Early Evaluation of Copper Radioisotope Production at ISOLPHARM

Abstract

The ISOLPHARM (ISOL technique for radioPHARMaceuticals) project is dedicated to the development of high purity radiopharmaceuticals exploiting the radionuclides producible with the future Selective Production of Exotic Species (SPES) Isotope Separation On-Line (ISOL) facility at the Legnaro National Laboratories of the Italian National Institute for Nuclear Physics (INFN-LNL). At SPES, a proton beam (up to 70 MeV) extracted from a cyclotron will directly impinge a primary target, where the produced isotopes are released thanks to the high working temperatures (2000 °C), ionized, extracted and accelerated, and finally, after mass separation, only the desired nuclei are collected on a secondary target, free from isotopic contaminants that decrease their specific activity. A case study for such project is the evaluation of the feasibility of the ISOL production of 64Cu and 67Cu using a zirconium germanide target, currently under development. The producible activities of 64Cu and 67Cu were calculated by means of the Monte Carlo code FLUKA, whereas dedicated off-line tests with stable beams were performed at LNL to evaluate the capability to ionize and recover isotopically pure copper.

Copper Coordination Chemistry of Sulfur Pendant Cyclen Derivatives: An Attempt to Hinder the Reductive-Induced Demetalation in 64/67Cu Radiopharmaceuticals

“… 4 − 6 Furthermore, 64 Cu can provide a matched PET imaging pair with the pure β – emitter copper-67 ( 67 Cu, t 1/2 61.9 h, β – 100%, E β – ,max 141 keV). 7 , 8 The theranostic approach of using both 64 Cu and 67 Cu can allow low-dose scouting scans to obtain dosimetry information, followed by higher dose therapy in the same patient, thus taking a major step toward personalized medicine. 9 …”

“…A flourished number of researches have been conducted during the past decades to develop radiopharmaceuticals for noninvasive imaging and treatment of tumors. In particular, copper has received much interest because it possesses several radioisotopes (copper-60, copper-61, copper-62, copper-64, and copper-67) with half-life and emission properties suitable for diagnostic and therapeutic applications. − Copper-64 ( 64 Cu, t 1/2 12.7 h) is undoubtedly the most versatile because its unique decay profile, which combines electron capture ( I EC 43%), β + ( I β + 18%, E β + ,max 655 keV) and β – emission ( I β – 39%, E β – ,max 573 keV), makes it suitable for positron emission tomography (PET) imaging and, in principle, radiotherapy by using the same radiopharmaceutical. − Furthermore, 64 Cu can provide a matched PET imaging pair with the pure β – emitter copper-67 ( 67 Cu, t 1/2 61.9 h, β – 100%, E β – ,max 141 keV). , The theranostic approach of using both 64 Cu and 67 Cu can allow low-dose scouting scans to obtain dosimetry information, followed by higher dose therapy in the same patient, thus taking a major step toward personalized medicine …”

“…4−6 Furthermore, 64 Cu can provide a matched PET imaging pair with the pure β − emitter copper-67 ( 67 Cu, t 1/2 61.9 h, β − 100%, E β − ,max 141 keV). 7,8 The theranostic approach of using both 64 Cu and 67 Cu can allow low-dose scouting scans to obtain dosimetry information, followed by higher dose therapy in the same patient, thus taking a major step toward personalized medicine. 9 To obtain site-specific delivery of the emitted radiation, the radioisotopes must be firmly coordinated by a bifunctional chelator (BFC) appended to a tumor-targeting biomolecule (e.g., small molecule, peptide, or antibody) through a covalent linkage.…”

Chelation of Theranostic Copper Radioisotopes with S-Rich Macrocycles: From Radiolabelling of Copper-64 to In Vivo Investigation

“…In particular, copper-64 (t 1/2 = 12.7 h) possesses a rare emission profile which combines β + (E β + , max = 655 keV, I β + = 18%), β − (E β − , max = 573 keV, I β − = 39%,) and electron capture emissions (I EC = 43%). The relatively low β + -energy is comparable to that of fluorine-18, and the resulting annihilation photons produce high-quality images [11][12][13][14][15][16]. Moreover, its relatively long half-life can enable positron emission tomography (PET) imaging at later time points than for fluorine-18.…”

“…Although its decay profile would make copper-64 a dual diagnostic and therapeutic radionuclide, the high positron branching ratio precludes the latter use [11]. However, copper-64 retains the potential for theranostic applications when paired with the pure β − emitter copper-67 (t 1/2 = 61.9 h, E β − , max = 141 keV, I β − = 100%) [12][13][14][15].…”