The phase 2 LUNAR trial randomized (1:1) patients with oligorecurrent hormone-sensitive prostate cancer to neoadjuvant [177Lu]Lu-PSMA-I&T (2 cycles, 6.8 GBq) followed by stereotactic body radiotherapy (SBRT) versus SBRT alone.
[177Lu]Lu-PSMA-I&T before SBRT was well tolerated and significantly improved PSMA PET/CT-based progression-free survival compared with SBRT alone. Here, we report the estimated absorbed doses (AD) of [177Lu]Lu-PSMA-I&T to organs at risk and lesions. Methods: This analysis was conducted on all 45 patients randomized to the investigational arm. Quantitative SPECT/CT images were acquired at 4, 24, and 72-96 h postinjection of cycle 1. Kidneys, salivary and lacrimal glands, and liver were delineated with deep learning-assisted segmentation, whereas lumbar vertebrae were manually segmented as a surrogate for bone marrow. Planned target volumes were transferred from the SBRT plans to the SPECT/CT series. Registration between time points was manually verified for each segmentation. ADs were estimated using a multiple-time-point voxel-based schema. Time-activity data were fit using a monoexponential function. Partial-volume effects were corrected using volume-specific phantom-based recovery coefficients. Results: In the 45 patients included, the median prostate-specific antigen was 1.10 ng/mL (range, 0.16-14.70 ng/mL). In total, 123 lesions total were identified, with a median per patient of 2 (range, 1-9). Median whole-body total tumor volume was 14.5 cm3 (range, 1.9-145.9 cm3). Median SUVmax on baseline PSMA PET/CT and 24-h SPECT/CT was 3.49 (range, 0.59-45.30) and 0.72 (range, 0.02-34.24), respectively. The AD to the kidneys, parotids, submandibulars, lacrimals, liver, and bone marrow were 0.35 ± 0.10, 0.20 ± 0.10, 0.24 ± 0.10, 0.70 ± 0.49, 0.03 ± 0.01, and 0.005 ± 0.002 Gy/GBq, respectively. The mean dose to bone (n = 38), lymph node (n = 82), and soft tissue (n = 3) lesions were 0.19 ± 0.42, 0.46 ± 0.81, and 0.30 ± 0.38 Gy/GBq, respectively. Conclusion: The ADs from [177Lu]Lu-PSMA-I&T to organs at risk were consistent with prior reports, supporting the safety in patients with oligorecurrent hormone-sensitive prostate cancer. There was substantial heterogeneity in lesion AD estimates on both inter- and intrapatient levels. Because of the limited spatial resolution of SPECT, partial-volume effects can underestimate the AD in small volumes. Nevertheless, 2 neoadjuvant cycles of [177Lu]Lu-PSMA-I&T before SBRT prolonged progression-free survival, consistent with effective treatment of occult disease beyond imaging detectability.
Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2026 Apr 02 [Epub ahead of print]
Zachary Ells, Catherine Meyer, Koichiro Kimura, Holly Wilhalme, Minsong Cao, Vinicius B Ludwig, Lena M Unterrainer, David Sennung, Rejah Nabong, Carol Felix, Luca F Valle, Anthony Daley, Johannes Czernin, Magnus Dahlbom, Amar U Kishan, Jeremie Calais
Department of Nuclear Medicine and Theranostics, Ahmanson Translational Theranostics Division, David Geffen School of Medicine, UCLA, Los Angeles, California; ., Department of Nuclear Medicine and Theranostics, Ahmanson Translational Theranostics Division, David Geffen School of Medicine, UCLA, Los Angeles, California., Department of Medicine Statistical Core, UCLA, Los Angeles, California., Department of Radiation Oncology, UCLA, Los Angeles, California; and.