Synthesis of DOTA-pyridine chelates for 64Cu coordination and radiolabeling of ?MSH peptide

Abstract Background 64 Cu is one of the few radioisotopes that can be used for both imaging and therapy, enabling theranostics with identical chemical composition. Development stable chelators essential to harness potential this isotope, challenged by presence endogenous copper chelators. Pyridyl type show good coordination ability copper, prompting present study a series chelates DOTA-xPy (x = 1–4) sequentially substitute carboxyl moieties pyridyl on DOTA backbone. Results We found groups significantly increases labeling conversion yield, DOTA-2Py, ?3Py -4Py quantitatively complexing at room temperature within 5 min (1 × 10 ? 4 M). [ Cu]Cu-DOTA-xPy 2–4) exhibited stability in human serum up 24 h. When 1000 eq. NOTA, no transmetallation was observed all three complexes. 1–3) were conjugated cyclized ?-melanocyte-stimulating hormone (?MSH) peptide using pendant as bifunctional handle. Cu]Cu-DOTA-xPy-?MSH retained (> 96% h) showed high binding affinity (Ki 2.1–3.7 nM) towards melanocortin 1 receptor. Conclusion are promising Cu. Further vivo evaluation necessary assess full these tool enable further theranostic radiopharmaceutical development.