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This Article Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Ferreira, C. Articles by Jurek, P. PubMed Articles by Ferreira, C. Articles by Jurek, P.

Evaluating bifunctional chelates for metal radioisotopes

¹ MDS Nordion, Vancouver, British Columbia, Canada; ² BC Cancer Agency, Vancouver, British Columbia, Canada; ³ Macrocyclics, Dallas, Texas

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Objectives: Numerous metal radioisotopes are attractive for diagnostic and/or therapeutic applications. To attach a metal radioisotope to a targeting molecule a bifunctional chelate (BFC) is typically required. Currently available BFCs are limited by either their radiolabeling chemistry or physiological stability. With the goal of identifying highly effective BFCs, we compared the properties of the widely used DOTA with two novel BFCs containing the macrocyclic chelating moieties 1-oxa-4,7,10-triazacyclododecane-4,7,10-triacetic acid (Oxo) and 3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene-3,5,9-triacetic acid (PCTA).

Methods: DOTA, Oxo and PCTA were each radiolabeled with Cu-64, Ga-67, In-111, and Y-90. BFC concentration, activity concentration and pH were all varied to assess the robustness of the radiolabeling. Stability of each BFC radioisotope pair was evaluated at low pH and in serum. Imaging and biodistribution studies in mice were completed with the Cu-64 radiolabeled BFCs.

Results: Oxo and PCTA possessed superior reaction kinetics compared to DOTA under all radiolabeling conditions. For In-111 and Cu-64, >98% radiochemical yields were achieved in <5 min at room temperature even when using stoichiometric amounts of BFC. Oxo and PCTA were efficiently labeled at a pH as low as 2 and as high as 9. Improved stability in serum and at pH 2 was also observed. The imaging and biodistribution of the Cu-64 radiolabeled BFCs illustrated differences between the chelates, including preferential clearance via the kidneys for PCTA.

Conclusions: Oxo and PCTA facilitate efficient radiolabeling under mild conditions to produce stable complexes at potentially high specific activities with all radioisotopes investigated. These BFCs may find wide utility in the development of metal based radiopharmaceuticals.

This Article Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Ferreira, C. Articles by Jurek, P. PubMed Articles by Ferreira, C. Articles by Jurek, P.