Outcome-driven dosimetry optimization for [177Lu]Lu-PSMA-617 radiopharmaceutical therapy: proof of concept on single time point dosimetry optimization.
Publisher DOI
PubMed ID
42287389
Abstract
Purpose
Internal dosimetry in radiopharmaceutical therapy (RPT) traditionally prioritizes methodological optimization driven by physical dose accuracy. However, even recommended multiple-time-point (MTP) dosimetry remains subject to uncertainties related to limited sampling schedules, pharmacokinetic, and curve-fitting modeling assumptions. In patients with metastatic castration-resistant prostate cancer (mCRPC) treated with [177Lu]Lu-PSMA-617 RPT, we explored an outcome-driven dosimetry optimization strategy by comparing MTP and single-time-point (STP) dosimetry, and identifying optimal time-points (TPs) for Hänscheid approximation based on therapy outcomes.Methods
Clinical and image data from 50 patients were retrospectively analyzed. Transient treatment-emergent adverse events (TEAEs) and prostate-specific antigen (PSA) response were monitored following CTCAE v5.0 and PCWG3. Cycle-level mean absorbed doses (MTPDtox, and 1d-, 2d-, 3d-STPDtox based on single SPECT acquisitions at 1-, 2-, 3-day(s) p.i.) were computed for organs-at-risk and whole-body tumors. Additionally, cumulative absorbed doses (STPDcum & MTPDcum) were derived for whole-body tumors.Results
Bone marrow STP dosimetry correlated significantly with anaemia grading (1d-STPDtox: Spearman's ρ=0.35;2d-STPDtox: Spearman's ρ=0.41; 3d-STPDtox: Spearman's ρ=0.46; all padj<0.001), aligning with MTPDtox (Spearman's ρ=0.43, p<0.001). Williams' F-test confirmed no significant difference in correlation strength between STPDtox & MTPDtox derived correlations at any TPs. For PSA response, both MTPDcum (Spearman's ρ=-0.26, padj<0.05) and STPDcum (1d-&2d-STPDcum: Spearman's ρ=-0.34, padj<0.001) showed significant correlations, without statistically significant differences between STPDcum & MTPDcum derived correlations.Conclusion
The outcome-driven TP selection for Hänscheid-based STP dosimetry converges with the physics-based choice within 2-day p.i., the clinically driven approach offers an alternative and complementary strategy for dosimetry development and may facilitate its translation into clinical practice.
Internal dosimetry in radiopharmaceutical therapy (RPT) traditionally prioritizes methodological optimization driven by physical dose accuracy. However, even recommended multiple-time-point (MTP) dosimetry remains subject to uncertainties related to limited sampling schedules, pharmacokinetic, and curve-fitting modeling assumptions. In patients with metastatic castration-resistant prostate cancer (mCRPC) treated with [177Lu]Lu-PSMA-617 RPT, we explored an outcome-driven dosimetry optimization strategy by comparing MTP and single-time-point (STP) dosimetry, and identifying optimal time-points (TPs) for Hänscheid approximation based on therapy outcomes.Methods
Clinical and image data from 50 patients were retrospectively analyzed. Transient treatment-emergent adverse events (TEAEs) and prostate-specific antigen (PSA) response were monitored following CTCAE v5.0 and PCWG3. Cycle-level mean absorbed doses (MTPDtox, and 1d-, 2d-, 3d-STPDtox based on single SPECT acquisitions at 1-, 2-, 3-day(s) p.i.) were computed for organs-at-risk and whole-body tumors. Additionally, cumulative absorbed doses (STPDcum & MTPDcum) were derived for whole-body tumors.Results
Bone marrow STP dosimetry correlated significantly with anaemia grading (1d-STPDtox: Spearman's ρ=0.35;2d-STPDtox: Spearman's ρ=0.41; 3d-STPDtox: Spearman's ρ=0.46; all padj<0.001), aligning with MTPDtox (Spearman's ρ=0.43, p<0.001). Williams' F-test confirmed no significant difference in correlation strength between STPDtox & MTPDtox derived correlations at any TPs. For PSA response, both MTPDcum (Spearman's ρ=-0.26, padj<0.05) and STPDcum (1d-&2d-STPDcum: Spearman's ρ=-0.34, padj<0.001) showed significant correlations, without statistically significant differences between STPDcum & MTPDcum derived correlations.Conclusion
The outcome-driven TP selection for Hänscheid-based STP dosimetry converges with the physics-based choice within 2-day p.i., the clinically driven approach offers an alternative and complementary strategy for dosimetry development and may facilitate its translation into clinical practice.
Date Issued
2026-06-13
Publication Type
Article
Subject(s)
Subjects
Dosimetry
•
Prostate cancer
•
Radiopharmaceutical therapy
•
Theranostics
•
[ 177 Lu]Lu-PSMA-617
Language(s)
en
Author(s)
Additional Credits
Journal
European Journal of Nuclear Medicine and Molecular Imaging
Publisher
Springer
ISSN
1619-7089
1619-7070
Access(Rights)
open.access