Comparative analysis of positron emitters for theranostic applications based on small bioconjugates highlighting 43Sc, 61Cu and 45Ti

Abstract

BackgroundTargeted radionuclide therapy with 177Lu-labelled small conjugates is expanding rapidly, and its success is linked to appropriate patient selection. Companion diagnostic conjugates are usually labelled with 68Ga, offering good imaging up to ≈2 h post-injection. However, the optimal tumor-to-background ratio is often reached later. This study examined promising positron-emitting radiometals with half-lives between 3 h and 24 h and β+ intensity (Iβ+) ≥ 15% and compared them to 68Ga. The radiometals included: 43Sc, 44Sc, 45Ti, 55Co, 61Cu, 64Cu, 66Ga, 85mY, 86Y, 90Nb, 132La, 150Tb and 152Tb. 133La (7.2% Iβ+) was also examined because it was recently discussed, in combination with 132La, as a possible diagnostic match for 225Ac.MethodsTotal electron and photon doses per decay and per positron; possibly interfering γ-ray emissions; typical activities to be injected for same-day imaging; positron range; and available production routes were examined.ResultsFor each annihilation process useful for PET imaging, the total energy released (MeV) is: 45Ti (1.5), 43Sc (1.6), 61Cu and 64Cu (1.8), 68Ga (1.9), 44Sc and 133La (2.9), 55Co (3.2), 85mY (3.3), 132La (4.8), 152Tb (6.5), 150Tb (7.1), 90Nb (8.6), and 86Y (13.6). Significant amounts (≥ 10%) of ≈0.5 MeV photons that may fall into the acceptance window of PET scanners are emitted by 55Co, 66Ga, 85mY, 86Y, 132La, and 152Tb. Compton background from more energetic photons would be expected for 44Sc, 55Co, 66Ga, 86Y, 90Nb, 132La,150Tb, and 152Tb. The mean positron ranges (mm) of 64Cu (0.6), 85mY (1.0), 45Ti (1.5), 133La (1.6), 43Sc and 61Cu (1.7), 55Co (2.1), 44Sc and 86Y (2.5), and 90Nb (2.6) were lower than that of 68Ga (3.6). DOTA chelation is applicable for most of the radiometals, though not ideal for 61Cu/64Cu. Recent data showed that chelation of 45Ti with DOTA is feasible. 90Nb requires different complexing agents (e.g., DFO). Finally, they could be economically produced by proton-induced reactions at medical cyclotrons.ConclusionIn particular, 43Sc, 45Ti, and 61Cu have overall excellent β+ decay-characteristics for theranostic applications complementing 177Lu-labelled small conjugates, and they could be sustainably produced. Like Lu, 43Sc, 45Ti and to a lesser extent 61Cu could be labelled with DOTA.