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

基于小型生物偶联物的正电子发射体在诊疗应用中的比较分析,重点关注(43)Sc、(61)Cu和(45)Ti。

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Abstract

BACKGROUND: Targeted radionuclide therapy with (177)Lu-labelled small conjugates is expanding rapidly, and its success is linked to appropriate patient selection. Companion diagnostic conjugates are usually labelled with (68)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(β+)) ≥ 15% and compared them to (68)Ga. The radiometals included: (43)Sc, (44)Sc, (45)Ti, (55)Co, (61)Cu, (64)Cu, (66)Ga, (85m)Y, (86)Y, (90)Nb, (132)La, (150)Tb and (152)Tb. (133)La (7.2% I(β+)) was also examined because it was recently discussed, in combination with (132)La, as a possible diagnostic match for (225)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: (45)Ti (1.5), (43)Sc (1.6), (61)Cu and (64)Cu (1.8), (68)Ga (1.9), (44)Sc and (133)La (2.9), (55)Co (3.2), (85m)Y (3.3), (132)La (4.8), (152)Tb (6.5), (150)Tb (7.1), (90)Nb (8.6), and (86)Y (13.6). Significant amounts (≥ 10%) of ≈0.5 MeV photons that may fall into the acceptance window of PET scanners are emitted by (55)Co, (66)Ga, (85m)Y, (86)Y, (132)La, and (152)Tb. Compton background from more energetic photons would be expected for (44)Sc, (55)Co, (66)Ga, (86)Y, (90)Nb, (132)La,(150)Tb, and (152)Tb. The mean positron ranges (mm) of (64)Cu (0.6), (85m)Y (1.0), (45)Ti (1.5), (133)La (1.6), (43)Sc and (61)Cu (1.7), (55)Co (2.1), (44)Sc and (86)Y (2.5), and (90)Nb (2.6) were lower than that of (68)Ga (3.6). DOTA chelation is applicable for most of the radiometals, though not ideal for (61)Cu/(64)Cu. Recent data showed that chelation of (45)Ti with DOTA is feasible. (90)Nb requires different complexing agents (e.g., DFO). Finally, they could be economically produced by proton-induced reactions at medical cyclotrons. CONCLUSION: In particular, (43)Sc, (45)Ti, and (61)Cu have overall excellent β(+) decay-characteristics for theranostic applications complementing (177)Lu-labelled small conjugates, and they could be sustainably produced. Like Lu, (43)Sc, (45)Ti and to a lesser extent (61)Cu could be labelled with DOTA.

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