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Comparison of Sigma-Ligands and Metabolic PET Tracers for Differentiating Tumor from Inflammation

¹ Department of Nuclear Medicine and Molecular Imaging, University Medical Center of Groningen, University of Groningen, The Netherlands; and ² Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan

Correspondence: For correspondence or reprints contact: Aren van Waarde, PhD, Department of Nuclear Medicine and Molecular Imaging, University Medical Center of Groningen, P.O. Box 30001, 9700RB Groningen, The Netherlands. E-mail: a.van.waarde{at}pet.umcg.nl

Novel radiopharmaceuticals for the detection of tumors and their metastases may be of clinical interest if they are more tumor selective than ¹⁸F-FDG. Increased glucose metabolism of inflammatory tissues is the main source of false-positive ¹⁸F-FDG PET findings in oncology. Methods: We compared the biodistribution of 4 PET tracers (2 -receptor ligands, ¹¹C-choline, and ¹¹C-methionine) with previously published biodistribution data of 3'-deoxy-3'-¹⁸F-fluorothymidine (¹⁸F-FLT) and of ¹⁸F-FDG in the same animal model. The model consisted of male 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 of PET tracer (approximately 30 MBq in the case of ¹⁸F and 74 MBq for ¹¹C). Results: ¹⁸F-FDG showed the highest tumor-to-muscle ratio of all radiopharmaceuticals (13.2 ± 3.0, mean ± SD), followed at a large distance by the -1 ligand ¹¹C-SA4503 (5.1 ± 1.7), ¹⁸F-FLT (3.8 ± 1.3), the non–subtype-selective -ligand ¹⁸F-FE-SA5845 (3.3 ± 1.5), ¹¹C-choline (3.1 ± 0.4), and ¹¹C-methionine (2.8 ± 0.3). -Ligands and ¹⁸F-FLT were relatively tumor selective (¹⁸F-FE-SA5845, greater than 30-fold; ¹¹C-SA4503 and ¹⁸F-FLT, greater than 10-fold). The tumor selectivity of ¹¹C-methionine was only slightly better than that of ¹⁸F-FDG. ¹¹C-Choline showed equal uptake in tumor and inflammation. All tracers were avidly taken up by proliferative tissue (small intestine, bone marrow). High physiologic uptake of some compounds was observed in brain, heart, lung, pancreas, spleen, and salivary gland. Conclusion: -Ligands and ¹⁸F-FLT were more tumor selective than ¹⁸F-FDG, ¹¹C-choline, or ¹¹C-methionine in our animal model. However, these novel radiopharmaceuticals were less sensitive than were the established oncologic tracers.

Key Words: tumor • sigma-ligands • inflammation • choline • methionine

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