Guerard F, Barbet J, Chatal J F, Kraeber-Bodere F, Cherel M, Haddad F
Groupement d'Intérêt Public Arronax, University of Nantes, Nantes, France -
Q J Nucl Med Mol Imaging. 2015 Jun;59(2):161-7. Epub 2015 Mar 10.
Beta-emitting radionuclides are not able to kill isolated tumor cells disseminated in the body, even if a high density of radiolabeled molecules can be targeted at the surface of these cells because the vast majority of emitted electrons deliver their energy outside the targeted cells. Alpha-particle emitting radionuclides may overcome this limitation. It is thus of primary importance to test and validate the radionuclide of choice, the most appropriate carrier molecule and the most promising clinical indication. Four α-particle emitting radionuclides have been or are clinically tested in phase I studies namely 213Bi, 225Ac, 212Pb and 211At. Clinical safety has been documented and encouraging efficacy has been shown for some of them (213Bi and 211At). 211At has been the most studied and could be the most promising radionuclide but 225Ac and 212Pb are also of potential great interest. Any carrier molecule that has been labeled with β-emitting radionuclides could be labeled with alpha particle-emitting radionuclide using, for some of them, the same chelating agents. However, the physical half-life of the radionuclide should match the biological half-life of the radioconjugate or its catabolites. Finally everybody agrees, based on the quite short range of alpha particles, on the fact that the clinical indications for alpha-immunotherapy should be limited to the situation of disseminated minimal residual diseases made of small clusters of malignant cells or isolated tumor cells.
发射β射线的放射性核素无法杀死散布在体内的孤立肿瘤细胞，即使大量放射性标记分子能够靶向这些细胞表面，因为绝大多数发射出的电子会在靶向细胞外部释放能量。发射α粒子的放射性核素可能会克服这一限制。因此，测试和验证所选的放射性核素、最合适的载体分子以及最有前景的临床适应症至关重要。四种发射α粒子的放射性核素已在或正在进行I期临床试验，即213Bi、225Ac、212Pb和211At。已记录了临床安全性，其中一些（213Bi和211At）显示出了令人鼓舞的疗效。211At是研究最多的，可能是最有前景的放射性核素，但225Ac和212Pb也具有潜在的重大意义。任何已用发射β射线的放射性核素标记的载体分子，其中一些可使用相同的螯合剂用发射α粒子的放射性核素进行标记。然而，放射性核素的物理半衰期应与放射性缀合物或其代谢物的生物半衰期相匹配。最后，基于α粒子的射程相当短这一事实，大家都一致认为，α免疫疗法的临床适应症应仅限于由小簇恶性细胞或孤立肿瘤细胞构成的播散性微小残留病情况。
