Lesion dosimetry for [(177)Lu]Lu-PSMA-617 radiopharmaceutical therapy combined with stereotactic body radiotherapy in patients with oligometastatic castration-sensitive prostate cancer Journal Article

   

Authors:	Grkovski, M.; O'Donoghue, J. A.; Imber, B. S.; Andl, G.; Tu, C.; Lafontaine, D.; Schwartz, J.; Thor, M.; Zelefsky, M. J.; Humm, J. L.; Bodei, L.
Article Title:	Lesion dosimetry for [(177)Lu]Lu-PSMA-617 radiopharmaceutical therapy combined with stereotactic body radiotherapy in patients with oligometastatic castration-sensitive prostate cancer
Abstract:	A single-institution prospective pilot clinical trial was performed to demonstrate the feasibility of combining [177Lu]Lu-PSMA-617 radio-pharmaceutical therapy (RPT) with stereotactic body radiotherapy (SBRT) for the treatment of oligometastatic castration-sensitive prostate cancer. Methods: Six patients with 9 prostate-specific membrane antigen (PSMA)–positive oligometastases received 2 cycles of [177Lu]Lu-PSMA-617 RPT followed by SBRT. After the first intravenous infusion of [177Lu]Lu-PSMA-617 (7.46 6 0.15 GBq), patients underwent SPECT/CT at 3.2 6 0.5, 23.9 6 0.4, and 87.4 6 12.0 h. Voxel-based dosimetry was performed with calibration factors (11.7 counts per second/MBq) and recovery coefficients derived from in-house phantom experiments. Lesions were segmented on baseline PSMA PET/CT (50% SUVmax). After a second cycle of [177Lu]Lu-PSMA-617 (44 6 3 d; 7.50 6 0.10 GBq) and an interim PSMA PET/CT scan, SBRT (27 Gy in 3 fractions) was delivered to all PSMA-avid oligo-metastatic sites, followed by post-PSMA PET/CT. RPT and SBRT voxelwise dose maps were scaled (a/b 5 3 Gy; repair half-time, 1.5 h) to calculate the biologically effective dose (BED). Results: All patients completed the combination therapy without complications. No grade 31 toxicities were noted. The median of the lesion SUVmax as measured on PSMA PET was 16.8 (interquartile range [IQR], 11.6) (baseline), 6.2 (IQR, 2.7) (interim), and 2.9 (IQR, 1.4) (post). PET-derived lesion volumes were 0.4–1.7 cm3. The median lesion-absorbed dose (AD) from the first cycle of [177Lu]Lu-PSMA-617 RPT (ADRPT) was 27.7 Gy (range, 8.3–58.2 Gy; corresponding to 3.7 Gy/GBq, range, 1.1–7.7 Gy/GBq), whereas the median lesion AD from SBRT was 28.1 Gy (range, 26.7–28.8 Gy). Spearman rank correlation, r, was 0.90 between the baseline lesion PET SUVmax and SPECT SUVmax (P 5 0.005), 0.74 (P 5 0.046) between the baseline PET SUVmax and the lesion ADRPT, and 20.81 (P 5 0.022) between the lesion ADRPT and the percent change in PET SUVmax (baseline to interim). The median for the lesion BED from RPT and SBRT was 159 Gy (range, 124–219 Gy). r between the BED from RPT and SBRT and the percent change in PET SUVmax (baseline to post) was 20.88 (P 5 0.007). Two cycles of [177Lu]Lu-PSMA-617 RPT contributed approximately 40% to the maximum BED from RPT and SBRT. Conclusion: Lesional dosimetry in patients with oligometastatic castration-sensitive prostate cancer undergoing [177Lu]Lu-PSMA-617 RPT followed by SBRT is feasible. Combined RPT and SBRT may provide an efficient method to maximize the delivery of meaningful doses to oligometastatic disease while addressing potential microscopic disease reservoirs and limiting the dose exposure to normal tissues. © 2023 by the Society of Nuclear Medicine and Molecular Imaging.
Keywords:	adult; clinical article; aged; middle aged; clinical trial; radiation dose; prospective study; prospective studies; radiopharmaceuticals; prostate specific antigen; multiple cycle treatment; anemia; tumor volume; pathology; prostate cancer; prostate-specific antigen; prostate specific membrane antigen; correlation coefficient; pilot study; dosimetry; radiosurgery; radiopharmaceutical agent; hyperbilirubinemia; castration; stereotactic body radiation therapy; biologically effective dose; sbrt; castration resistant prostate cancer; dipeptides; clinical outcome; single heterocyclic rings; heterocyclic compounds, 1-ring; lutetium; oligometastasis; maximum standardized uptake value; dipeptide; humans; human; male; article; prostatic neoplasms, castration-resistant; positron emission tomography-computed tomography; positron emission tomography computed tomography; single photon emission computed tomography-computed tomography; effective dose (radiation); metastatic castration sensitive prostate cancer; psma-617; vipivotide tetraxetan lutetium lu 177; [<sup>177</sup>lu]lu-psma-617; oligometastatic castration sensitive prostate cancer
Journal Title:	Journal of Nuclear Medicine
Volume:	64
Issue:	11
ISSN:	0161-5505
Publisher:	Society of Nuclear Medicine
Date Published:	2023-11-01
Start Page:	1779
End Page:	1787
Language:	English
DOI:	10.2967/jnumed.123.265763
PUBMED:	37652541
PROVIDER:	scopus
PMCID:	PMC10626375
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85175993618&doi=10.2967%2fjnumed.123.265763&partnerID=40&md5=785d2a0cd980cbb24a8900929a00f2c1
Notes:	Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PDF -- MSK corresponding author is Milan Grkovski -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/211443