Comparison of somatostatin receptor agonist and antagonist for peptide receptor radionuclide therapy: A pilot study

Preclinical and clinical studies have indicated that somatostatin receptor (sst)-expressing tumors demonstrate higher uptake of radiolabeled sst antagonists than of sst agonists. In 4 consecutive patients with advanced neuroendocrine tumors, we evaluated whether treatment with ¹⁷⁷Lu- labeled sst antagonists is feasible. Methods: After injection of approximately 1 GBq of ¹⁷⁷Lu-DOTA-[Cpa-c(DCys-Aph(Hor)-DAph(Cbm)-Lys-Thr-Cys)-DTyr- NH₂] (¹⁷⁷Lu-DOTA-JR11) and ¹⁷⁷Lu-DOTATATE, 3-dimensional voxel dosimetry analysis based on SPECT/CT was performed. A higher tumor-to-organ dose ratio for ¹⁷⁷Lu-DOTAJR11 than for ¹⁷⁷Lu-DOTATATE was the prerequisite for treatment with ¹⁷⁷Lu-DOTA-JR11. Results: Reversible minor adverse effects of ¹⁷⁷Lu-DOTA-JR11 were observed. ¹⁷⁷Lu-DOTA-JR11 showed a 1.7-10.6 times higher tumor dose than ¹⁷⁷Lu-DOTATATE. At the same time, the tumor-to-kidney and tumor-to-bone marrow dose ratio was 1.1-7.2 times higher. All 4 patients were treated with ¹⁷⁷Lu-DOTA-JR11, resulting in partial remission in 2 patients, stable disease in 1 patient, and mixed response in the other patient. Conclusion: Treatment of neuroendocrine tumors with radiolabeled sst antagonists is clinically feasible and may have a significant impact on peptide receptor radionuclide therapy. COPYRIGHT