Radiopharmaceutical: An Update and Comparison of Preclinical Investigation Result of Alpha and Beta Emitter Radioisotope

Abstract: Radiopharmaceuticals are radioactive compounds used for diagnostic imaging and therapeutic purposes. In diagnostic, gamma emitters are commonly utilized. Conversely, radioisotopes employed for therapy are beta and alpha emitters, which generally have contrasting Linear Energy Transfer (LET) and tissue penetration profiles. These distinguishable characteristics allow for the complementary or improvement of radiopharmaceuticals. For instance, noticeable breakthroughs have been made with the approval of targeted beta-emitting radiopharmaceuticals using agents such as Lutathera ( 177 LuLu-DOTA-TATE) or Pluvicto ( 177 LuLu-PSMA-617). However, with the increase in isotope production and purification technology, new radiolabeling variations in multiple α-emitting particles have emerged. Preclinical investigation is a critical multi-step process to evaluate the safety and effectiveness of radiopharmaceuticals before being tested in humans with the purpose of translating these innovations into clinical practice. Accordingly, a narrative review was conducted on the preclinical investigation of radiopharmaceuticals to ensure positive direction for radiopharmaceuticals study. From this narrative review, notable results were obtained for actinium-225 and lead-212 based radiopharmaceuticals. From the perspective of targeted beta therapy, limited studies on terbium-161 have revealed that it is more potent than lutetium-177 with the same targeting molecules in the same animal models. It has been concluded that targeted alpha therapy is generally better than targeted beta therapy in many preclinical settings. Keywords: radiopharmaceuticals, targeted alpha therapy, targeted beta therapy, preclinical investigation