Syntheses and biological evaluation of ⁹⁹ᵐTc-HYNIC-fatty acid complexes for myocardial imaging
2015
Mathur, Anupam | Sharma, Abhishek K. | Murhekar, V. V. | Mallia, Madhava B. | Pawade, Shital | Sarma, H. D. | Chaudhari, Pradip | Sachdev, S. S. | Banerjee, Sharmila
The aim of the present study is to identify a ⁹⁹ᵐTc-labeled fatty acid tracer which could be a possible substitute of the widely used ¹²³I-labeled fatty acids in studying myocardial metabolism and in detection of myocardial abnormalities in high-risk patients. The relevance of the study stems from the fact that in terms of wider applicability, a ⁹⁹ᵐTc-tracer is expected to be more advantageous compared to that of a ¹²³I-based one. Two fatty acid (FA)-hydrazinopyridine-3-carboxylic acid (HYNIC) conjugates (11C-FA-HYNIC and 12C-FA-HYNIC) were synthesized and radiolabeled with ⁹⁹ᵐTc using two different co-ligands system viz. tricine/ethylenediamine diacetic acid (EDDA), and tricine/trisodium triphenylphosphine-3,3′,3′′-trisulfonate (TPPTS), to yield four radiolabeled complexes. While all four ⁹⁹ᵐTc-HYNIC-complexes showed uptake in the myocardium, 12C-FA-HYNIC-⁹⁹ᵐTc-EDDA complex showed higher uptake and retention in myocardium compared to other complexes. In general, uptake of the ⁹⁹ᵐTc-complexes in non-target organs was lower than that of ¹²⁵I-iodophenyl pentadecanoic acid (IPPA). The 12C-FA-HYNIC-⁹⁹ᵐTc-EDDA complex, additionally exhibited lower liver accumulation compared to that of ¹²⁵I-IPPA. Though these features were favorable for cardiac imaging, the heart-to-blood ratio of the complexes were low (<1). Nevertheless, a dynamic SPECT image of 12C-FA-HYNIC-⁹⁹ᵐTc-EDDA complex in Swiss mouse showed delineation of its myocardium from proximal non-target organs. The results merit further screening of synthetically modified ⁹⁹ᵐTc-HYNIC fatty acids for myocardial imaging.
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