Dosimetry Analysis of ¹⁷⁷ Lu-PSMA-I&T in Patients with Low-Volume Oligometastatic Hormone-Sensitive Prostate Cancer: A Secondary Analysis of the LUNAR Trial

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.