Multi-Cycle Dosimetry of the Albumin-Binding Prostate-Specific Membrane Antigen Ligand [¹⁷⁷Lu]Ludotadipep in Metastatic Androgen Pathway Modulator-Resistant Prostate Cancer with Adjusted Red Marrow Modeling.
4 affiliations
- 1Department of Radiology, Division of Nuclear Medicine, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
- 2Research Institute of Labeling, FutureChem Co. Ltd., Seoul 06591, Republic of Korea.
- 3Department of Urology, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
- 4Department of Internal Medicine, Division of Medical Oncology, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
Abstract
Purpose: This dosimetry study aimed to evaluate the organ-absorbed doses and safety profile of multiple doses of [¹⁷⁷Lu]Ludotadipep, a novel PSMA-targeted radiopharmaceutical with an albumin-binding motif, in patients with metastatic androgen pathway modulator-resistant (mAPMR) prostate cancer. Methods: Twenty patients received a total of 68 cycles of [¹⁷⁷Lu]Ludotadipep (3.70 GBq/cycle, up to six cycles, 8-week intervals), and dosimetry analysis was done for 67 cycles. Organ-absorbed doses were estimated using planar and SPECT/CT imaging and blood-based methods. Red marrow dose was calculated using a red marrow-to-blood activity concentration ratio (RMBLR) derived from a hematocrit-adjusted model for large molecules and cross-checked by comparison with data derived from quantitative SPECT/CT images and blood samples. Results: The hematocrit-adjusted RMBLR of 0.28 was consistent with physiologic expectations for albumin-bound agents for marrow dosimetry. The highest absorbed dose coefficients in the first cycle were in the salivary glands and kidneys (1.22 ± 0.530 and 0.674 ± 0.330 Gy/GBq, respectively), while the red marrow dose (0.0533 ± 0.0115 Gy/GBq) was lower. Summing the cycle-specific mean absorbed dose coefficients and multiplying by 3.70 GBq per cycle yielded projected six-cycle absorbed doses of 18.1 Gy for kidneys, 15.3 Gy for salivary glands, and 1.28 Gy for red marrow, all of which were below the reference dose constraints. Salivary gland dose coefficients declined significantly over repeated cycles (p < 0.001), possibly from radiation-induced tissue damage. Conclusion: [¹⁷⁷Lu]Ludotadipep demonstrates a favorable dosimetric safety profile across multiple cycles, up to six cycles. Application of an appropriately adjusted RMBLR for albumin-binding behavior allowed for reproducible red marrow dose estimation.
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BibTeX
@article{ha2026multicycle,
title = {{Multi-Cycle Dosimetry of the Albumin-Binding Prostate-Specific Membrane Antigen Ligand [¹⁷⁷Lu]Ludotadipep in Metastatic Androgen Pathway Modulator-Resistant Prostate Cancer with Adjusted Red Marrow Modeling.}},
author = {Seunggyun Ha and Joo Hyun O and Chansoo Park and Sun Ha Boo and Dongho Shin and Hyong Woo Moon and Ie Ryung Yoo and In-Ho Kim and Ji Youl Lee},
journal = {Pharmaceutics},
year = {2026},
month = oct,
doi = {10.3390/pharmaceutics18101328},
url = {https://europepmc.org/article/MED/42942858},
note = {CC BY},
}
RIS
TY - JOUR
TI - Multi-Cycle Dosimetry of the Albumin-Binding Prostate-Specific Membrane Antigen Ligand [¹⁷⁷Lu]Ludotadipep in Metastatic Androgen Pathway Modulator-Resistant Prostate Cancer with Adjusted Red Marrow Modeling.
AU - Seunggyun Ha
AU - Joo Hyun O
AU - Chansoo Park
AU - Sun Ha Boo
AU - Dongho Shin
AU - Hyong Woo Moon
AU - Ie Ryung Yoo
AU - In-Ho Kim
AU - Ji Youl Lee
PY - 2026
DA - 2026/10/20
JO - Pharmaceutics
DO - 10.3390/pharmaceutics18101328
UR - https://europepmc.org/article/MED/42942858
AB - Purpose: This dosimetry study aimed to evaluate the organ-absorbed doses and safety profile of multiple doses of [¹⁷⁷Lu]Ludotadipep, a novel PSMA-targeted radiopharmaceutical with an albumin-binding motif, in patients with metastatic androgen pathway modulator-resistant (mAPMR) prostate cancer. Methods: Twenty patients received a total of 68 cycles of [¹⁷⁷Lu]Ludotadipep (3.70 GBq/cycle, up to six cycles, 8-week intervals), and dosimetry analysis was done for 67 cycles. Organ-absorbed doses were estimated using planar and SPECT/CT imaging and blood-based methods. Red marrow dose was calculated using a red marrow-to-blood activity concentration ratio (RMBLR) derived from a hematocrit-adjusted model for large molecules and cross-checked by comparison with data derived from quantitative SPECT/CT images and blood samples. Results: The hematocrit-adjusted RMBLR of 0.28 was consistent with physiologic expectations for albumin-bound agents for marrow dosimetry. The highest absorbed dose coefficients in the first cycle were in the salivary glands and kidneys (1.22 ± 0.530 and 0.674 ± 0.330 Gy/GBq, respectively), while the red marrow dose (0.0533 ± 0.0115 Gy/GBq) was lower. Summing the cycle-specific mean absorbed dose coefficients and multiplying by 3.70 GBq per cycle yielded projected six-cycle absorbed doses of 18.1 Gy for kidneys, 15.3 Gy for salivary glands, and 1.28 Gy for red marrow, all of which were below the reference dose constraints. Salivary gland dose coefficients declined significantly over repeated cycles (p < 0.001), possibly from radiation-induced tissue damage. Conclusion: [¹⁷⁷Lu]Ludotadipep demonstrates a favorable dosimetric safety profile across multiple cycles, up to six cycles. Application of an appropriately adjusted RMBLR for albumin-binding behavior allowed for reproducible red marrow dose estimation.
SN - 1999-4923
ER -