Cyclotron-Based Radiopharmaceuticals for Nuclear Medicine Therapy

Abstract

New radionuclides, used for targeted radionuclide therapy, can be produced by cyclotrons dedicated to nuclear medicine and which have become common. Among beta particle emitting radionuclides, copper-67 has favorable physical and biochemical properties. Its halflife of 2.58 days is well matched to the pharmacokinetics of F(ab’)2 antibody fragments and the energy of emitted electrons corresponds to a short path length that fits the size of disseminated clusters of malignant cells. But production of this radionuclide requires a high energy/high intensity cyclotron which limits its availability. Scandium-47 has favorable physical properties but also requires high proton energy cyclotron which explains its poor availability. Among alpha-emitting radionuclides which seem to be optimal for killing of isolated tumor cells due to the short path length and high linear energy transfer (LET) of emitted alpha particles, astatine-211 has attracted much interest because of a longer half-life (7.2 h) than that of bismuth-213 or bismuth-212 which have also been tested in preclinical and clinical studies. Actinium-225 which can be produced by proton irradiation of radium-226 and bismuth-213 have been proposed years ago for targeted radionuclide therapy. Actinium-225 has been presented as an « atomic nanogenerator » due to a cascade of radioactive daughters emitting four alpha particles per actinium-225 atom. Bismuth-213 has been used one decade ago for labeling of a humanized anti-CD33 antibody in a phase I clinical study in patients with acute myelogenous antibody. Finally terbium-149 with a half-life of 4.1 h is another alternative alpha-emitting radionuclide and has been used in a few preclinical studies. Radionuclides which emit Auger electrons such as indium-111 may be highly toxic if delivered in or close to nucleus of tumor cells. Thus today there is a real need for production of innovative radionuclides by cyclotrons to improve efficacy of targeted radionuclide therapy.