Rodney E. Bigler

Synthesis and body distribution of alpha-aminoisobutyric acid-L-11C in normal and prostate cancer-bearing rat after chemotherapy

This paper describes the synthesis of α-aminoisobutyric acid-l-11C (11C-AIB) and studies its body distribution in healthy and tumor-bearing animals. High tissue levels of 11C-AIB were found in organs with high metabolic activity (pancreas, liver, kidney). The prostate tumor 11C-AIB concentrations are significantly lower than that of pancreas, liver, and kidney, but increased when compared with normal prostate levels. Effective chemotherapy, which reduces tumor growth of two different prostate adenocarcinoma cell lines (R-3327-H, R-3327-G) also decreases 11C-AIB levels and the 11C-AIB prostate to tumor ratio.

Metabolic studies with radiobismuth. I. Retention and distribution of 206Bi in the normal rat.

The retention of tracer doses of bismuth citrate in mature female rats indicated that there were three compartments which cleared exponentially. Two of these compartments were renal and accounted for 30 percent and 44 percent of the administered dose. The biological half-times of bismuth in these compartments were less than 30 min and 13 hr, respectively. The nonrenal compartment accounted for the remainder of the dose and its retention half-time was 122 hr. The major site of bismuth accumulation was in the kidney. Autoradiographs showed

Skeletal distribution of mineralized bone tissue in humans.

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Tumor imaging with carbon-11 labeled alpha-aminoisobutyric acid (AIB) in a patient with advanced malignant melanoma

Bi to be localized in the renal cortex. The kidney is shown to secrete

Synthesis and quality assurance of [11C]alpha-aminoisobutyric acid (AIB), a potential radiotracer for imaging and amino acid transport studies in normal and malignant tissues

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Evaluation of [1-11C]-α-aminoisobutyric acid for tumor detection and amino acid transport measurement: spontaneous canine tumor studies

Bi into the urine and the renal extraction ratio is in excess of 0.92 for bismuth citrate. Whole-body scans at 24 hr do not reveal any other areas of concentration and demonstrate the applicability of this radionuclide as an imaging agent with conventional equipment. (auth)

EVIDENCE FOR THE CEREBRAL UPTAKE IN VIVO FROM TWO POOLS OF GLUCOSE AND THE ROLE OF GLUCOSE-6- PHOSPHATASE IN REMOVING EXCESS SUBSTRATE FROM BRAIN

Abstract— The data of Mechanik on the distribution of bone tissue mass have been analyzed statistically, summarized, and tabulated in a form convenient for reference. For comparison, analyses have been made of Mechaniks data on the distribution of bone marrow mass and of the data on the relation of skeletal mass or bone tissue mass to body weight as given by Mechanik in 1926 and by Borisov and Marei in 1974. About half of the bone tissue mass was in the limbs. The fraction in the arms and shoulder girdle was slightly greater in the males; that in the pelvic girdle was greater in the females. Standard deviations of the fractions of bone tissue in individual bones in each sex averaged about 10%, but ranged as high as 20%. Within this uncertainty, extrapolation to total body mineral may be made from measurements of a single bone. There were marked differences between the distributions of bone tissue and of marrow within the skeleton. Thus, the spine and pelvis contained 31% of the total marrow and 22% of the total bone tissue, while the skull and mandible contained only 7% of the total marrow but 15% of the total bone. While differences in other parts of the skeleton were smaller than these, it is clear that the weights of whole bones cannot properly be used in studies on bone mineral metabolism. The skeletal weight was rather constant at 13‐14% of the body weight in the males of the two populations over a wide age range. There was no sex difference in this parameter in the 4th and 5th decades of age, but the skeletons of older women tended to be lighter than those of contemporary men. Bone tissue average 8.4% of body weights in men and 6.9% in women, with considerable variation in the latter.

PET tomographic imaging of the human heart, pancreas, and liver with nitrogen-13 derived from [13N]-L-glutamate

A 29 year-old-man presenting with advanced metastatic malignant melanoma was successfully imaged using carbon-11 (11C) labeled alpha-aminoisobutyric acid (AIB), a synthetic, non-metabolized amino acid transported into viable cells by the A-type, or alanine-preferring, amino acid transport system. Tumor located in the hilum of the lung was well visualized with 11C-AIB prior to chemotherapy. A gallium image with liver subtraction using 99mTc-sulfur colloid demonstrated regions of increased activity in liver which correlated with regions of increased activity on the 11C-AIB liver image.

Estimation of skeletal calcium in humans by exhaled 37Ar measurement— Evaluation of the fast neutron dose requirement

Carbon-11 labeled alpha-aminoisobutyric acid (AIB), a synthetic amino acid, was prepared by the modified Bucherer-Strecker amino acid synthesis from acetone, ammonium carbonate and [11C]KCN in the presence of carrier KCN. This method results in the labeling of AIB in the carboxyl group. The label is stable in this position because AIB is not a metabolized after cellular uptake. AIB is rapidly accumulated in viable cells including malignant cells. Since it is a non-metabolized amino acid, AIB offers the possibility of studying amino acid transport in vivo without interference by radiolabeled metabolic products. Radiochemical yields of [11C]AIB of 35-60% have been obtained in 70-80 min with radiopurities greater than 99%. Carrier added syntheses gave 15-25 mCi of [11C]AIB with specific activities of 0.3 Ci/mmol. Our quality control program which insures that [11C]AIB is suitable for imaging studies in patients with cancer includes HPLC analyses of product identity and purity, apyrogenecity and isotonicity assays, and a sensitive test for cyanide.

Design for a multiple target system for a medical cyclotron

Alpha-aminoisobutyric acid (AIB), or α-methyl alanine, is a nonmetabolized amino acid transported into cells, particularly malignant cells, predominantly by the ‘A’ amino acid transport system. Since it is not metabolized, [1-11C]-AIB can be used to quantify A-type amino acid transport into cells using a relatively simple compartmental model and quantitative imaging procedures (e.g. positron tomography). The tissue distribution of [1-11C]-AIB was determined in six dogs bearing spontaneous tumors, including lymphosarcoma, osteogenic sarcoma, mammary carcinoma, and adenocarcinoma. Quantitative imaging with tissue radioassay confirmation at necropsy showed poor to excellent tumor localization. However, in all cases the concentrations achieved appear adequate for amino acid transport measurement at known tumor locations. The observed low normal brain (due to blood-brain barrier exclusion) and high (relative to brain) tumor concentrations of [1-11C]-AIB suggest that this agent may prove effective for the early detection of human brain tumors.