Preclinical Evaluation of a High-Affinity 18F-Trifluoroborate Octreotate Derivative for Somatostatin Receptor Imaging

Recent studies have highlighted the high sensitivity of PET imaging with Ga-68-labeled octreotide derivatives for the detection and staging of neuroendocrine tumors. A somatostatin receptor ligand that is easily radiolabeled with F-18-fluoride could improve the availability of PET imaging of neuroendocrine tumors. We report an alkyltrifluoroborate-octreotate conjugate that is radiolabeled in a 1-step F-18 exchange reaction in high yield and with high specific activity. Methods: We conjugated a new alkyltrifluoroborate to octreotate to obtain AMBF(3)-TATE, which. was stored in 50-nmol aliquots for radiolabeling. F-18 labeling was performed by F-18-F-19 isotope exchange with F-18-fluoride, and the tracer was purified by C18 cartridge separation. The radiochemical yield was 20%-25%. PET imaging and biodistribution were performed on mice bearing AR42J tumor xenografts. Results: AMBF(3)-TATE bound the somatostatin receptor subtype 2 with high affinity (inhibition constant, 0.13 +/- 0.03 nM). Starting with 29.6-37 GBq (0.8-1 Ci) of F-18-fluoride, more than 7.4 GBq (>200 mCi) of F-18-AMBF(3)-TATE were obtained in 25 min (n = 5) with greater than 99% radiochemical purity at high specific activity (>111 GBq [3 Ci]/mu mol). F-18-AMBF3-TATE was stable in plasma. PET imaging and biodistribution showed rapid renal excretion with low liver activity. High tumor uptake (10.11% +/- 1.67% injected dose/g, n = 5) was detected at 60 min after injection. Bone uptake was negligible. Tumor-to-liver, tumor-to-blood, tumor-to-muscle, and tumor-to-bone ratios (at 60 min) were 26.2 +/- 0.8, 25.1 +/- 1.0, 89.0 +/- 3.1, and 21.3 +/- 3.6, respectively. Conclusion: F-18-AMBF(3)-TATE was radiolabeled in high yield and at high specific activity, did not require high-performance liquid chromatography purification, exhibited unexpectedly high binding affinity to somatostatin receptor subtype 2, and showed excellent pharmacokinetic properties in vivo, with high tumor uptake and high contrast ratios.