Development of ⁶⁸Ga‐labeled fatty acids for their potential use in cardiac metabolic imaging

Abstract

While [(11)C]palmitate continues to be a promising tracer for cardiovascular Positron Emission Tomography (PET) imaging, unfavourable logistics due to the short half-life of (11)C (20 min) and cumbersome labeling methodologies are the major impediments that limit its widespread use. In order to circumvent such limitations, an attempt has been made to explore the potential of (68)Ga-labeled fatty acid analogs for metabolic imaging owing to the availability of (68)Ga through a (68)Ge/(68)Ga generator on an on-demand basis. In this study, two fatty acid conjugates were synthesized by conjugation of p-SCN-benzyl NOTA with the ω-amino group of 11-amino undecanoic acid and 12-amino dodecanoic acid, respectively, under alkaline conditions. Both derivatives were radiolabeled in high yields with (68)Ga obtained from an in-house (68)Ge/(68)Ga generator. Biodistribution studies in Swiss mice showed reasonable myocardial uptake at 2 min for both derivatives (7.4 ± 2.8% ID/g for 11-carbon fatty acid-NOTA conjugate and 6.4 ± 2.1% ID/g for 12-carbon fatty acid-NOTA conjugate), which cleared rapidly over 30 min. However, significant activity was found in blood for both tracers, with heart/blood ratios observed to be below 0.5 at all time points, diminishing the potential of the synthesized complexes for cardiac imaging.

Emerging Tracers for Nuclear Cardiac PET Imaging

“…Thus, the 68 Ge/ 68 Ga generator is appropriate for experimental or clinical application [58]. Many kinds of synthetic complexes of 68 Ga(III) have been reported as candidate PET tracers for cardiac nuclear imaging [58][59][60][61][62][63][64][65][66][67][68][69][70][71]. In this review, we have categorized them according to their characteristics, as perfusion imaging agents, MI imaging agents and cardiac metabolic imaging agents, and we have summarized them (Table 3).…”

“…Thus, radioisotope-labeled long-chain fatty acids have been investigated as imaging agents since the 1990s [78,79]. Finally, several kinds of 68 Ga-labeled longchain fatty acids were synthesized and evaluated [70,71]. The first reported 68 Ga-labeled fatty acids were 68 Ga-NOTAundecanoic acid and 68 Ga-NOTA-dodecanoic acid [70].…”

“…Finally, several kinds of 68 Ga-labeled longchain fatty acids were synthesized and evaluated [70,71]. The first reported 68 Ga-labeled fatty acids were 68 Ga-NOTAundecanoic acid and 68 Ga-NOTA-dodecanoic acid [70]. These radiotracers showed significant initial uptake in the myocardium; however, significant retention of the activity was found to be associated with blood.…”

Bifunctional Gallium-68 Chelators: Past, Present, and Future

“…There are many publications with several target vectors. 113,118,127,136,143,[149][150][151][152][153][154][155][156][157] A really new and promising TACN derivate is TRAP (3,3 0 ,3″- (((1,4,7-triazonane-1,4,7-triyl)tris(methylene))tris(hydroxyphosphoryl))tripropanoic acid). It has been mentioned 2010 by Notni et al 120 and many articles have been published about this topic during the past 5 years.…”

Imaging of intracellular fatty acids by scanning X‐ray fluorescence microscopy

“…All reagents and solvents were purchased commercially and used as received. 1 H nuclear magnetic resonance (NMR) and 13 C NMR spectra were recorded on a spectrometer (AL-400; Jeol, Akishima, Japan) using CDCl 3 as the solvent and tetramethylsilane as an internal standard. Multiplicities are indicated as br (broadened), s (singlet), d (doublet), t (triplet), q (quartet), and m (multiplet).…”