Myocardial uptake and biodistribution of newly designed technetium-labelled fatty acid analogues

Abstract

The excellent extraction rates found for '4+1' 99mTc-FAs indicate possibly promising structures for innovative myocardial tracers.

Technetium-99m Labeled Fatty Acid Analogues for SPECT Imaging in Heart and Liver

“…The '3 + 1' mixed-ligand approach for technetium-labeled fatty acid ( Figure 5c) is similar to the '4 + 1' mode, which the metal core in the oxidation states +5 is wrapped with both a tridentate component consisting of the sulfido-dithiolate donor and a monodentate sulfhydryl group at the end position of fatty acid chain [32][33][34]. The '3 + 1' and the '4 + 1' mixed-ligand technetium-labeled fatty acids were investigated by the biodistribution in guinea pigs and and the isolated heart model [31].…”

Cysteine Derivatized 99mTc-Labelled Fatty Acids as β-Oxidation Markers

“…Once inside the myocardium, where they are transported by passive diffusion or by protein transporters [2], they can either be catabolized through β-oxidation which degrades them by removing two-carbon units, or they can be stored in the form of triglycerides for future use as energy supplies [3]. Under ischaemic conditions oxidation of fatty acids is suppressed and glycolysis and glycogen breakdown are used as an energy source [4]. Therefore, the metabolism of fatty acids and its suppression during ischaemia is a sensitive marker for the normal function of the heart.…”

Syntheses and biological evaluation of99mTc-HYNIC-fatty acid complexes for myocardial imaging

“…Several efforts have been put forward by researchers worldwide to develop 99m Tc-labeled fatty acid radiotracers to image the abnormalities related to the myocardium. [9][10][11][12][13][14][15][16][17][18][19] Although 99m Tc-radiotracers based on fatty acids have proved their efficacy to target myocardium in animal models, low myocardial uptake and signicant non-target uptake limited their further evaluation for clinical use. Continuous efforts are being made to design a 99m Tc-fatty acid radiotracer with better myocardial uptake and rapid clearance from non-target organs to obtain clinically acceptable heart-tonon-target ratios.…”

“…Similarly, the nature of 99m Tc-core is also found to affect the in vivo distribution and clearance of the radiotracer, and offers an additional route to achieve desirable pharmacokinetics. In this regard, several fatty acid complexes with different 99m Tc-cores such as [ 99m TcN(PNP)] 2+ , 9,10 99m Tc-4+1, [11][12][13] [ 99m Tc(CO) 3 cyclopentadienyl], 14 [ 99m Tc(CO) 3 (H 2 O) 3 ] + , 15 [ 99m TcO] 3+16- 19 have been prepared and evaluated. However, to the best of our knowledge fatty acids labeled with 99m Tc through HYNIC bifunctional chelator has not been reported.…”

“…Though, fatty acids of 15-21 carbon chain lengths have been documented to exhibit highest myocardial extraction, 41 however, in the present study, fatty acids with chain lengths of 11 and 12 carbon [11C-FA (1a)] and [12C-FA (2a)] are chosen, considering the fact that among the 99m Tclabeled metabolic myocardial imaging agents reported so far, highest myocardial uptake was shown by 11 and 12 carbon fattyacids. 9,12,13 Use of the HYNIC-BFCA and different co-ligands such as tricine, EDDA and TPPTS allows modulation of the lipophilicities of the 99m Tc-HYNIC complexes and also tailoring the in vivo pharmacokinetic behavior of the complexes. The two fatty acids (1a, 2a) were synthetically modied at the u-carbon to yield HYNIC-fatty acid conjugates [11C-FA-HYNIC (1c) and 12C-FA-HYNIC (2c)].…”