Tumor localization of alpha-aminoisobutyric acid (AIB) in human melanoma heterotransplants

Abstract

The nude mouse bearing a human tumor heterotransplant is a useful model for studying the tumor localization of radiolabeled compounds. The biological tissue distribution of carbon 14-labeled alpha-aminoisobutyric acid (AIB), a synthetic, nonmetabolized amino acid, was determined in nude mice bearing human malignant melanoma heterotransplants in order to investigate the feasibility of using carbon 11 (t 1/2, 20.4 min)-labeled AIB for the visualization of human melanoma in vivo with positron emission tomography (PET). Our laboratory has previously demonstrated the use of 11C-labeled AIB as a tumor-imaging agent in a number of animal tumor models. The mean relative concentration of 14C-labeled AIB in tumor tissue at 45 min was 1.95 in this melanoma model. Tumor/blood and tumor/muscle ratios at 45 min postinjection were 5.42 and 12.2, respectively. These values suggest that 11C-labeled AIB may be useful for the in vivo study of malignant melanoma in humans. Alpha-aminoisobutyric acid (AIB), a synthetic, nonmetabolized amino acid, is thought to be actively accumulated into viable cells primarily by the A-type, or "alanine-prefering", amino acid transport system. AIB has been labeled with the short-lived, positron-emitting radionuclide, carbon 11 (t 1/2, 20.4 min), using a modified Bucherer-Strecker synthesis for amino acids. 11C-labeled AIB has been used to visualize tumors in dogs bearing spontaneous cancers, such as adenocarcinoma, lymphosarcoma, and osteogenic sarcoma, by utilizing positron-emission tomography (PET) and high-energy gamma (HEG) scintigraphy at the Sloan-Kettering Institute.(ABSTRACT TRUNCATED AT 250 WORDS)

Radiolabeled Amino Acids for Tumor Imaging with PET: Radiosynthesis and Biological Evaluation of 2-Amino-3-[18F]fluoro-2-methylpropanoic Acid and 3-[18F]Fluoro-2-methyl-2-(methylamino)propanoic Acid

“…The data obtained from normal rats with both [ 18 F] 5a and [ 18 F] 5b are similar to the reported distributions of [ 11 C]AIB in rats 21 and [ 14 C]AIB in mice, suggesting that these amino acids have similar transport mechanisms in vivo. This observation is consistent with the A type transport observed for both [ 18 F] 5a and [ 18 F] 5b in vitro.…”

“…A number of amino acids, including [ 11 C]α-aminoisobutyric acid (AIB), l -[ 11 C]methionine (Met), l -[ 18 F]fluoro-α-methyl tyrosine, O- (2-[ 18 F]fluoroethyl) tyrosine, and anti -1-amino-3-[ 18 F]fluorocyclobutyl-1-carboxylic acid (FACBC), have been successfully used for PET tumor imaging in humans. ,− AIB is a nonmetabolized α,α-dialkyl amino acid that is actively transported into cells primarily via the A type amino acid transport system. System A amino acid transport is increased during cell growth and division and has also been shown to be upregulated in tumor cells. − Studies of experimentally induced tumors in animals and spontaneously occurring tumors in humans have shown increased uptake of radiolabeled AIB in the tumors relative to normal tissue. ,− The N- methyl analogue of AIB, N- MeAIB, shows even more selectivity for the A type amino acid transport system than AIB. , N- MeAIB has been radiolabeled with carbon-11 and is metabolically stable in humans …”

“…1,2 The leading PET agent for diagnosis and imaging of neoplasms, 2-[ 18 F]fluorodeoxyglucose (FDG), also has limitations in the imaging of brain tumors. Normal brain cortical tissue shows high [ 18 F]FDG uptake as does inflammatory tissue, which can occur after radiation or surgical therapy; these factors can complicate the interpretation of images acquired with [ 18 F]FDG. [3][4][5][6] A number of reports indicate that PET and SPECT imaging with radiolabeled amino acids better define tumor boundaries within normal brain than CT, MRI, or [ 18 F]FDG, allowing better planning of treatment.…”

Non-natural amino acids for tumor imaging using positron emission tomography and single photon emission computed tomography

“…Initial studies with radiolabeled AIB in animals including murine melanoma xenograft and canine spontaneous tumor models demonstrated uptake in some but not all tumors [187,188]. Studies of [ 11 C]AIB in a small number of patients with soft tissue sarcomas and melanoma showed good uptake in the majority of the known tumors [177,178,189].…”

Radiohalogenated nonnatural amino acids as PET and SPECT tumor imaging agents

“…Several groups have used radiolabeled AIB for tumor imaging in animal models of brain and systemic tumors, including rodents with implanted glioma, colon, melanoma, and prostate tumors as well canines with spontaneously occurring tumors . In these studies, AIB generally demonstrated good tumor imaging properties, although the uptake in the spontaneous canine tumors was variable.…”