Biological evaluation of new [¹⁸F]F‐labeled synthetic amino acid derivatives as oncologic radiotracers

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)-1H-1,2,3-triazol-1-yl)propanoic acid (AMC-101), (S)-2-amino-4-(4-([(18) F]fluoromethyl)-1H-1,2,3-triazol-1-yl)butanoic acid (AMC-102), and (S)-2-amino-5-(4-([(18) F]fluoromethyl)-1H-1,2,3-triazol-1-yl)pentanoic acid (AMC-103), all of which are (S)-2-amino-(4-([(18) F]fluoromethyl)-1H-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.

Click Chemistry and Radiochemistry: An Update

“…In these scenarios, the CuAAC ligation can be particularly useful, as azide- or alkyne-bearing prosthetic groups can be radiolabeled and then clicked to vectors in a one-pot two-step schema. This approach is especially popular in the synthesis of 18 F-labeled agents, as evidenced by a large library of 18 F-labeled clickable groups that includes [ 18 F]­fluorobenzyl azides, , azide- and alkyne-modified [ 18 F]­fluoropyridines, [ 18 F]­fluoroalkyl azides, ,− [ 18 F]­fluorocarbohydrate azides, ,,− [ 18 F]­fluoropolyoxyethylene azides, ,,− 3-[ 18 F]­fluoropropyne, 5-[ 18 F]­fluoropentyne, , ethynyl-4-[ 18 F]­fluorobenzene, and [ 18 F]­AMBF 3 . , In one recent example, Wang et al reported the synthesis of a modular scaffold for combined near-infrared (NIR) fluorescence and PET imaging via the CuAAC-mediated modification of an azide-bearing NIR dye with an 18 F-labeled alkyne . The work of Walker et al provides a particularly fine example of the pros and cons of a two-step, CuAAC-driven approach to radiofluorination (Figure ).…”

Tinker, Tailor, Soldier, Spy: The Diverse Roles That Fluorine Can Play within Amino Acid Side Chains

“…18 F-Radiolabelled amino acids can be valuable agents for the diagnosis and visualization of cancer. Tumour cells have high biosynthetic demand [149], and one way that they can secure an increased supply of biosynthetic building blocks is by upregulating amino acid transporter proteins [150,151]. Thus, 18 F-radiolabelled amino acids often selectively accumulate in tumours, where their presence can be detected by positron emission tomography.…”

“…This important radiotracer is particularly valuable for the imaging of brain cancers as the amino acid transporter proteins mentioned above enable this tracer to efficiently cross the blood-brain barrier [150,[152][153][154]. Prosthetic groups for the radiolabelling of several other amino acids besides tyrosine [155][156][157] have also been developed, taking advantage of the reactivity of the side chains of serine (41) [158], threonine (42) [158], tryptophan (43) [159], cysteine (44) [160,161], and ornithine (45) [151,162] (Figure 3a). Certain more elaborate prosthetic groups afford the alternative possibility of late-stage fluorination through 18 F/ 19 F isotopic exchange (e.g., 46-47) [163,164].…”