TY - JOUR
T1 - 66Ga
T2 - A Novelty or a Valuable Preclinical Screening Tool for the Design of Targeted Radiopharmaceuticals?
AU - Amor-Coarasa, Alejandro
AU - Kelly, James M.
AU - Ponnala, Shashikanth
AU - Nikolopoulou, Anastasia
AU - Williams, Clarence
AU - Babich, John W.
N1 - Funding Information:
Funding: This research was funded in part by an NIH Ruth L. Kirschstein National Research Service Award (Grant Number: F32CA203473, recipient: Alejandro Amor-Coarasa).
Publisher Copyright:
© 2018 MDPI AG. All rights reserved.
PY - 2018/10/9
Y1 - 2018/10/9
N2 - Emerging interest in extending the plasma half-life of small molecule radioligands warrants a consideration of the appropriate radionuclide for PET imaging at longer time points (>8 h). Among candidate positron-emitting radionuclides, 66Ga (t1/2 = 9.5 h,β+ = 57%) has suitable nuclear and chemical properties for the labeling and PET imaging of radioligands of this profile. We investigated the value of 66Ga to preclinical screening and the evaluation of albumin-binding PSMA-targeting small molecules. 66Ga was produced by irradiation of a natZn target. 66Ga3+ ions were separated from Zn2+ ions by an optimized UTEVA anion exchange column that retained 99.99987% of Zn2+ ions and allowed 90.2 ± 2.8% recovery of 66Ga3+. Three ligands were radiolabeled in 46.4 ± 20.5%; radiochemical yield and >90% radiochemical purity. Molar activity was 632 ± 380 MBq/mol. Uptake in the tumor and kidneys at 1, 3, 6, and 24 h p.i. was determined by μPET/CT imaging and more completely predicted the distribution kinetics than uptake of the [66Ga]Ga-labeled ligands did. Although there are multiple challenges to the use of 66Ga for clinical PET imaging, it can be a valuable research tool for ligand screening and preclinical imaging beyond 24 h.
AB - Emerging interest in extending the plasma half-life of small molecule radioligands warrants a consideration of the appropriate radionuclide for PET imaging at longer time points (>8 h). Among candidate positron-emitting radionuclides, 66Ga (t1/2 = 9.5 h,β+ = 57%) has suitable nuclear and chemical properties for the labeling and PET imaging of radioligands of this profile. We investigated the value of 66Ga to preclinical screening and the evaluation of albumin-binding PSMA-targeting small molecules. 66Ga was produced by irradiation of a natZn target. 66Ga3+ ions were separated from Zn2+ ions by an optimized UTEVA anion exchange column that retained 99.99987% of Zn2+ ions and allowed 90.2 ± 2.8% recovery of 66Ga3+. Three ligands were radiolabeled in 46.4 ± 20.5%; radiochemical yield and >90% radiochemical purity. Molar activity was 632 ± 380 MBq/mol. Uptake in the tumor and kidneys at 1, 3, 6, and 24 h p.i. was determined by μPET/CT imaging and more completely predicted the distribution kinetics than uptake of the [66Ga]Ga-labeled ligands did. Although there are multiple challenges to the use of 66Ga for clinical PET imaging, it can be a valuable research tool for ligand screening and preclinical imaging beyond 24 h.
KW - Ga
KW - PET imaging
KW - Preclinical screening
KW - Targeted radiotherapy
UR - http://www.scopus.com/inward/record.url?scp=85054787892&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85054787892&partnerID=8YFLogxK
U2 - 10.3390/molecules23102575
DO - 10.3390/molecules23102575
M3 - Article
C2 - 30304795
AN - SCOPUS:85054787892
SN - 1420-3049
VL - 23
JO - Molecules
JF - Molecules
IS - 10
M1 - 2575
ER -