ORIGINAL RESEARCH article
Front. Oncol.
Sec. Radiation Oncology
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1600821
A Proof-of-Concept Study of Personalized Dosimetry for Targeted Radioligand Therapyusing Pre-treatment Diagnostic Dynamic PET/CT and Monte Carlo Simulation
Provisionally accepted- 1Western University, London, Canada
- 2Carleton University, Ottawa, Ontario, Canada
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Theranostics combines diagnostic imaging (e.g., ¹⁸F-PSMA PET) with targeted radioligand therapy (TRT; e.g., ¹⁷⁷Lu-PSMA-617), but personalized dosimetry remains challenging due to complex dose calculations and the impractical need for multi-day post-treatment SPECT/CT imaging. We propose a proof-of-concept framework that uses pre-treatment PET/CT and Monte Carlo modeling to predict patient-specific TRT doses, eliminating the need for serial post-treatment imaging. Dynamic 18F-DCFPyL PET/CT scans (22 min) were obtained from six prostate cancer patients. Tissue time-integrated activity (TIA)—the total decays from accumulated radioligand—was estimated as the product of an extrapolated arterial time-activity curve (TAC) area and the Logan distribution volume (LDV) derived from graphical analysis. Voxel-wise LDV showed excellent linearity (mean R² = 0.99997 ± 0.00005). We generated patient-specific 177Lu-PSMA-617 TIA maps and, along with CT-derived tissue geometry, used the egs_mird Monte Carlo engine to compute absorbed dose in prostate tumors, normal prostate tissue, and bone marrow. Biological effective dose (BED) was estimated using an extended linear quadratic model accounting for dose rate, DNA repair, and repopulation effects. Substantial interpatient dose variability was observed using a uniform radioligand dose: 10.4 ± 4.9 Gy/GBq in tumors, 5.1 ± 0.7 Gy/GBq in normal prostate, and 1.0 ± 0.3 Gy/GBq in bone marrow. These differences were driven by variability in LDV (radioligand binding) and arterial TACs (influenced by tumor burden and clearance). Our framework enables pre-treatment, voxel-based TRT dose estimation using diagnostic PET/CT alone. This method addresses patient-specific differences in pharmacokinetics and biodistribution that impact therapeutic response and toxicity—critical for optimizing TRT and combining it with external beam radiation therapy (EBRT) or brachytherapy when appropriate. This LDV-based pre-treatment dosimetry approach represents a step toward precision radiotheranostics by allowing dose personalization without the logistical burden of post-treatment SPECT/CT. While promising, this method requires further validation in larger cohorts and comparison with post-treatment dosimetry to confirm its clinical utility
Keywords: Targeted Radioligand Therapy (TRT), Personalized dosimetry, Monte Carlo simulation, tracer kinetics, 177Lu-PSMA-617, Biological effective dose (BED)
Received: 27 Mar 2025; Accepted: 09 Jul 2025.
Copyright: © 2025 Duong, De Sarno, FAKIR, Bauman, Martinov, Thomson and Lee. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Thanh-Tai Duong, Western University, London, Canada
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