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

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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 [3]. 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 [7, 8]. 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 [9]. Tissue distribution studies in rats bearing transplanted Dunning-R3327G and-R3327H prostatic adenocarcinomas have suggested that 11C-labeled AIB has potential as an in vivo tumor-imaging agent for carcinoma of the prostate in humans [5]. The nude mouse bearing a human tumor heterotransplant has been shown to be useful as a model for studying the tumor localization of radiolabeled compounds, such as gallium citrate Ga 67, cobaltous chloride Co 57, cobaltous bleomycin Co 57, and iodine norcholesterol I131 [2, 13]. Heterotransplants of malignant Schwannoma [13], non-Hodgkin's lymphoma [13], and undifferentiated lung carcinoma [2] have been studied with radiolabeled compounds in the nude mouse. In this study, the biological tissue distribution of carbon 14-labeled AIB was determined in nude mice bearing malignant melanoma heterotransplants in order to investigate the feasibility of using 11C-labeled AIB for the study of malignant melanoma in vivo.