title: 68Ga labeled fatty acids for cardiac metabolic imaging: Influence of different bifunctional chelators.
abstract: Development of68Ga labeled fatty acids is of immense interest due to the availability of68Ga through a generator and its superiority over SPECT based tracers in carrying out dynamic imaging on a PET scanner. Our present work explores the influence of different chelators on the cardiac uptake and pharmacokinetics of the68Ga-labeled fatty acids. Two new68Ga labeled fatty acids were synthesized by conjugation of 11-aminoundecanoic acid with the bifunctional chelators (BFCs) viz. p-SCN-Bn-DTPA (S-2-(4-isothiocyanatobenzyl)-diethylenetriaminepentaacetic acid) and p-SCN-Bn-NODAGA (S-2-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1-glutaric acid-4,7-acetic acid) and their comparison was carried out with the previously reported68Ga-NOTA-undecanoic acid. Both the conjugates were radiolabeled with68Ga in high yields and purities (>95%). Their formation was established by preparation and characterization of their inactive analogs withnatGa at macroscopic levels. Biodistribution studies of the complexes in Swiss mice showed lower initial myocardial uptake for68Ga-NODAGA-undecanoic acid (3.8±0.6%ID/g) and68Ga-DTPA-undecanoic acid (1.3±0.5%ID/g) complexes in comparison to previously reported68Ga-NOTA-undecanoic acid complex (7.4±2.8%ID/g) at 2min p.i. However, significant retention of the tracer in the myocardium was observed in the case of68Ga-NODAGA-undecanoic complex, which led to improved heart/non-target ratios of the complex over time in comparison to the other68Ga complexes. Similarly, the DTPA complex exhibited increased washout from the liver in comparison to other68Ga derivatives. The β oxidation mechanism in myocytes was investigated by isolating the myocardial extract post intravenous injection of the respective68Ga complexes and analyzing them by radio-HPLC, which showed metabolic transformation of the parent fatty acid complex peak in all the three complexes. This study has provided an insight into the design characteristics of68Ga labeled fatty acids to achieve the desired myocardial imaging characteristics.
authors: Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085, India.
authors: Akanksha
authors: A
authors: Jain
authors: Radiopharmaceuticals Program, Board of Radiation and Isotope Technology, Navi Mumbai 400 703, India.
authors: Anupam
authors: A
authors: Mathur
authors: Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085, India.
authors: Usha
authors: U
authors: Pandey
authors: Radiation Biology & Health Sciences Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085, India.
authors: Haladhar Dev
authors: HD
authors: Sarma
authors: Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085, India. Electronic address: adash@barc.gov.in.
authors: Ashutosh
authors: A
authors: Dash
mesh_terms: D000085:Acetates / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D005227:Fatty Acids / Q000737:chemistry* / Q000493:pharmacokinetics*; D005710:Gallium Radioisotopes / Q000737:chemistry* / Q000493:pharmacokinetics*; D006571:Heterocyclic Compounds / Q000737:chemistry / Q000493:pharmacokinetics; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry / Q000493:pharmacokinetics; D051379:Mice; D009206:Myocardium / Q000378:metabolism*; D004369:Pentetic Acid / Q000737:chemistry / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography; D014018:Tissue Distribution
chemical_list: C572723:1-(1,3-carboxypropyl)-4,7-carboxymethyl-1,4,7-triazacyclononane; D000085:Acetates; D005227:Fatty Acids; D005710:Gallium Radioisotopes; D006571:Heterocyclic Compounds; D006573:Heterocyclic Compounds, 1-Ring; C016173:undecanoic acid; C048993:1,4,7-triazacyclononane-N,N',N''-triacetic acid; D004369:Pentetic Acid
keywords: DTPA; Fatty acids; Ga-68; Heart metabolite analysis; NODAGA; NOTA