Biological evaluation of new [18F]F‐labeled synthetic amino acid derivatives as oncologic radiotracers. (11th July 2016)

• Record Type: Journal Article
• Authors: Kim, Yeseulmi; Lee, Sang Ju; Yook, Cheol‐Min; Oh, Seung Jun; Ryu, Jin‐Sook; Lee, Jong Jin
• Is Part Of: Journal of labelled compounds & radiopharmaceuticals. Volume 59:Number 10(2016)
• Page Start: 404
• Page End: 410
• Publication Date: 2016-07-11
• Subjects: (S)‐2‐amino‐(4‐([18F]fluoromethyl)‐1H‐1, 2, 3‐triazol‐1‐yl)alkyl acids -- positron emission tomography (PET) -- AMC -- click chemistry -- tumor -- amino acid -- transporter; Tracers (Chemistry) -- Periodicals; Radiopharmaceuticals -- Periodicals; 615.8424
• DOI: 10.1002/jlcr.3424
• Languages: English
• ISSNs: 0362-4803

Abstract

Abstract : The present study evaluated the tumoral uptake of the novel synthetic amino acid positron emission tomography (PET) tracers (S)‐2‐amino‐3‐(4‐([ 18 F]fluoromethyl)‐1 H ‐1, 2, 3‐triazol‐1‐yl)propanoic acid (AMC‐101), (S)‐2‐amino‐4‐(4‐([ 18 F]fluoromethyl)‐1 H ‐1, 2, 3‐triazol‐1‐yl)butanoic acid (AMC‐102), and (S)‐2‐amino‐5‐(4‐([ 18 F]fluoromethyl)‐1 H ‐1, 2, 3‐triazol‐1‐yl)pentanoic acid (AMC‐103), all of which are ( S )‐2‐amino‐(4‐([ 18 F]fluoromethyl)‐1 H ‐1, 2, 3‐triazol‐1‐yl)alkyl acids. In vitro cellular uptake was investigated using the rat glioma cell lines 9L and C6. In vitro competitive inhibition tests were performed to identify the involvement of specific amino acid transporters. In vivo dynamic PET images of 9L xenograft tumor‐bearing model mice were acquired over 2 h after AMC administration. [ 18 F]FDOPA PET studies were performed with and without S‐carbidopa pretreatment for comparison. All three AMCs exhibited good in vitro cell uptake through the L and alanine‐serine‐cysteine transporters and enabled clear tumor visualization on PET, leaving the brain devoid of the tracer. Thirty minutes after injection, the mean tumor standardized uptake values were 1.59 ± 0.05, 1.89 ± 0.27, and 1.74 ± 0.13 for AMC‐101, AMC‐102, and AMC‐103, respectively. Although the tumor uptake values of AMCs were lower than that of [ 18 F]FDOPA with S‐carbidopa pretreatment, AMCs enabled higher contrast images with lower background activity compared with [ 18 F]FDOPA with S‐carbidopa pretreatment. Our results indicate the potential uses of these new synthetic amino acids as oncologic radiotracers. Abstract : This study evaluates the tumoral uptake of the novel synthetic amino acid positron emission tomography (PET) tracers AMC‐101, ‐102, and ‐103, all of which are ( S )‐2‐amino‐(4‐([ 18 F]fluoromethyl)‐1 H ‐1, 2, 3‐triazol‐1‐yl)alkyl acids. All three AMCs exhibited good in vitro cell uptake through the L and ASC transporters and enabled clear tumor visualization on PET, leaving the brain devoid of the tracer. The results indicate the potential uses of these new synthetic amino acids as oncologic radiotracers.