Selectivity of F-18-FLT and F-18-FDG for differentiating tumor from inflammation in a rodent model

Increased glucose metabolism of inflammatory tissues is the main source of false-positive F-18-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'-F-18-fluorothymidine (FLT) and F-18-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 F-18-FLT (n = 5) or F-18-FDG (n = 5). Pretreatment of the animals with thymidine phosphorylase (>1,000 U/kg, intravenously) before injection of F-18-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 F-18-FDG at 2 h after injection (13.2 +/- 3.0) were higher than those of F-18-FLT (3.8 +/- 1.3). F-18-FDG showed high physiologic uptake in brain and heart, whereas F-18-FLT was avidly taken up by bone marrow. F-18-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 F-18-FLT, for which this ratio was not significantly different from unity (1.3 +/- 0.4). Conclusion; In F-18-FDG PET images, both tumor and inflammation were visible, but F-18-FLT PET showed only the tumor. Thus, the hypothesis that F-18-FLT has a higher tumor specificity was confirmed in our animal model

Selectivity of F-18-FLT and F-18-FDG for differentiating tumor from inflammation in a rodent model

Increased glucose metabolism of inflammatory tissues is the main source of false-positive F-18-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'-F-18-fluorothymidine (FLT) and F-18-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 F-18-FLT (n = 5) or F-18-FDG (n = 5). Pretreatment of the animals with thymidine phosphorylase (>1,000 U/kg, intravenously) before injection of F-18-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 F-18-FDG at 2 h after injection (13.2 +/- 3.0) were higher than those of F-18-FLT (3.8 +/- 1.3). F-18-FDG showed high physiologic uptake in brain and heart, whereas F-18-FLT was avidly taken up by bone marrow. F-18-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 F-18-FLT, for which this ratio was not significantly different from unity (1.3 +/- 0.4). Conclusion; In F-18-FDG PET images, both tumor and inflammation were visible, but F-18-FLT PET showed only the tumor. Thus, the hypothesis that F-18-FLT has a higher tumor specificity was confirmed in our animal model

Improved GMP-compliant multi-dose production and quality control of 6-[18F]fluoro-L-DOPA

Background: 6-[18F]Fluoro-L-3,4-dihydroxyphenylalanine (FDOPA) is a frequently used radiopharmaceutical for detecting neuroendocrine and brain tumors and for the differential diagnosis of Parkinson’s disease. To meet the demand for FDOPA, a high-yield GMP-compliant production method is required. Therefore, this study aimed to improve the FDOPA production and quality control procedures to enable distribution of the radiopharmaceutical over distances. FDOPA was prepared by electrophilic fluorination of the trimethylstannyl precursor with [18F]F2, produced from [18O]2 via the double-shoot approach, leading to FDOPA with higher specific activity as compared to FDOPA which was synthesized, using [18F]F2 produced from 20Ne, leading to FDOPA with a lower specific activity. The quality control of the product was performed using a validated UPLC system and compared with quality control with a conventional HPLC system. Impurities were identified using UPLC-MS. Results: The [18O]2 double-shoot radionuclide production method yielded significantly more [18F]F2 with less carrier F2 than the conventional method starting from 20Ne. After adjustment of radiolabeling parameters substantially higher amounts of FDOPA with higher specific activity could be obtained. Quality control by UPLC was much faster and detected more side-products than HPLC. UPLC-MS showed that the most important side-product was FDOPA-quinone, rather than 6-hydroxydopa as suggested by the European Pharmacopoeia. Conclusion: The production and quality control of FDOPA were significantly improved by introducing the [18O]2 double-shoot radionuclide production method, and product analysis by UPLC, respectively. As a result, FDOPA is now routinely available for clinical practice and for distribution over distances