The Evolution of Molecular Imaging Radiopharmaceuticals

摘要

Molecular imaging may be defined as the noninvasive imaging at the molecular level of biological function in the living subject. While molecular imaging by optical, US, CT and MRI are relatively recent developments, nuclear molecular imaging using radioactive tracers was in practice in the 1940's with ~(131)I iodide for thyroid targeting and in the 1950's with a variety of additional molecular imaging agents labeled usually with ~(131)I but also with ~(203)Hg, ~(198)Au, ~(133)Xe, etc.. This presentation will briefly describe the steady evolution of radiopharmaceuticals for nuclear molecular imaging to the present but emphasizing the early years. The pioneers developing molecular imaging radiopharmaceuticals, in addition to not having the benefit of our knowledge of molecular medicine or our access to animal models and imaging devices, were often medical doctors presumably with limited chemical expertise. Thus the earliest molecular imaging radiopharmaceuticals were often established drugs such as Hippuran, albumin, triiodothyronine, etc. that were then radiolabeled. The radionuclide of choice was almost always ~(131)I primarily because the chemistry of iodine is relatively simple, although there were a few exceptions such as ~(75)Se-selenomethionine. The introduction of metallic radionuclides had to wait until the mid to late 1960's in part because of availability but more because of a limited understanding of the complex chemistry of metals. Both conditions improved rapidly as ~(113m)In and then ~(111)In began to replace ~(131)I. This process dramatically accelerated with the introduction of ~(99m)Tc in 1960. The almost ideal imaging properties of this radionuclide encouraged both an accelerated investigation of technetium chemistry and the commercialization of the ~(99)Mo generator. Thus ~(99m)Tc labeled pyrophosphate/polyphosphates/ phosphonates replaced ~(18)F for bone imaging, the ~(99m)Tc labeled IDAs replaced ~(131)I-Rose Bengal for hepatobiliary imaging, ~(99m)Tc-DTPA replaced ~(131)I-Renografin for renography, etc. The appearance of positron emitting molecular imaging agents in the 1970's owes its genesis to hot atom chemists who turned their attention to radiopharmaceuticals and synthesized of a number of agents labeled with ~(11)C such as glucose and with ~(18)F such as FDG.