Recent Advances in Copper Radiopharmaceuticals

Abstract

Copper has five radioisotopes ((60)Cu, (61)Cu, (62)Cu, (64)Cu, and (67)Cu) that can be used in copper radiopharmaceuticals. These radioisotopes decay by mixed emissions of β+, β-, and γ with a wide range of half-lives from 9.74 min ((62)Cu) to 2.58 d ((67)Cu), which enable the design and synthesis of a variety of radiopharmaceuticals for different biomedical applications in diagnostic and therapeutic nuclear medicine. However, due to the availability and production cost, the research efforts in copper radiopharmaceuticals are mainly focused on the use of (64)Cu (t(1/2) = 12.7 h; 17.4% β+, 43% EC, 39% β-), a radioisotope with low positron energy (E β+max = 0.656 MeV) that is ideal for positron emission tomography (PET) imaging quantification and β- emissions along with Auger electron for radiotherapy. Driven by the ever-increasing availability of preclinical and clinical PET scanners, a considerable interest has been seen in the development of novel copper radiopharmaceuticals in the past decade for a variety of diseases as represented by PET imaging of cancer. To avoid unnecessary literature redundancy, this review focuses on the unrepresented research aspects of copper chemistry (e.g. electrochemistry) and their uses in the evaluation of novel nuclear imaging probe design and recent advances in the field towards the practical use of copper radiopharmaceuticals.

The SGK1 Kinase Inhibitor SI113 Sensitizes Theranostic Effects of the 64CuCl2 in Human Glioblastoma Multiforme Cells

“…Several positron-emitting radionuclides with a high atomic number and/ or a long half-life have been proposed both for imaging and therapeutic approach. Among these, Cu radioisotopes seem to be significantly interesting [1,4,11,12]. Cu radioisotopes, as a group, comprise radioisotopes which, due to their emission properties, may be applied both for diagnostic studies ( Cu) [13].…”

PAMAM Dendrimer‐Based Nanodevices for Nuclear Medicine Applications

“…As one of the most frequently used positron emitters, 64 Cu has a relatively long half‐life (t 1/2 = 12.7 h) and attractive decay characteristics (β+, 655 keV, 17.8%) . To apply 64 Cu for improved PET imaging of tumors, we recently explored the use of a multifunctional G5 PAMAM dendrimer nanoplatform modified with FA and fluorescein isothiocyante (FI) to radiolabel with 64 Cu via DOTA chelation 12b.…”

Positron emission tomography for measurement of copper fluxes in live organisms

“…Positron emission tomography (PET) scanners currently manufactured have higher sensitivity and much better spatial resolution compared to the nuclear scintillation cameras previously used for studying copper metabolism in humans . Multiple positron emitter copper radioisotopes, which include 60 Cu ( t 1/2 23.7 min, 93% β + , 7% EC), 61 Cu ( t 1/2 3.32 h, 60% β + , 40% EC), 62 Cu ( t 1/2 9.74 min; 98% β + , 2% EC), and 64 Cu ( t 1/2 12.7 h, 17.4% β + , 43% EC, 39% β − ), were evaluated for the preparation of PET radiopharmaceuticals . Among these copper radioisotopes, 64 Cu is particularly suitable for the measurement of whole‐body copper fluxes in view of its desirable t 1/2 time of 12.7 h, the feasible production of 64 Cu with a biomedical cyclotron, and the delivery of 64 Cu from the production site to a laboratory or imaging facility at a distant location.…”

“…[37][38][39] Multiple positron emitter copper radioisotopes, which include 60 Cu (t 1/2 23.7 min, 93% ␤ + , 7% EC), 61 Cu (t 1/2 3.32 h, 60% ␤ + , 40% EC), 62 Cu (t 1/2 9.74 min; 98% ␤ + , 2% EC), and 64 Cu (t 1/2 12.7 h, 17.4% ␤ + , 43% EC, 39% ␤ − ), were evaluated for the preparation of PET radiopharmaceuticals. [40][41][42][43][44] Among these copper radioisotopes, 64 Cu is particularly suitable for the measurement of whole-body copper fluxes in view of its desirable t 1/2 time of 12.7 h, the feasible production of 64 Cu with a biomedical cyclotron, 45 and the delivery of 64 Cu from the production site to a laboratory or imaging facility at a distant location. The introduction of a smallanimal PET scanner [46][47][48] revived research interest in preclinical investigation of inherited and acquired copper metabolism disorders using 64 Cu (Table 1).…”