68Ga-DOTA-DiPSMA PET/CT Imaging: Biodistribution, Dosimetry, and Preliminary Application in Prostate Cancer.

Jiaying Zhang,Zefang Lin,Weibing Miao,Shaobo Yao,Rong Lin,Xiaojun Zhang,Mengchao Cui

doi:10.3389/fbioe.2021.811972

Abstract

Purpose: This prospective trial aimed to evaluate the safety, dosimetry, and biodistribution of a novel theranostic probe 68Ga-DOTA-DiPSMA. Also, we have performed the first preliminary application with 68Ga-DOTA-DiPSMA in prostate cancer (PCa) patients. Methods: Five healthy volunteers and ten PCa patients were injected with an intravenous bolus of 68Ga-DOTA-DiPSMA. They received serial whole-body PET scans from the time of injection up to 60 min post-injection, with a second PET/CT scanning at 120 min post-injection. In PCa patients, low-dose CT scan and whole-body PET were performed with 2 min per bed position in 40 min post-injection. Absorbed organ doses and effective doses were calculated using OLINDA/EXM. Normal organ uptake and tumor lesion uptake were measured. A lesion-by-lesion analysis was performed. Results: 68Ga-DOTA-DiPSMA administration was safe and well-tolerated. The kidneys received the highest absorbed dose (114.46 ± 29.28 μSv/MBq), followed by the urinary bladder wall (100.82 ± 46.22 μSv/MBq) in accordance with the expected Prostate-Specific Membrane Antigen (PSMA) renal excretion of the tracer. The mean effective dose was 19.46 ± 1.73 μSv/MBq. The SUVmax of 68Ga-DOTA-DiPSMA PET/CT for PCa lesions, bone metastases, and lymph node metastases was 4.41 ± 2.72, 2.95 ± 1.11, and 3.26 ± 1.20, respectively. Conclusion: Injection of 68Ga-DOTA-DiPSMA is safe and associated with low absorbed and effective doses. 68Ga-DOTA-DiPSMA shows favorable kinetics and imaging characteristics in patients who warrant further head-to-head comparison to validate 68Ga-DOTA-DiPSMA as an alternative for gallium-68-labeled PSMA clinical PET. Low nonspecific uptake in normal organs of 68Ga-DOTA-DiPSMA indicates potential radioligand therapy (RLT) application when labeled with 177Lu, 90Y, or 225Ac.

Highlights

Prostate cancer (PCa) is one of the most frequently diagnosed cancers in men and the lethal malignant diseases leading to male cancer-related death worldwide (Attard et al, 2016)
We have discovered a new PSMA dimer (DOTA-DiPSMA, Figure 1)
We aimed to evaluate the safety, biodistribution, and dosimetry of 68Ga-DOTA-DiPSMA in healthy volunteers and its diagnostic efficacy in PCa patients

Summary

Introduction

Prostate cancer (PCa) is one of the most frequently diagnosed cancers in men and the lethal malignant diseases leading to male cancer-related death worldwide (Attard et al, 2016). The accurate presence and location of primary or recurrent tumors are critical for planning effective patient management (Mottet et al, 2021). Prostate biopsy is the definitive way to confirm PCa (Attard et al, 2016). Multiple needle biopsies will increase the positive rate of lesion determination significantly. It is difficult to determine distant metastases and increase the risk of complications resulting from biopsy operation (Attard et al, 2016). There has been an unmet need for more advanced imaging modalities to determine primary and metastatic lesions that can be helpful to PCa patient management (observation, salvage local therapy, and systemic therapy). PET with 18F-FDG is effective for most malignant tumors, but it lacks sensitivity for PCa. it is urgent to discover new nuclear medicine imaging agents with more specificity for PCa

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