Imaging and dosimetric characteristics of ⁶⁷ Cu

Abstract

In recent years the use of beta-emitting radiopharmaceuticals for cancer therapy has expanded rapidly following development of therapeutics for neuroendocrine tumors, prostate cancer, and other oncologic malignancies. One emerging beta-emitting radioisotope of interest for therapy is 67Cu (t1/2: 2.6 d) due to its chemical equivalency with the widely-established positron-emitting isotope 64Cu (t1/2: 12.7 h). In this work we evaluate both the imaging and dosimetric characteristics of 67Cu, as well as producing the first report of SPECT/CT imaging using 67Cu. To this end, 67Cu was produced by photon-induced reactions on isotopically-enriched 68Zn at the Low-Energy Accelerator Facility (LEAF) of Argonne National Laboratory, followed by bulk separation of metallic 68Zn by sublimation and radiochemical purification by column chromatography. Gamma spectrometry was performed by efficiency-calibrated high-purity germanium (HPGe) analysis to verify absolute activity calibration and establish radionuclidic purity. Absolute activity measurements corroborated manufacturer-recommended dose-calibrator settings and no radionuclidic impurities were observed. Using the Clinical Trials Network anthropomorphic chest phantom, SPECT/CT images were acquired. Medium energy (ME) SPECT collimation was found to provide the best image quality from the primary 185 keV gamma emission of 67Cu. Reconstructed images of 67Cu were similar in quality to images acquired using 177Lu. Recovery coefficients were calculated and compared against quantitative images of 99mTc, 177Lu, and 64Cu within the same anthropomorphic chest phantom. Production and clinical imaging of 67Cu appears feasible, and future studies investigating the therapeutic efficacy of 67Cu-based radiopharmaceuticals are warranted.

67Cu Production Capabilities: A Mini Review

“…The photonuclear production for 67 Cu using bremsstrahlung photons with an e-LINAC accelerator has been studied for decades [ 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ]. Recently, a large enriched 68 Zn target (55.5 g) was irradiated with 40 MeV e-LINAC for 53.5 h, obtaining 62.9 GBq (1.7 Ci) without detecting 64 Cu [ 10 ]. The threshold energy of the 68 Zn(γ,x) 64 Cu reaction is E THR = 27.6 MeV [ 37 ].…”

“…For the production of 67 Cu via the 64 Ni(α,p) 67 Cu nuclear reaction, Ohya et al, used enriched 64 Ni target material ( 64 Ni 99.07%) [ 50 ]. Sublimation and the casting process have also been used to produce massive zinc ingot targets (50–100 g) for photonuclear production [ 10 , 31 ].…”

“…The use of γ-emissions of 67 Cu at 184.6 keV (48.7%) and rarely 93.3 keV (16.1%) for SPECT imaging, assuming that the branching ratios of 67 Cu’s γ-emissions are much higher than those of 177 Lu, is expected to provide higher imaging sensitivity [ 107 , 108 ]. It is relevant to underline the recent work on SPECT imaging with Derenzo phantom, to study SPECT image quality using 67 Cu [ 10 ]. The use of a medium energy (ME) collimator is typically recommended for 177 Lu, since its γ-ray has an energy of 208 keV, while for the 140 keV γ-ray emitted by 99m Tc, the gold-standard radionuclide for SPECT imaging, the low-energy high-resolution (LEHR) collimator is recommended.…”

“…While the production techniques for 64 Cu are well known and are usually based on the 64 Ni(p,n) 64 Cu, and 64 Ni(d,2n) 64 Cu reactions [ 9 ], the use of 67 Cu has been prevented by a lack of regular availability of sufficient quantities for preclinical and clinical studies. Only recently has 67 Cu become available in the U.S. through the Department of Energy Isotope Program (DOE-IP), in quantities and purities that are sufficient for medical research applications [ 10 ]. The investigation of 67 Cu supply worldwide is, therefore, a crucial point, and this review presents the state-of-art in 67 Cu production and medical applications.…”

Production scheme for diagnostic-therapeutic radioisotopes by accelerator neutrons

“…Note that recently high-quality 67 Cu has been produced by the 68 Zn(.,p) 67 Cu reaction at Argonne National Laboratory. 50) Concerning the 64 Cu and 67 Cu productions using accelerator neutrons, the main drawback comes from the low neutron flux, but not from the nuclear reaction processes, such as the cross section of a required RI or the high production yield of an impurity RI. As mentioned above a high neutron flux of 910 15 n/s at an average neutron energy of E n : 14 MeV can be obtained owing to recent progress in accelerator technology.…”