflamed striatum. [11C]MCYS indicated higher lesion volumes than [11C]MET (untreated tumor + 47 %; irradiated tumor up to + 500 %; LPS-inflamed striatum + 240 %).Conclusions: [11C]MCYS was less accumulated in some non-tumor tissues than [11C]MET, but showed lower tumor-to-brain contrast. [ABSTRACT FROM AUTHOR]

Objectives: Positron emission tomography (PET) scanning may provide information on changes in the density and affinity of airway beta-adrenoceptors in lung diseases. However, the injection of a radiolabeled beta-blocker results in a pulmonary PET signal that reflects the binding of the ligand in the alveoli and not in the airways. Better discrimination between alveolar and airway beta-adrenoceptors may be possible with an inhaled radioligand. Design: A nebulizer was used to administer the antagonist S-11C-CGP12388 in aerosol form. Eight volunteers inhaled the tracer twice, at baseline and after pretreatment with a beta-adrenergic drug. In both PET scan studies, a dynamic scan of the lungs was followed by a whole-body scan to assess the inhaled dose. Pulmonary uptake was quantified using a region-of-interest-based analysis. Setting: University hospital. Participants: Healthy volunteers. Interventions: Pretreatment consisted either of inhaled salbutamol (400 microg, 20 min before the scan), or orally administered pindolol (3 x 5 mg during a period of 16 h before PET scanning). Results: Drug pretreatment did not affect pulmonary deposition of the radioligand. The agonist salbutamol accelerated the monoexponential washout of 11C not only in the peripheral lung (mainly alveoli), but also in the central lung (mainly airways) and in the main bronchi. An even larger increase of the washout rate was induced by the antagonist pindolol. Conclusion: The similar effects of pindolol and salbutamol on tracer kinetics suggest that accelerated washout is due to the blockade of beta-adrenoceptors. Thus, the interaction of drugs with airway beta-adrenoceptors can be visualized using PET scanning and an inhaled radioligand. [ABSTRACT FROM AUTHOR]

Unlabelled: The objective of this study was to compare 18F-3'-fluoro-3'-deoxy-L-thymidine (FLT) PET with clinical TNM staging, including that by 18F-FDG PET, in patients with non-small cell lung cancer (NSCLC)., Methods: Patients with NSCLC underwent whole-body 18F-FDG PET and whole-body 18F-FLT PET, using a median of 360 MBq of 18F-FDG (range, 160-500 MBq) and a median of 210 MBq of 18F-FLT (range, 130-420 MBq). 18F-FDG PET was performed 90 min after 18F-FDG injection, and 18F-FLT PET was performed 60 min after 18F-FLT injection. Two viewers independently categorized the localization and intensity of tracer uptake for all lesions. All 18F-FDG PET and 18F-FLT PET lesions were compared. Staging with 18F-FLT PET was compared with clinical TNM staging based on the findings of history, physical examination, bronchoscopy, CT, and 18F-FDG PET. From 8 patients, standardized uptake values (SUVs) were calculated. Maximal SUV and mean SUV were calculated., Results: Sixteen patients with stage IB-IV NSCLC and 1 patient with strong suspicion of NSCLC were investigated. Sensitivity on a lesion-by-lesion basis was 80% for the 8 patients who received treatment before 18F-FLT PET and 27% for the 9 patients who did not receive pretreatment, using 18F-FDG PET as the reference standard. Compared with clinical TNM staging, staging by 18F-FLT PET was correct for 8 of 17 patients: 5 of 9 patients in the group with previous therapy and 3 of 8 patients in the group without previous therapy. The maximal SUV of 18F-FLT PET, at a median of 2.7 and range of 0.8-4.5, was significantly lower than that of 18F-FDG PET, which had a median of 8.0 and range of 3.7-18.8 (n = 8; P = 0.012). The mean SUV of 18F-FLT PET, at a median of 2.7 and range of 1.4-3.3, was significantly lower than that of 18F-FDG PET, which had a median of 6.2 and range of 2.8-13.9 (n = 6; P = 0.027)., Conclusion: 18F-FLT PET is not useful for staging and restaging NSCLC.

Unlabelled: Increased glucose metabolism of inflammatory tissues is the main source of false-positive (18)F-FDG PET findings in oncology. It has been suggested that radiolabeled nucleosides might be more tumor specific., Methods: To test this hypothesis, we compared the biodistribution of 3'-deoxy-3'-(18)F-fluorothymidine (FLT) and (18)F-FDG in Wistar rats that bore tumors (C6 rat glioma in the right shoulder) and also had sterile inflammation in the left calf muscle (induced by injection of 0.1 mL of turpentine). Twenty-four hours after turpentine injection, the rats received an intravenous bolus (30 MBq) of either (18)F-FLT (n = 5) or (18)F-FDG (n = 5). Pretreatment of the animals with thymidine phosphorylase (>1,000 U/kg, intravenously) before injection of (18)F-FLT proved to be necessary to reduce the serum levels of endogenous thymidine and achieve satisfactory tumor uptake of radioactivity., Results: Tumor-to-muscle ratios of (18)F-FDG at 2 h after injection (13.2 +/- 3.0) were higher than those of (18)F-FLT (3.8 +/- 1.3). (18)F-FDG showed high physiologic uptake in brain and heart, whereas (18)F-FLT was avidly taken up by bone marrow. (18)F-FDG accumulated in the inflamed muscle, with 4.8 +/- 1.2 times higher uptake in the affected thigh than in the contralateral healthy thigh, in contrast to (18)F-FLT, for which this ratio was not significantly different from unity (1.3 +/- 0.4)., Conclusion: In (18)F-FDG PET images, both tumor and inflammation were visible, but (18)F-FLT PET showed only the tumor. Thus, the hypothesis that (18)F-FLT has a higher tumor specificity was confirmed in our animal model.

Unlabelled: The feasibility of (18)F-3'-fluoro-3'-deoxy-L-thymidine PET (FLT PET) for detecting laryngeal cancer was investigated and compared with (18)F-FDG PET., Methods: Eleven patients diagnosed with or strongly suspected of having recurrent laryngeal cancer and 10 patients with histologically proven primary laryngeal cancer underwent attenuation-corrected (18)F-FLT PET imaging 60 min after injection of a median of 213 MBq (range, 175-400 MBq) (18)F-FLT and attenuation-corrected (18)F-FDG PET imaging 90 min after injection of a median of 340 MBq (range, 165-650 MBq) (18)F-FDG. All patients were staged by endoscopy and CT according to the Union Internationale Contre la Cancer TNM staging system. All patients underwent biopsy of the laryngeal area after imaging. Lesions seen on (18)F-FDG PET and (18)F-FLT PET were compared with histopathologic results. Mean SUVs, maximum SUVs, and tumor-to-nontumor (TNT) ratios were calculated for (18)F-FLT and (18)F-FDG. Wilcoxon nonparametric testing was used for comparison of (18)F-FDG with (18)F-FLT uptake. The Spearman correlation coefficient was used to correlate mean SUVs, maximum SUVs, and TNT ratios of (18)F-FDG PET and (18)F-FLT PET. Two-tailed P values < 0.05 were considered significant., Results: (18)F-FDG PET and (18)F-FLT PET detected laryngeal cancer correctly in 15 of 17 patients. One lesion judged as positive on (18)F-FDG PET turned out to be normal tissue. Of 2 lesions judged as positive on (18)F-FLT PET, 1 turned out to be inflammation and the other to be normal tissue. Maximum SUVs were 3.3 (range, 1.9-8.5) for (18)F-FDG and 1.6 (range, 1.0-5.7) for (18)F-FLT (P < 0.001). Mean SUVs were 2.7 (range, 1.5-6.5) for (18)F-FDG and 1.2 (range, 0.8-3.8) for (18)F-FLT (P < 0.001). TNT was 1.9 (range, 1.3-4.7) for (18)F-FDG and 1.5 (range, 1.1-3.5) for (18)F-FLT (P < 0.05)., Conclusion: The numbers of laryngeal cancers detected with (18)F-FLT PET and (18)F-FDG PET were equal. In laryngeal cancer, the uptake of (18)F-FDG is higher than that of (18)F-FLT.

Unlabelled: In this study, the feasibility of 3'-(18)F-fluoro-3'-deoxy-L-thymidine PET ((18)F-FLT PET) for staging patients with clinical stage III melanoma was investigated., Methods: Ten patients with melanoma and metastases to the locoregional draining lymph nodes, clinical stage III-based on physical examination, chest radiography, lactate dehydrogenase, and histopathologic confirmation-underwent a whole-body (18)F-FLT PET scan 1 h after injection of a median 400-MBq dose (range, 185-430 MBq) of (18)F-FLT. All (18)F-FLT PET lesions were verified using the American Joint Committee on Cancer Staging System, which includes physical examination, spiral CT, ultrasound, chest radiography, and histopathologic examinations. Size and mitotic rate of metastatic lymph nodes and skin metastases were determined., Results: All histopathologic samples and (18)F-FLT PET lesions were categorized over anatomic regions and correlated. All locoregional metastases were correctly visualized by (18)F-FLT PET. Region-based sensitivity for detection of lymph node metastatic disease was 88%. There were 3 true-negative and 2 false-positive lesions. The detection limit for lymph node metastases appeared to be approximately 6 mm or a mitotic rate of 9 mitoses per 2 mm(2). Two patients were upstaged by (18)F-FLT PET, which was confirmed by CT. In 3 patients, (18)F-FLT PET detected a total of 3 additional lesions with therapeutic consequences, without influencing staging. These lesions were initially missed by clinical staging., Conclusion: (18)F-FLT PET seems promising for (re)staging purposes in clinical stage III melanoma. Further research is needed, in which (18)F-FLT PET should be compared with (18)F-FDG PET.