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

Journal of Nuclear Medicine

Maral Pourghiasian¹  François Bénard¹  Jinhe Pan¹  Zhibo Liu¹  David M. Perrin¹  Kuo-Shyan Lin¹ 

关键词: positron emission tomography;    somatostatin receptor;    octreotide;    octreotate;    ¹⁸F-BF₃;    1-step ¹⁸F-labeling;   

DOI  :  10.2967/jnumed.114.137836

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

Recent studies have highlighted the high sensitivity of PET imaging with 68Ga-labeled octreotide derivatives for the detection and staging of neuroendocrine tumors. A somatostatin receptor ligand that is easily radiolabeled with 18F-fluoride could improve the availability of PET imaging of neuroendocrine tumors. We report an alkyltrifluoroborate–octreotate conjugate that is radiolabeled in a 1-step 18F exchange reaction in high yield and with high specific activity. Methods: We conjugated a new alkyltrifluoroborate to octreotate to obtain AMBF3-TATE, which was stored in 50-nmol aliquots for radiolabeling. 18F labeling was performed by 18F-19F isotope exchange with 18F-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: AMBF3-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 18F-fluoride, more than 7.4 GBq (>200 mCi) of 18F-AMBF3-TATE were obtained in 25 min (n = 5) with greater than 99% radiochemical purity at high specific activity (>111 GBq [3 Ci]/μmol). 18F-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: 18F-AMBF3-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.

【 授权许可】

Unknown