Post-therapeutic dosimetry of Lu-177-DKFZ-PSMA-617 in the treatment of patients with metastatic castration-resistant prostate cancer

摘要

Objective(177)Lu-DKFZ-PSMA-617, a urea-based compound, binds to the extracellular domain of prostate-specific membrane antigen, thus providing an effective target for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Before its therapeutic use, it is necessary that the radiation dosimetry of this radiopharmaceutical be studied to determine the safe activity that can be administered in patients to prevent haematological, renal and liver toxicity. The present study thus aimed to assess the pharmacokinetics and dosimetry of Lu-177-DKFZ-PSMA-617 in CRPC patients.Materials and methodsAfter obtaining ethical clearance from the institute ethics review board, we enrolled mCRPC patients who were positive on a Glu-NH-CO-NH-Lys-(Ahx)-[Ga-68(HBED-CC)] PET/CT scan. For kidney protection, a cocktail of lysine and arginine diluted in 2 litres of normal saline was infused, starting from 30 to 60min before Lu-177-DKFZ-PSMA-617 infusion. The mean administered activity in the overall population was 2.521.3GBq. For the purpose of dosimetry, each patient underwent nine planar whole-body scans along with blood and urine sample collection at 0.5, 3.5, 24, 48, 72, 96, 120, 144 and 168h, respectively. SPECT/CT was performed to derive the volume of salivary glands (parotid and submandibular glands) and tumour. Dosimetric evaluation was carried out using the OLINDA/EXM 1.0 software.ResultsA total of 26 mCRPC patients with a mean age of 66.30 +/- 9.95 years (range: 38-81 years) were recruited. Normal physiological uptake was observed in all the patients in the lacrimal glands, salivary glands (parotid glands and submandibular glands), liver, spleen, kidneys, intestines and urinary bladder. Organs with the highest absorbed doses were the salivary glands, followed by the kidneys, receiving 1.24 +/- 0.26 and 0.99 +/- 0.31mGy/MBq, respectively. The mean absorbed doses to the liver, urinary bladder and red marrow were 0.36 +/- 0.10, 0.243 +/- 0.09 and 0.048 +/- 0.05mGy/MBq, respectively. The mean whole-body dose was 0.016 +/- 0.003mGy/MBq.Conclusion(177)Lu-DKFZ-PSMA-617 therapy is a safe option in the treatment of mCRPC patients.