PSMA-targeted radioligand therapy with [177Lu]Lu-LNC1011 for metastatic castration-resistant prostate cancer: a pilot study

Background Preclinical studies have shown that the long-acting PSMA-targeting radiopharmaceutical [Lu-177]Lu-LNC1011 based on dansylated amino acid modification had high tumor uptake and prolonged retention. This study aimed to explore its safety and efficacy in patients with metastatic castration-resistant prostate cancer (mCRPC). Methods Eight mCRPC patients who met the inclusion criteria received intravenous treatment with [Lu-177]Lu-LNC1011. Treatment was repeated every 6 weeks for up to a maximum of 6 cycles. Molecular imaging and hematology markers were the main evaluation indicators. The primary endpoints were biochemical (PSA) response and molecular imaging response. Toxicity grading was assessed using the Common Terminology Criteria for Adverse Events version 5.0. Results Hematological toxicity was the primary side effect. In all patients, adverse events (AEs) after [Lu-177]Lu-LNC1011 treatment were primarily characterized by decreased levels of hemoglobin, white blood cells and platelets. Grade 3 anemia was recorded in 1 patient, and grade 2 leukopenia and thrombocytopenia were recorded in 4 patients. The average systemic effective dose was 0.18 mSv/MBq, and the kidney was the organ with the highest absorbed dose (3.11 +/- 0.26 mSv/MBq). Long half-life (71.30 +/- 8.23 h) and high absorbed dose [5.77, (range 5.5-14 Gy/GBq)] were calculated in the lesions. All patients had a more than 50% decline of PSA during treatment, and one patient dropped to 0 ng/mL. According to assessment criteria adapted from the PERCIST v.1.0 criteria, complete response, partial response, and disease progression were observed in 2 (25%), 4 (50%), and 2 (25%) patients, respectively. Conclusion [Lu-177]Lu-LNC1011 was well tolerated and had acceptable side effects for PSMA-targeted radioligand therapy. Tumor lesions received high radiation doses and had excellent responses to the treatment. Dose escalation studies in a larger number of patients are worth pursuing and necessary to confirm these results. URL of registry https://clinicaltrials.gov/study/NCT06809426?term=NCT06809.