Dataset Information

Theranostic ⁶⁴Cu-DOTHA₂-PSMA allows low toxicity radioligand therapy in mice prostate cancer model.

ABSTRACT:

Introduction

We have previously shown that copper-64 (⁶⁴Cu)-DOTHA₂-PSMA can be used for positron emission tomography (PET) imaging of prostate cancer. Owing to the long-lasting, high tumoral uptake of ⁶⁴Cu-DOTHA₂-PSMA, the objective of the current study was to evaluate the therapeutic potential of ⁶⁴Cu-DOTHA₂-PSMA in vivo.

Methods

LNCaP tumor-bearing NOD-Rag1^nullIL2rg^null (NRG) mice were treated with an intraveinous single-dose of ⁶⁴Cu-DOTHA₂-PSMA at maximal tolerated injected activity, ^natCu-DOTHA₂-PSMA at equimolar amount (control) or lutetium-177 (¹⁷⁷Lu)-PSMA-617 at 120 MBq to assess their impact on survival. Weight, well-being and tumor size were followed until mice reached 62 days post-injection or ethical limits. Toxicity was assessed through weight, red blood cells (RBCs) counts, pathology and dosimetry calculations.

Results

Survival was longer with ⁶⁴Cu-DOTHA₂-PSMA than with ^natCu-DOTHA₂-PSMA (p < 0.001). Likewise, survival was also longer when compared to ¹⁷⁷Lu-PSMA-617, although it did not reach statistical significance (p = 0.09). RBCs counts remained within normal range for the ⁶⁴Cu-DOTHA₂-PSMA group. ⁶⁴Cu-DOTHA₂-PSMA treated mice showed non-pathological fibrosis and no other signs of radiation injury. Human extrapolation of dosimetry yielded an effective dose of 3.14 × 10^-2 mSv/MBq, with highest organs doses to gastrointestinal tract and liver.

Discussion

Collectively, our data showed that ⁶⁴Cu-DOTHA₂-PSMA-directed radioligand therapy was effective for the treatment of LNCaP tumor-bearing NRG mice with acceptable toxicity and dosimetry. The main potential challenge is the hepatic and gastrointestinal irradiation.

SUBMITTER: Milot MC

PROVIDER: S-EPMC9889868 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

Theranostic 64Cu-DOTHA2-PSMA allows low toxicity radioligand therapy in mice prostate cancer model.

Milot Marie-Christine MC Bélissant-Benesty Ophélie O Dumulon-Perreault Véronique V Ait-Mohand Samia S Geha Sameh S Richard Patrick O PO Rousseau Étienne É Guérin Brigitte B

Frontiers in oncology 20230118

<h4>Introduction</h4>We have previously shown that copper-64 (64Cu)-DOTHA2-PSMA can be used for positron emission tomography (PET) imaging of prostate cancer. Owing to the long-lasting, high tumoral uptake of 64Cu-DOTHA2-PSMA, the objective of the current study was to evaluate the therapeutic potential of 64Cu-DOTHA2-PSMA in vivo.<h4>Methods</h4>LNCaP tumor-bearing NOD-Rag1nullIL2rgnull (NRG) mi ...[more]

PMID: 36741017

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