Ga labeled fatty acids for cardiac metabolic imaging: Influence of different bifunctional chelators.

Development of Ga labeled fatty acids is of immense interest due to the availability of Ga 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 the Ga-labeled fatty acids. Two new Ga 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 reported Ga-NOTA-undecanoic acid. Both the conjugates were radiolabeled with Ga in high yields and purities (>95%). Their formation was established by preparation and characterization of their inactive analogs with Ga at macroscopic levels. Biodistribution studies of the complexes in Swiss mice showed lower initial myocardial uptake for Ga-NODAGA-undecanoic acid (3.8±0.6%ID/g) and Ga-DTPA-undecanoic acid (1.3±0.5%ID/g) complexes in comparison to previously reported Ga-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 of Ga-NODAGA-undecanoic complex, which led to improved heart/non-target ratios of the complex over time in comparison to the other Ga complexes. Similarly, the DTPA complex exhibited increased washout from the liver in comparison to other Ga derivatives. The β oxidation mechanism in myocytes was investigated by isolating the myocardial extract post intravenous injection of the respective Ga 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 of Ga labeled fatty acids to achieve the desired myocardial imaging characteristics.