Comparison of sigma-ligands and metabolic PET tracers for differentiating tumor from inflammation

Novel radiopharmaceuticals for the detection of tumors and their metastases may be of clinical interest if they are more tumor selective than (18)F-FDG. Increased glucose metabolism of inflammatory tissues is the main source of false-positive (18)F-FDG PET findings in oncology.

We compared the biodistribution of 4 PET tracers (2 sigma-receptor ligands, (11)C-choline, and (11)C-methionine) with previously published biodistribution data of 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) and of (18)F-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 (18)F and 74 MBq for (11)C).

(18)F-FDG showed the highest tumor-to-muscle ratio of all radiopharmaceuticals (13.2 +/- 3.0, mean +/- SD), followed at a large distance by the sigma-1 ligand (11)C-SA4503 (5.1 +/- 1.7), (18)F-FLT (3.8 +/- 1.3), the non-subtype-selective sigma-ligand (18)F-FE-SA5845 (3.3 +/- 1.5), (11)C-choline (3.1 +/- 0.4), and (11)C-methionine (2.8 +/- 0.3). sigma-Ligands and (18)F-FLT were relatively tumor selective ((18)F-FE-SA5845, greater than 30-fold; (11)C-SA4503 and (18)F-FLT, greater than 10-fold). The tumor selectivity of (11)C-methionine was only slightly better than that of (18)F-FDG. (11)C-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.

sigma-Ligands and (18)F-FLT were more tumor selective than (18)F-FDG, (11)C-choline, or (11)C-methionine in our animal model. However, these novel radiopharmaceuticals were less sensitive than were the established oncologic tracers.