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In this study, the calibration factor necessary for quantitative SPECT analysis was derived by dividing the known activity concentration. For the dosimetric calculation, the STP voxel-based dosimetry using the Hanschied approach was employed to calculate the absorbed dose in the kidneys and tumours based on the SPECT images acquired approximately 48 hours after administration.

The mean and SD of kidney absorbed dose were 2.04 Gy ± 0.37 Gy (range 1.71 to 2.67 Gy). The absorbed doses within tumours showed considerable variation across the twenty-five tumours analysed, which were derived from eight treatment cycles. Tumour absorbed doses ranged from a low of 0.98 Gy to a high of 16.05 Gy. The mean absorbed dose to the tumours was 5.14 Gy, the SD was 3.81 Gy, as detailed in the box plot in Figure 3.

Quantitative voxel-based dosimetry was carried out for five patients (P1–P5) over eight treatment cycles (C1–C8), with imaging acquisition performed between 48 and 52 hours post-therapy. The absorbed radiation doses to the kidneys and selected tumour sites are summarised in Table 2.

Kidney absorbed dose

Across all patients, the kidney absorbed doses remained within a relatively narrow range, suggesting consistent radiopharmaceutical handling and organ tolerance. For Patient P1, who underwent three treatment cycles (C1–C3), the kidney dose started at 1.99 Gy in C1, rose to 2.66 Gy in C2, and then dropped slightly to 2.23 Gy in C3. This fluctuation may reflect changes in bio-distribution or renal clearance over time.

Patients P2 and P3, each evaluated during one or two cycles (C4–C6), had similar kidney doses, consistently measured at 1.71 Gy, despite variation in tumour load and lesion location. Patient P4 (C7) received 1.88 Gy, while Patient P5 (C8) had the highest kidney dose at 2.46 Gy. Notably, none of the patients exceeded the generally accepted renal threshold, supporting the safety of the administered activity levels in this cohort.

Tumour absorbed dose

Tumour dosimetry revealed a broader range of absorbed doses, reflecting both inter-patient and intra-patient variation. In Patient P1, lung lesions demonstrated a downward trend across three consecutive cycles, with the left lung receiving 8.54 Gy, 7.67 Gy, and 4.20 Gy in C1, C2, and C3, respectively. Similarly, the right lung showed a decrease from 5.92 Gy to 3.17 Gy. This decline likely indicates therapeutic response, consistent with expectations following multiple cycles of targeted radionuclide therapy (as illustrated in Figure 4).

A 64-year-old male with metastatic castration-resistant prostate cancer (mCRPC). Post ¹⁷⁷Lu-PSMA therapy showing a 1^st cycle in December 2023, b 2^nd cycle in March 2024, and c 3^rd cycle in June 2024. Whole-body SPECT/CT at 48 hours post-administration demonstrates good tracer uptake in multiple lungs, left adrenal, and bone metastases, with physiological uptake in salivary glands, liver, spleen, and bowel. Markings indicate a decrease in lung lesions across treatment cycles

Patient P2 showed tumour doses between 1.93 and 5.53 Gy in spinal and rib lesions. Though the absorbed doses remained moderate, a slight decrease was observed in the second cycle (C5), particularly in the rib and sternum, which may suggest early response to treatment or subtle changes in radiotracer uptake.

In Patient P3 (C6), tumour absorbed doses were lower and more uniform, ranging from 1.55 to 2.69 Gy, covering thoracic and lumbar vertebrae. In contrast, Patient P4 (C7) demonstrated a much higher dose to the lumbar spine, reaching 16.05 Gy, the highest tumour dose recorded in this study. Additional lesions in the lung and pelvis received 4.18 Gy and 3.76 Gy, respectively.

Patient P5 (C8) also presented with high skeletal uptake. The lumbar spine lesion received 13.00 Gy, while T-spine and pelvic lesions ranged from 6.03 to 10.03 Gy. These findings reflect intense PSMA expression in metastatic bone lesions and underline the heterogeneity of tumour dose distribution in advanced disease.