Eur J Nucl Med (1985) 10:4547 EuropeanN u c l e a r Journal of Medicine © Springer-Verlag 1985 Tumor localization of alpha-aminoisobutyric acid (AIB) in human melanoma heterotransplants Peter S. Conti 1, Emilia M. Sordillo 2, Peter P. Sordillo 3, and Bernard Schmall 4 Memorial Sloan-Kettering Cancer Center and Cornell University Graduate School of Medical Sciences, New York, USA Abstract, The nude mouse bearing a human tumor hetero- transplant is a useful model for studying the tumor localiza- tion of radiolabeled compounds. The biological tissue dis- tribution of carbon 14-labeled alpha-aminoisobutyric acid (AIB), a synthetic, nonmetabolized amino acid, was deter- mined in nude mice bearing human malignant melanoma heterotransplants in order to investigate the feasibility of using carbon 11 (~ 20.4 rain) -labeled AIB for the visualiza- tion of human melanoma in vivo with positron emission tomography (PET). Our laboratory has previously demon- strated the use of 11C-labeled AIB as a tumor-imaging agent in a number of animal tumor models. The mean rela- tive concentration of l~C-labeled AIB in tumor tissue at 45 rain 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 a XC_labele d AIB may be useful for the in vivo study of malignant mela- noma in humans. Alpha-aminoisobutyric acid (AIB), a synthetic, nonmetabo- lized 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~ 20.4 rain), 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 sar- coma, 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 pros- tatic adenocarcinomas have suggested that 11C_labele d AIB has potential as an in vivo tumor-imaging agent for carcino- ma of the prostate in humans [5]. The nude mouse bearing a human tumor heterotrans- plant has been shown to be useful as a model for studying the tumor localization of radiolabeled compounds, such as gallium citrate Ga67, cobaltous chloride Co57, cobaltous Neomycin Co57, and iodine norcholesterol I131 [2, 13]. 1 Pre-doctoral Research Fellow, Biophysics Laboratory 2 Pre-doctoral Research Fellow, Immunology Laboratory 3 Assistant Attending Physician, Solid Tumor Service; Research Associate, Biophysics Laboratory; Recipient- American Cancer Society Junior Clinical Faculty Award 4 Assistant Laboratory Member, Biophysics Laboratory Offprint requests to: Dr. Peter P. Sordillo, Biophysics Laboratory, Sloan-Kettering Institute, 1275 York Avenue, New York, NY 10021, USA Heterotransplants of malignant Schwannoma [13], non- Hodgkin's lymphoma [13], and undifferentiated lung carci- noma [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 malig- nant melanoma heterotransplants in order to investigate the feasibility of using 11C-labeled AIB for the study of malignant melanoma in vivo. Materials and methods Nude mice bearing human tumor heterotransplants Human malignant-melanoma cells from the SK-MEL-13 cell line [1] were cultured in minimal essential media plus 7.5% fetal calf serum supplemented with nonessential ami- no acids, penicillin, and streptomycin. Male Swiss nu/nu mice aged 5-7 weeks were subcutaneously implanted in the right anterior dorsum with a suspension of 5 × 10 6 melano- ma cells. Mice were housed in the animal facility at Memori- al Sloan-Kettering Cancer Center on laminar-flow shelves with 5-6 mice per cage, and fed Purina Mouse Chow and water ad libitum. In order to obtain a tumor growth curve, heterotransplants in five nude mice were observed over a period of 1 month following implantation, and the tumor areas (length × width) were measured with calipers every 2-3 days beginning 10 days after implantation, when the tumors first became palpable. The relative tumor a?ea was determined by calculating the ratios of measurements taken over period of I month to the value obtained at day 10. Thirty mice were studied with 14C-labeled AIB when the tumors measured approximately 1 cm at the point of grea- test diameter. Biological tissue distribution of l4C-labeled AIB 14C-labeled AIB (sp. act., 53 mCi/mmol) was obtained from New England Nuclear (Boston, Mass). Following the intra- cardiac injection of 2 ~Ci 14C-labeled AIB under ether anes- thesia, mice were killed by cervical dislocation at 5, 15, 30, 45, and 60 min postinjection, with six animals per time point. Blood and tissue samples were removed at necropsy, weighed, and immediately processed for liquid scintillation counting using Protosol tissue solubilizer with Econofluor and Biofluor scintillation cocktails obtained from New En- gland Nuclear. Samples were counted in a Packard-B2450 liquid scintillation counter. Counting efficiencies were de-