Abstract
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Purpose: Prostate cancer can be targeted by ligands to the prostate-specifc membrane antigen (PSMA). In this study, we conjugated a truncated Evans Blue (EB) molecule and DOTA chelator onto PSMA-617 (EB-PSMA-617) and labeled it with 177Lu to increase the tumor accumulation and retention for radioligand therapy. The purpose of this study was to assess the safety and measure image-based absorbed dose of 177Lu-EB-PSMA-617 in patients with metastatic castration-resistant prostate cancer (mCRPC) who will undergo radioliagnd therapy using 177Lu-EB-PSMA-617. Methods: With institutional review board approval and informed consent, 4 patients with progressive prostate cancer with a mean age of 72.3±2.9 years were recruited. All patients underwent whole-body 68Ga-PSMA PET/CT for selection and accepted intravenous injection with single dose 0.80-1.1 GBq (21.5-30 mCi) of 177Lu-EB-PSMA-617 within one week, then monitored at 2, 24, 72, 120 and 168 h after 177Lu-EB-PSMA617 administration with serial whole body planar and SPECT/CT imaging. Blood samples were collected on 20, 40, 60, and 120 min, and daily afterwards. The blood activity was expressed in percentage of the injected dose (%IA). Hematologic status, liver function, and renal function were documented before and at one week after the injection of 177Lu-EB-PSMA-617. Dosimetric evaluation was carried out using the OLINDA/EXM 1.0 software. Results: All patients tolerated the administered activity without any acute adverse effects. Normal physiological uptake was observed in all the patients in the kidneys, liver, spleen, salivary glands, intestines and urinary bladder. The mean whole-body effective dose was 0.08 ± 0.01 mSv/MBq. The effective doses were 0.97 ± 0.17 mSv/MBq for the kidneys; 0.40 ± 0.12 mSv/MBq for the liver; 0.46 ± 0.02 mSv/MBq for the spleen, and 0.07 ± 0.03 mSv/MBq for the red marrow. The mean value of %IA in the blood was reduced to 7.6% within the first 2 h and then to 2.4% at 24 h after injection. High and extended accumulation of 177Lu-EB-PSMA-617 was observed in all patients with a SUVmean of 5.75 ± 1.08 at 2 h p.i. and 24.52 ± 10.95 at 7d p.i.. Conclusion: High and extended tumor accumulation of 177Lu-EB-PSMA-617 was achieved by EB modification. 177Lu-EB-PSMA is a safe and promising treatment option for mCRPC patients with the kidneys and red marrow representing the critical organs. Figure legend: Figure 1. 68Ga-PSMA617 PET/CT maximum intensity projection image of a patient (A) , 177Lu-EB-PSMA617 whole-body images (B) and SUV for various organs and lesions (C) obtained at different time points post-injection. Figure 2. Mean absorbed doses (mSv/MBq) of 177Lu-EB-PSMA617 in patients with castration-resistant prostate cancer.
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