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- Title
Chelation of Theranostic Copper Radioisotopes with S-Rich Macrocycles: From Radiolabelling of Copper-64 to In Vivo Investigation.
- Authors
Tosato, Marianna; Verona, Marco; Favaretto, Chiara; Pometti, Marco; Zanoni, Giordano; Scopelliti, Fabrizio; Cammarata, Francesco Paolo; Morselli, Luca; Talip, Zeynep; van der Meulen, Nicholas P.; Di Marco, Valerio; Asti, Mattia
- Abstract
Copper radioisotopes are generally employed for cancer imaging and therapy when firmly coordinated via a chelating agent coupled to a tumor-seeking vector. However, the biologically triggered Cu2+-Cu+ redox switching may constrain the in vivo integrity of the resulting complex, leading to demetallation processes. This unsought pathway is expected to be hindered by chelators bearing N, O, and S donors which appropriately complements the borderline-hard and soft nature of Cu2+ and Cu+. In this work, the labelling performances of a series of S-rich polyazamacrocyclic chelators with [64Cu]Cu2+ and the stability of the [64Cu]Cu-complexes thereof were evaluated. Among the chelators considered, the best results were obtained with 1,7-bis [2-(methylsulfanyl)ethyl]-4,10,diacetic acid-1,4,7,10-tetraazacyclododecane (DO2A2S). DO2A2S was labelled at high molar activities in mild reaction conditions, and its [64Cu]Cu2+ complex showed excellent integrity in human serum over 24 h. Biodistribution studies in BALB/c nude mice performed with [64Cu][Cu(DO2A2S)] revealed a behavior similar to other [64Cu]Cu-labelled cyclen derivatives characterized by high liver and kidney uptake, which could either be ascribed to transchelation phenomena or metabolic processing of the intact complex.
- Subjects
RADIOLABELING; RADIOISOTOPES; CHELATION; COPPER; CHELATING agents; CANCER treatment
- Publication
Molecules, 2022, Vol 27, Issue 13, p4158
- ISSN
1420-3049
- Publication type
Article
- DOI
10.3390/molecules27134158