TY - JOUR
T1 - 67Ga-metalloprobes
T2 - monitoring the impact of geometrical isomers on accumulation profiles in rat cardiomyoblasts and human breast carcinoma cells
AU - Sivapackiam, Jothilingam
AU - Harpstrite, Scott E.
AU - Rath, Nigam P.
AU - Sharma, Vijay
N1 - Funding Information:
The authors thank Prof. David Piwnica-Worms (MD Anderson, University of Texas, Houston, TX) for helpful discussions. Financial assistance to this work was provided by grants from NIH grants RO1 HL111163 (VS) and R33 AG033328 (VS).
Publisher Copyright:
© The Royal Society of Chemistry.
PY - 2017
Y1 - 2017
N2 - Geometrically similar monocationic gallium(iii) complexes and their radiolabeled SPECT counterparts were obtained from Schiff base precursor ligands using ligand exchange reactions to evaluate the impact of cis and trans-isomers on their cellular accumulation profiles in rat cardiomyoblasts (H9c2(2-1)) and human breast carcinoma (MCF-7neo) cells. 67Ga-metalloprobes comprising trans-phenolates showing an overall octahedral geometry and exhibiting uniform spatial distribution of positive charges on their molecular surface show steady-state accumulation in H9c2(2-1) and MCF-7neo cells, and localize in the mitochondria of the cells. Importantly, the surrogate geometrically similar and monocationic metalloprobe counterparts possessing the cis arrangement of phenolates do not show cellular uptake in H9c2(2-1) and MCF-7neo cells. Exploiting their modest fluorescent traits, live cell imaging indicates that trans-isomers of metalloprobes localize within the mitochondria of cells following their penetration, thereby indicating the excellent correlation of radiotracer data and live-cell microscopy results. Overall, these results indicate that the cell uptake profiles of metalloprobes within this class are mediated by the spatial distribution of charges over their molecular surface and hydrophobicity.
AB - Geometrically similar monocationic gallium(iii) complexes and their radiolabeled SPECT counterparts were obtained from Schiff base precursor ligands using ligand exchange reactions to evaluate the impact of cis and trans-isomers on their cellular accumulation profiles in rat cardiomyoblasts (H9c2(2-1)) and human breast carcinoma (MCF-7neo) cells. 67Ga-metalloprobes comprising trans-phenolates showing an overall octahedral geometry and exhibiting uniform spatial distribution of positive charges on their molecular surface show steady-state accumulation in H9c2(2-1) and MCF-7neo cells, and localize in the mitochondria of the cells. Importantly, the surrogate geometrically similar and monocationic metalloprobe counterparts possessing the cis arrangement of phenolates do not show cellular uptake in H9c2(2-1) and MCF-7neo cells. Exploiting their modest fluorescent traits, live cell imaging indicates that trans-isomers of metalloprobes localize within the mitochondria of cells following their penetration, thereby indicating the excellent correlation of radiotracer data and live-cell microscopy results. Overall, these results indicate that the cell uptake profiles of metalloprobes within this class are mediated by the spatial distribution of charges over their molecular surface and hydrophobicity.
UR - http://www.scopus.com/inward/record.url?scp=85010711791&partnerID=8YFLogxK
U2 - 10.1039/c6md00474a
DO - 10.1039/c6md00474a
M3 - Article
C2 - 30108701
AN - SCOPUS:85010711791
SN - 2040-2503
VL - 8
SP - 158
EP - 161
JO - MedChemComm
JF - MedChemComm
IS - 1
ER -