Comparative analysis of positron emitters for theranostic applications based on small bioconjugates highlighting...

Targeted 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 (I_β+) ≥ 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% I_β+) was also examined because it was recently discussed, in combination with ¹³²La, as a possible diagnostic match for ²²⁵Ac.

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.

For 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.

In 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.