Dive into the details of radionuclide antibody conjugates: what role do EPR effects and LETs of different radionuclides play?

Radionuclide antibody conjugate (RAC) is a promising diagnostic and therapeutic tool. It combines radionuclides and antibodies by connecting arms and chelating agents, offering precise targeting and potent killing of tumor cells. However, further development and optimization of this radiopharmaceutical is needed to enhance the ultimate substantive efficacy for clinical translation. In this issue of AJNMMI, Strand et al. evaluated the enhanced permeability effect and different linear energy transfer (LET) of radionuclides in a prostate cancer xenograft model. The results showed that specific targeting might negatively influence normal organ uptake when targeting secreted antigens and different LETs of radionuclides might have diverse effects on receptor expression and cell proliferation in tumors. The findings provide new thinking for the development of antibody-based radiopharmaceuticals.