Loading…
Improving the In Vivo Stability of 52MnMn(II) Complexes with 18-Membered Macrocyclic Chelators for PET Imaging
We report the [natMn/52Mn]Mn(II) complexes of the macrocyclic chelators PYAN [3,6,10,13-tetraaza-1,8(2,6)-dipyridinacyclotetradecaphane] and CHXPYAN [(41R,42R,101R,102R)-3,5,9,11-tetraaza-1,7(2,6)-dipyridina-4,10(1,2)-dicyclohexanacyclododecaphane]. The X-ray crystal structures of Mn-PYAN and Mn-CHX...
Saved in:
Published in: | Journal of medicinal chemistry 2024-07, Vol.67 (13), p.11242 |
---|---|
Main Authors: | , , , , , , , , , |
Format: | Article |
Language: | English |
Online Access: | Get full text |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
Summary: | We report the [natMn/52Mn]Mn(II) complexes of the macrocyclic chelators PYAN [3,6,10,13-tetraaza-1,8(2,6)-dipyridinacyclotetradecaphane] and CHXPYAN [(41R,42R,101R,102R)-3,5,9,11-tetraaza-1,7(2,6)-dipyridina-4,10(1,2)-dicyclohexanacyclododecaphane]. The X-ray crystal structures of Mn-PYAN and Mn-CHXPYAN evidence distorted octahedral geometries through coordination of the nitrogen atoms of the macrocycles. Cyclic voltammetry studies evidence reversible processes due to the Mn(II)/Mn(III) pair, indicating that the complexes are resistant to oxidation. CHXPYAN forms a more thermodynamically stable and kinetically inert Mn(II) complex than PYAN. Radiochemical studies with the radioactive isotope manganese-52 (52Mn, t1/2 = 5.6 days) evidenced better radiochemical yields for CHXPYAN than for PYAN. Both [52Mn]Mn(II) complexes remained stable in mouse and human serum, so in vivo stability studies were carried out. Positron emission tomography/computed tomography scans and biodistribution assays indicated that [52Mn]Mn-PYAN has a distribution pattern similar to that of [52Mn]MnCl2, showing persistent radioactivity accumulation in the kidneys. Conversely, [52Mn]Mn-CHXPYAN remained stable in vivo, clearing quickly from the liver and kidneys.We report the [natMn/52Mn]Mn(II) complexes of the macrocyclic chelators PYAN [3,6,10,13-tetraaza-1,8(2,6)-dipyridinacyclotetradecaphane] and CHXPYAN [(41R,42R,101R,102R)-3,5,9,11-tetraaza-1,7(2,6)-dipyridina-4,10(1,2)-dicyclohexanacyclododecaphane]. The X-ray crystal structures of Mn-PYAN and Mn-CHXPYAN evidence distorted octahedral geometries through coordination of the nitrogen atoms of the macrocycles. Cyclic voltammetry studies evidence reversible processes due to the Mn(II)/Mn(III) pair, indicating that the complexes are resistant to oxidation. CHXPYAN forms a more thermodynamically stable and kinetically inert Mn(II) complex than PYAN. Radiochemical studies with the radioactive isotope manganese-52 (52Mn, t1/2 = 5.6 days) evidenced better radiochemical yields for CHXPYAN than for PYAN. Both [52Mn]Mn(II) complexes remained stable in mouse and human serum, so in vivo stability studies were carried out. Positron emission tomography/computed tomography scans and biodistribution assays indicated that [52Mn]Mn-PYAN has a distribution pattern similar to that of [52Mn]MnCl2, showing persistent radioactivity accumulation in the kidneys. Conversely, [52Mn]Mn-CHXPYAN remained stable in vivo, clearing quickly from the liver and kidneys. |
---|---|
ISSN: | 1520-4804 1520-4804 |
DOI: | 10.1021/acs.jmedchem.4c00812 |