An Intrapatient Dosimetry Comparison of177Lu-rhPSMA-10.1 and177Lu-PSMA-I&T in Patients with Metastatic Castration-Resistant Prostate Cancer

As the use of radioligand therapy moves earlier in the prostate cancer timeline, minimizing the absorbed dose to normal organs while maintaining high tumor radiation doses becomes more clinically important because of the longer life expectancy of patients. We performed an intrapatient comparison of pretherapeutic dosimetry with the novel radiohybrid prostate-specific membrane antigen–targeting radiopharmaceutical ¹⁷⁷Lu-rhPSMA-10.1, along with ¹⁷⁷Lu-PSMA-I&T, in patients with metastatic castration-resistant prostate cancer. Methods: Four consecutive patients with advanced histologically proven metastatic castration-resistant prostate cancer who were scheduled for radioligand therapy were evaluated. Before undergoing therapy, each patient received 1.06 ± 0.05 GBq of ¹⁷⁷Lu-rhPSMA-10.1 and 1.09 ± 0.02 GBq of ¹⁷⁷Lu-PSMA-I&T at least 7 d apart. For dosimetric assessment, whole-body planar scintigraphy was performed after 5 min, 4 h, 1 d, 2 d, and 7 d. In addition, SPECT/CT images were acquired over the thorax and the abdomen, 4 h, 1 d, 2 d, and 7 d after injection. Dosimetry of the whole body and salivary glands was based on the evaluation of the counts in whole-body planar imaging. Dosimetry of the kidneys, liver, spleen, bone marrow, and tumor lesions (≤4 per patient) was based on the activity in volumes drawn on SPECT/CT images. Doses were calculated using OLINDA/EXM version 1.0. The therapeutic index (TI), or ratio between mean dose of the metastases and mean dose of the kidneys, was calculated for each patient. Results: We found the dose to the kidneys to be higher with ¹⁷⁷Lu-rhPSMA-10.1 than with ¹⁷⁷Lu-PSMA-I&T (0.68 ± 0.30 vs. 0.46 ± 0.10 mGy/MBq); however, ¹⁷⁷Lu-rhPSMA-10.1 delivered an average of a 3.3 times (range, 1.2–8.3 times) higher absorbed radiation dose to individual tumor lesions. Consequently, intraindividual comparison revealed a 1.1–3.1 times higher TI for ¹⁷⁷Lu-rhPSMA-10.1 than for ¹⁷⁷Lu-PSMA-I&T in all evaluated patients. The effective whole-body dose was 0.038 ± 0.008 mSv/MBq for ¹⁷⁷Lu-rhPSMA-10.1 and 0.022 ± 0.005 mSv/MBq for ¹⁷⁷Lu-PSMA-I&T. Conclusion: Using ¹⁷⁷Lu-rhPSMA-10.1 can significantly increase the tumor-absorbed dose and improve the TI compared with ¹⁷⁷Lu-PSMA-I&T. An improved TI gives the flexibility to maximize tumor-absorbed doses up to a predefined renal dose limit or, in earlier disease, to reduce the radiation exposure to the kidney while still achieving an effective tumor dose. The function of at-risk organs such as the kidneys is being assessed in a prospective clinical trial.