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

BACKGROUND

Targeted radionuclide therapy with Lu-labelled small conjugates is expanding rapidly, and its success is linked to appropriate patient selection. Companion diagnostic conjugates are usually labelled with Ga, 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 (I) ≥ 15% and compared them to Ga. The radiometals included: Sc, Sc, Ti, Co, Cu, Cu, Ga, Y, Y, Nb, La, Tb and Tb. La (7.2% I) was also examined because it was recently discussed, in combination with La, as a possible diagnostic match for Ac.

METHODS

Total 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.

RESULTS

For each annihilation process useful for PET imaging, the total energy released (MeV) is: Ti (1.5), Sc (1.6), Cu and Cu (1.8), Ga (1.9), Sc and La (2.9), Co (3.2), Y (3.3), La (4.8), Tb (6.5), Tb (7.1), Nb (8.6), and Y (13.6). Significant amounts (≥ 10%) of ≈0.5 MeV photons that may fall into the acceptance window of PET scanners are emitted by Co, Ga, Y, Y, La, and Tb. Compton background from more energetic photons would be expected for Sc, Co, Ga, Y, Nb, La,Tb, and Tb. The mean positron ranges (mm) of Cu (0.6), Y (1.0), Ti (1.5), La (1.6), Sc and Cu (1.7), Co (2.1), Sc and Y (2.5), and Nb (2.6) were lower than that of Ga (3.6). DOTA chelation is applicable for most of the radiometals, though not ideal for Cu/Cu. Recent data showed that chelation of Ti with DOTA is feasible. Nb requires different complexing agents (e.g., DFO). Finally, they could be economically produced by proton-induced reactions at medical cyclotrons.

CONCLUSION

In particular, Sc, Ti, and Cu have overall excellent β decay-characteristics for theranostic applications complementing Lu-labelled small conjugates, and they could be sustainably produced. Like Lu, Sc, Ti and to a lesser extent Cu could be labelled with DOTA.