Message: file_get_contents(https://...@gmail.com&api_key=61f08fa0b96a73de8c900d749fcb997acc09): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
Comparison of novel PSMA-targeting [Lu]Lu-P17-087 with its albumin binding derivative [Lu]Lu-P17-088 in metastatic castration-resistant prostate cancer patients: a first-in-human study. | LitMetric
Department of Nuclear Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing St., Dongcheng District, Beijing, 100730, China.
Published: July 2024
AI Article Synopsis
Article Abstract
Purpose: Prostate-specific membrane antigen (PSMA) is a promising target for diagnosis and radioligand therapy (RLT) of prostate cancer. Two novel PSMA-targeting radionuclide therapy agents, [Lu]Lu-P17-087, and its albumin binder modified derivative, [Lu]Lu-P17-088, were evaluated in metastatic castration-resistant prostate cancer (mCRPC) patients. The primary endpoint was dosimetry evaluation, the second endpoint was radiation toxicity assessment (CTCAE 5.0) and PSA response (PCWG3).
Methods: Patients with PSMA-positive tumors were enrolled after [Ga]Ga-PSMA-11 PET/CT scan. Five mCRPC patients received [Lu]Lu-P17-087 and four other patients received [Lu]Lu-P17-088 (1.2 GBq/patient). Multiple whole body planar scintigraphy was performed at 1.5, 4, 24, 48, 72, 120 and 168 h after injection and one SPECT/CT imaging was performed at 24 h post-injection for each patient. Dosimetry evaluation was compared in both patient groups.
Results: Patients showed no major clinical side-effects under this low dose treatment. As expected [Lu]Lu-P17-088 with longer blood circulation (due to its albumin binding) exhibited higher effective doses than [Lu]Lu-P17-087 (0.151 ± 0.036 vs. 0.056 ± 0.019 mGy/MBq, P = 0.001). Similarly, red marrow received 0.119 ± 0.068 and 0.048 ± 0.020 mGy/MBq, while kidney doses were 0.119 ± 0.068 and 0.046 ± 0.022 mGy/MBq, respectively. [Lu]Lu-P17-087 demonstrated excellent tumor uptake and faster kinetics; while [Lu]Lu-P17-088 displayed a slower washout and higher average dose (7.75 ± 4.18 vs. 4.72 ± 2.29 mGy/MBq, P = 0.018). After administration of [Lu]Lu-P17-087 and [Lu]Lu-P17-088, 3/5 and 3/4 patients showed reducing PSA values, respectively.
Conclusion: [Lu]Lu-P17-088 and [Lu]Lu-P17-087 displayed different pharmacokinetics but excellent PSMA-targeting dose delivery in mCRPC patients. These two agents are promising RLT agents for personalized treatment of mCRPC. Further studies with increased dose and frequency of RLT are warranted to evaluate the potential therapeutic efficacy.
Trial Registration: Lu-P17-087/Lu-P17-088 in Patients with Metastatic Castration-resistant Prostate Cancer (NCT05603559, Registered at 25 October, 2022). URL OF REGISTRY: https://classic.
