Dosimetric Analysis of a Phase I Study of PSMA-Targeting Radiopharmaceutical Therapy With [ 177 Lu]Ludotadipep in Patients With Metastatic Castration-Resistant Prostate Cancer.

Objective: ¹⁷⁷ Lutetium [Lu] Ludotadipep is a novel prostate-specific membrane antigen targeting therapeutic agent with an albumin motif added to increase uptake in the tumors. We assessed the biodistribution and dosimetry of [ ¹⁷⁷ Lu]Ludotadipep in patients with metastatic castration-resistant prostate cancer (mCRPC).
Materials and Methods: Data from 25 patients (median age, 73 years; range, 60-90) with mCRPC from a phase I study with activity escalation design of single administration of [ ¹⁷⁷ Lu]Ludotadipep (1.85, 2.78, 3.70, 4.63, and 5.55 GBq) were assessed. Activity in the salivary glands, lungs, liver, kidneys, and spleen was estimated from whole-body scan and abdominal SPECT/CT images acquired at 2, 24, 48, 72, and 168 h after administration of [ ¹⁷⁷ Lu]Ludotadipep. Red marrow activity was calculated from blood samples obtained at 3, 10, 30, 60, and 180 min, and at 24, 48, and 72 h after administration. Organ- and tumor-based absorbed dose calculations were performed using IDAC-Dose 2.1.
Results: Absorbed dose coefficient (mean ± standard deviation) of normal organs was 1.17 ± 0.81 Gy/GBq for salivary glands, 0.05 ± 0.02 Gy/GBq for lungs, 0.14 ± 0.06 Gy/GBq for liver, 0.77 ± 0.28 Gy/GBq for kidneys, 0.12 ± 0.06 Gy/GBq for spleen, and 0.07 ± 0.02 Gy/GBq for red marrow. The absorbed dose coefficient of the tumors was 10.43 ± 7.77 Gy/GBq.
Conclusion: [ ¹⁷⁷ Lu]Ludotadipep is expected to be safe at the dose of 3.7 GBq times 6 cycles planned for a phase II clinical trial with kidneys and bone marrow being the critical organs, and shows a high tumor absorbed dose.
Competing Interests: Chansoo Park is an employee of FutureChem Co., Ltd., and Dae Yoon Chi is its chief executive officer. Seunggyun Ha has consultant agreement with FutureChem. Joo Hyun O has consultant agreements with FutureChem and Novartis, and as a member of the editorial board of the Korean Journal of Radiology, she was not involved in the editorial evaluation or decision to publish this article. All remaining authors have declared no conflicts of interest.
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