Differential Clearance of [ 177 Lu]Lu-PSMA-617 from Metastatic Prostate Cancer Lesions and Normal Tissues creates a Window for Safe Application of DNA Repair Inhibitors
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Background
DNA repair inhibitors may safely enhance targeted radiotherapy if they can be administered when radioisotope has cleared from critical normal tissues. We investigated whether the kinetics of [ 177 Lu]Lu-PSMA-617 (Pluvicto) would be consistent with such a strategy in metastatic castrate resistant prostate cancer (mCRPC).
Materials and Methods
Pluvicto effective t 1/2 was measured for organs-at-risk (kidneys, parotid and submandibular glands) and lesions from 60 mCRPC patients. Based on this, a safe strategy for DDR inhibition was defined, and its potential benefit to the lesion was calculated, using published in vitro radiosensitivity data.
Results
Pluvicto clearance is almost 3× faster in normal organs-at-risk compared to lesions. Using pre-clinical estimates of DDRi sensitization, a meaningful increase in lesion effective treatment dose could be achieved with minor additional risk to normal organs.
