Production, purification and radiolabeling of radiometals produced in a liquid target on a 13 MeV medical cyclotron

Objectives Radiometals for PET imaging are typically produced via solid target irradiation on cyclotrons or obtained from generators. We present here a simple method for the production of research quantities of various radiometals using a modified liquid-target system. Our goal is to expand availability of these radiometals and enable isotope-biomolecule optimization studies for preclinical development of radiopharmaceuticals with unknown pharmacokinetic profiles.

Methods Salt solutions of natural isotopic abundance were irradiated in a standard water target on our 13 MeV cyclotron for 60 min. After irradiation, all solutions were withdrawn from the target and purified using cation exchange or chelating resins. The methods were modified and optimized if required due to the high concentration of the salt solutions. Target solutions and the final eluate were characterized by gamma spectroscopy and by ICP-MS prior to radiolabeling experiments with commercially available chelates.

Results Several isotopes (68Ga, 61Cu, 89Zr, 44Sc [1], 89Y, 94mTc [2]) were produced in a standard water target on our 13 MeV cyclotron (see Table 1), fully characterized and radiolabeled successfully.

Conclusions We have utilized a liquid target system to produce research quantities of several radiometallic isotopes. With the exception of 86Y, this approach is a viable route to obtain sufficient quantities for pre-clinical testing. Preliminary tests with a new target design [3] have shown that it is possible to put a proton beam of 20 μA on target. Using Ca(NO3)2, we were able to produce 28 ± 1 MBq of 44Sc at end of bombardement (EOB) in 60 min (n = 2). Future work will explore this target design for all isotopes discussed, with the expectation to achieve even higher production yields than those reported here.

Research Support The authors wish to thank the Canadian Institute for Health Research - Collaborative Health Research Project (CIHR-CHRP) for funding.