No abstract

No abstract

Mouse monoclonal antibody TA99 detects a 70-kDa pigmentation-associated glycoprotein in human melanoma cell lines. The antigen cannot be detected on the cell surface by sensitive rosetting techniques or absorption studies, nor can it be detected as a secreted product in culture fluids. Contrary to expectation, I251-labeled TA" specifically localized to pigmented human melanoma transplants in nu/nu mice; no localization to nonpigmented melanoma or control tumors was found. Tumor imaging was initially obscured by circulating I251-labeled TA99 during the first 6 days after antibody injection. With clearance of sI-labeled TA99 from the blood (half-life, 4-7 days), specific tumor images could be clearly dermed by day 13. Due to the persistence of 125I-labeled TA99 at the tumor site (8.9% of the injected dose at 1 week and 4.6% at 8-10 weeks), images were obtainable for up to 10 weeks. At 8-10 weeks, the tumor/blood ratio was 104-105, and the tumor/normal tissue ratio ranged from 102 to 105. In view of these findings, antibodies detecting intracellular antigens may have a role in tumor imaging and therapy.

No abstract

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.

This paper describes the synthesis of alpha-aminoisobutyric acid-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.

Alpha-aminoisobutyric acid (AIB), or alpha-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.

Potassium 38 emits a 2.68-MeV (max) positron, followed promptly by a 2.17-MeV gamma-ray in 99.8% of its disintegrations. A positron is emitted also, followed by a 3.94-MeV gamma-ray, in 0.2% of the decays. The pairs of 511-keV PET +/- gamma-quanta, which are emitted at 180 +/- 0.3 degrees to each other, are in true coincidence with the prompt gamma-rays emitted by the daughter nucleus, within the resolving time of PET instrumentation. Studies made with phantoms by means of a commercial version of the MGH PET camera demonstrated that quantitatively satisfactory images are derived, despite the presence of the prompt gamma-rays. Two-dimensional (2-D) focal-plane images reveal high uptake of 38K promptly in the myocardium of dogs, under barbiturate sedation. Third-dimensional (3-D) transverse section PET tomographic images, through four 1.0-cm-thick heart "slices" orthogonal to the plane of the 2-D images and with 1.4-cm sequential spacing, show 38K uptake to be concentrated especially highly in the left ventricle, as expected. Peak levels of activity were observed over the myocardium at 12 s after intravenous bolus injection of ionic 38K. Dynamic mode 2-D images were taken at intervals as short as 0.5 s and extending to 1 h.