Abstract
INTRODUCTION: We have previously shown that copper-64 ((64)Cu)-DOTHA(2)-PSMA can be used for positron emission tomography (PET) imaging of prostate cancer. Owing to the long-lasting, high tumoral uptake of (64)Cu-DOTHA(2)-PSMA, the objective of the current study was to evaluate the therapeutic potential of (64)Cu-DOTHA(2)-PSMA in vivo. METHODS: LNCaP tumor-bearing NOD-Rag1(null)IL2rg(null) (NRG) mice were treated with an intraveinous single-dose of (64)Cu-DOTHA(2)-PSMA at maximal tolerated injected activity, (nat)Cu-DOTHA(2)-PSMA at equimolar amount (control) or lutetium-177 ((177)Lu)-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 (64)Cu-DOTHA(2)-PSMA than with (nat)Cu-DOTHA(2)-PSMA (p < 0.001). Likewise, survival was also longer when compared to (177)Lu-PSMA-617, although it did not reach statistical significance (p = 0.09). RBCs counts remained within normal range for the (64)Cu-DOTHA(2)-PSMA group. (64)Cu-DOTHA(2)-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 (64)Cu-DOTHA(2)-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.