title: 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.
authors: Isotope Applications & Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai, 400085, India.
authors: Akanksha
authors: A
authors: Jindal
authors: Anupam
authors: A
authors: Mathur
authors: Usha
authors: U
authors: Pandey
authors: H D
authors: HD
authors: Sarma
authors: Pradip
authors: P
authors: Chaudhari
authors: Ashutosh
authors: A
authors: Dash
mesh_terms: D000818:Animals; D005227:Fatty Acids / Q000737:chemistry / Q000493:pharmacokinetics*; D005710:Gallium Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics*; D006321:Heart / Q000000981:diagnostic imaging*; D006571:Heterocyclic Compounds / Q000737:chemistry / Q000493:pharmacokinetics; D006573:Heterocyclic Compounds, 1-Ring; D008657:Metabolic Clearance Rate; D051379:Mice; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D005227:Fatty Acids; D005710:Gallium Radioisotopes; D006571:Heterocyclic Compounds; D006573:Heterocyclic Compounds, 1-Ring; D019275:Radiopharmaceuticals; C048993:1,4,7-triazacyclononane-N,N',N''-triacetic acid
keywords: 68Ga; [11C]palmitate; fatty acid labeling; metabolic cardiac imaging