99mTc(CO)3-15-[N-(Acetyloxy)-2-picolylamino]pentadecanoic Acid:  A Potential Radiotracer for Evaluation of Fatty Acid Metabolism

Lee, Byung Chul; Kim, Dong Hyun; Lee, Jae Hak; Sung, Hyun Ju; Choe, Yearn Seong; Yoon, Dae; Lee, Kyung-Han; Choi, Yong; Kim, Byung‐Tae

doi:10.1021/bc060299w

Cited by 26 publications

(20 citation statements)

References 26 publications

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“…This finding is consistent with literature reports that correlate myocardial uptake with the length of the fatty acids chain [29,35]. The initial heart uptake values in this study were lower compared to the 123 I-IPPA in clinical use (9.51 %ID/g) [37], however, it is comparable to the values of other 99m Tc-labelled fatty acid analogues in mice [27,29,31,37,38,[41][42][43][44]. The cardiac retention observed for 99m Tc-Cys-FA16 (2.31 ± 0.09 %ID/g) was higher than that observed for 99m Tc-Cys-FA11 (0.60 ± 0.02 %ID/g) at 15 min post injection, possibly due to its longer aliphatic side chain that prolongs metabolism.…”

Section: Resultssupporting

confidence: 92%

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

et al. 2019

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With the aim of developing 99mTc-labeled fatty acids intended for myocardial metabolism imaging we report herein the synthesis and characterization of two novel derivatives of undecanonoic and hexadecanonoic acid that have been functionalized at the ω-site by cysteine through the formation of a thioether bond (Cys–FA11 and Cys–FA16). Equimolar amounts of each ligand and the [NEt4]2[Re(CO)3Br3] precursor generated the respective hexacoordinated neutral complexes in which the ligand coordinated to the metal through the SNO donor system of cysteine. The rhenium complexes were characterized by elemental analysis, IR and NMR spectroscopies. The analogous technetium-99m complexes, 99mTc–Cys–FA11 and 99mTc–Cys–FA16 were prepared by incubation of the ligand with the precursor [99mTc(CO)3(H2O)3]+ (radiochemical yield ≥98%). Their structure was established by comparative HPLC techniques. In vivo studies in mice showed high initial heart uptake for both 99mTc complexes (7.4 ± 0.53 and 7.07 ± 0.73 percentage of injected dose (%ID)/g at 1 min post injection. Rapid clearance (0.60 ± 0.02 %ID/g) was observed for 99mTc–Cys–FA11 while the clearance of the longer fatty acid 99mTc–Cys–FA16 was slower (2.31 ± 0.09 %ID/g at 15 min p.i.). Metabolite analysis study indicated that complexes were catabolized through the β-oxidation process.

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Section: Resultssupporting

confidence: 92%

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

et al. 2019

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“…The coordination of the 99m Tc radioisotope to the di-(2-picolyl)amine moiety of the TSPO-ligand 3 was obtained in aqueous media by using the fac -[ 99m Tc(H 2 O) 3 (CO) 3 ] + synthon, which can be readily generated from 99m TcO 4 − and CO gas in the presence of NaBH 4 [20,31]. …”

Section: Resultsmentioning

confidence: 99%

“…In addition, the tricarbonyl technetium-99m ( 99m Tc-(CO) 3 ) unit has been shown to be useful for introducing 99m Tc into biomolecules because of its high chemical stability and small size. In order to take advantage of molecular imaging techniques with 99m Tc-(CO) 3 , many low-molecular weight 99m Tc(I)-complex with tridentate ligands have been developed and used for the preparation of 99m Tc-(CO) 3 -labeled radiotracers [19,20,21,22,23,24]. …”

Section: Introductionmentioning

confidence: 99%

Synthesis and Evaluation of Tricarbonyl 99mTc-Labeled 2-(4-Chloro)phenyl-imidazo[1,2-a]pyridine Analogs as Novel SPECT Imaging Radiotracer for TSPO-Rich Cancer

Choi

Iacobazzi

Perrone

et al. 2016

IJMS

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The 18-kDa translocator protein (TSPO) levels are associated with brain, breast, and prostate cancer progression and have emerged as viable targets for cancer therapy and imaging. In order to develop highly selective and active ligands with a high affinity for TSPO, imidazopyridine-based TSPO ligand (CB256, 3) was prepared as the precursor. 99mTc- and Re-CB256 (1 and 2, respectively) were synthesized in high radiochemical yield (74.5% ± 6.4%, decay-corrected, n = 5) and chemical yield (65.6%) by the incorporation of the [99mTc(CO)3(H2O)3]+ and (NEt4)2[Re(CO)3Br3] followed by HPLC separation. Radio-ligand 1 was shown to be stable (>99%) when incubated in human serum for 4 h at 37 °C with a relatively low lipophilicity (logD = 2.15 ± 0.02). The rhenium-185 and -187 complex 2 exhibited a moderate affinity (Ki = 159.3 ± 8.7 nM) for TSPO, whereas its cytotoxicity evaluated on TSPO-rich tumor cell lines was lower than that observed for the precursor. In vitro uptake studies of 1 in C6 and U87-MG cells for 60 min was found to be 9.84% ± 0.17% and 7.87% ± 0.23% ID, respectively. Our results indicated that 99mTc-CB256 can be considered as a potential new TSPO-rich cancer SPECT imaging agent and provides the foundation for further in vivo evaluation.

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“…Several 99m Tc labeled fatty acids following different 99m Tc chemistries viz. oxotechnetium (V) core ([ 99m Tc = O] 3+ ), 11 nitrido core ([ 99m TcN(PNP)] 2+ ), 12,13 99m Tc-4 + 1 mixed ligand approach, 14,15 tricarbonyl core ([ 99m Tc(CO) 3 (H 2 O) 3 ] + ), 16,17 cyclopentadienyl tricarbonyl technetium ( 99m Tc-CpTT) core, [18][19][20] and 99m Tc-HYNIC, 21 were developed and evaluated in past but all lacked favorable characteristics for in vivo imaging. 99m Tc cores/ BFCAs alter in vivo pharmacokinetic behavior of fatty acids of identical chain lengths.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and biodistribution studies of ^99mTc labeled fatty acid derivatives prepared via “Click approach” for potential use in cardiac imaging

Das

Mathur

Sakhare

et al. 2018

Labelled Comp Radiopharmac

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I-Iodophenylpentadecanoic acid (IPPA) is a metabolic agent used in nuclear medicine for diagnosis of myocardial defects. Efforts are underway worldwide to develop a Tc substitute of the above radiopharmaceutical for the aforementioned application. Herein, we report synthesis and biodistribution studies of Tc labeled fatty acids (8, 11, and 15 carbons) obtained via "click chemistry" for its potential use in myocardial imaging. ω-Bromo fatty acids (8C/11C/15C) were synthetically modified at bromo terminal to introduce a heterocyclic triazole with glycine sidearm in a five step procedure. Modified fatty acids were subsequently radiolabeled with preformed [ Tc(CO) ] synthon to yield the desired fatty acid complexes which were evaluated in Swiss mice. All the radiolabeled complexes were obtained with radiochemical purities >80%, as characterized by HPLC. Biodistribution studies of all three complexes in Swiss mice showed myocardial uptake of ~6-9% ID/g at 2 minutes post-injection, close to I-IPPA (~9% ID/g). Complexes exhibited significant retention in the myocardium up to 30 minutes (~1% ID/g) but were lower to the standard agent (~7% ID/g). Similar uptake of activity in myocardium for the newly synthesized complexes in comparison to I-IPPA along with favorable in vivo pharmacokinetics merits potential for the present "click" design of complexes for myocardial imaging.

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⁹⁹^mTc(CO)₃-15-[N-(Acetyloxy)-2-picolylamino]pentadecanoic Acid: A Potential Radiotracer for Evaluation of Fatty Acid Metabolism

Cited by 26 publications

References 26 publications

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

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

Synthesis and Evaluation of Tricarbonyl 99mTc-Labeled 2-(4-Chloro)phenyl-imidazo[1,2-a]pyridine Analogs as Novel SPECT Imaging Radiotracer for TSPO-Rich Cancer

Synthesis and biodistribution studies of ^99mTc labeled fatty acid derivatives prepared via “Click approach” for potential use in cardiac imaging

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99mTc(CO)3-15-[N-(Acetyloxy)-2-picolylamino]pentadecanoic Acid: A Potential Radiotracer for Evaluation of Fatty Acid Metabolism

Cited by 26 publications

References 26 publications

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

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

Synthesis and Evaluation of Tricarbonyl 99mTc-Labeled 2-(4-Chloro)phenyl-imidazo[1,2-a]pyridine Analogs as Novel SPECT Imaging Radiotracer for TSPO-Rich Cancer

Synthesis and biodistribution studies of 99mTc labeled fatty acid derivatives prepared via “Click approach” for potential use in cardiac imaging

Contact Info

Product

Resources

About

⁹⁹^mTc(CO)₃-15-[N-(Acetyloxy)-2-picolylamino]pentadecanoic Acid: A Potential Radiotracer for Evaluation of Fatty Acid Metabolism

Synthesis and biodistribution studies of ^99mTc labeled fatty acid derivatives prepared via “Click approach” for potential use in cardiac imaging