A major component of cancer cachexia is loss of muscle protein. This project seeks to evaluate a method to examine muscle wasting in cancer by quantitative in vivo study of amino acid transport and protein synthesis in skeletal muscle of human cancer patients using amino acids labeled with the short-lived, positron-emitting radionuclides N-13 and C-11. The present proposal is limited to studies of amino acid transport in skeletal muscle of two animal models: (a) fasting in dogs; and (b) cancer (VX2 carcinoma) in rabbits. The advantages of N-13 and C-11 as radiolabels are exploited in a relatively noninvasive technique for quantitative measurement of regional blood flow and transport. A true tracer of an amino acid labeled with N-13 and C-11 is coinjected with an intravascular tracer labeled with Tc-99m into the arterial blood supply of a peripheral muscle region, and the tracer kinetics are monitored by external gamma ray counting. Parameters specifically quantifying capillary and cell membrane transport are derived from the resulting data. Nitrogen-13 L-leucine and C-11 Yield-aminoisobutyric acid (a model substrate for the A, or alanine-preferring, system of amino acid transport) will be used in the animal models to examine the role of transport in regulating cellular uptake of branched-chain amino acids and release of alanine in skeletal muscle in acute and prolonged starvation, and precachetic and cachetic cancer. Plasma hormone levels and muscle protein synthesis rates will also be measured and examined for correlations with leucine and AlB transport parameters.
| Conlon, K C; Bading, J R; McDermott, E W et al. (1993) Extremity metabolism in the cachectic, VX-2 carcinoma-bearing rabbit. J Surg Res 55:330-7 |
| Conlon, K C; Corbally, M T; Bading, J R et al. (1990) Atraumatic endotracheal intubation in small rabbits. Lab Anim Sci 40:221-2 |
| Corbally, M T; Brennan, M F (1990) Noninvasive measurement of regional blood flow in man. Am J Surg 160:313-21 |
| Conlon, K C; Bading, J R; DiResta, G R et al. (1989) Validation of transport measurements in skeletal muscle with N-13 amino acids using a rabbit isolated hindlimb model. Life Sci 44:847-59 |
| Bading, J R; DiResta, G R; Corbally, M T et al. (1988) Fiberglass limb phantoms: fabrication and use for quantitative scintigraphy. Med Phys 15:215-20 |
