Glucose is transported in crustacean hepatopancreas and intestine by Na+-dependent co-transport, while Na+-dependent D-fructose influx has only been described for the hepatopancreas. It is still unclear if the two sugars are independently transported by two distinct cotransporter carrier systems. In this study lobster (Homarus americanus) hepatopancreas brush border membrane vesicles (BBMV) were used to characterize, in detail, the cation-dependency of both D-[3H] glucose and D-[3H] fructose influxes, while in vitro perfused intestines were employed to determine the nature of cation-dependent sugar transport in this organ. Over the sodium concentration range of 0-100 mM, both 3H-D-glucose and 3H-D-fructose influxes (0.1 mM; 1 min uptakes) by hepatopancreatic BBMV were hyperbolic functions of [Na+], exhibiting Km values of 2.30 ± 0.59 and 2.58 ± 0.95 mM, respectively. D-[3H] glucose and fructose influxes by hepatopancreatic BBMV over a potassium concentration range of 15-100 mM were hyperbolic functions of [K+], exhibiting Km values of 9.85 ± 0.41 and 12.6 ± 0.80 mM respectively. Both sugars displayed significant (p < 0.01) Na+/K+-dependent and Na+-independent uptake processes. Transepithelial 25 μM D-[3H] glucose and D-[3H] fructose fluxes across lobster intestine over a luminal sodium and potassium concentration range of 0 – 50 mM and 5-100 mM, respectively, were hyperbolic functions of luminal [Na+] and [K+]. As with hepatopancreatic sugar transport, transepithelial intestinal sugar transport exhibited both significant (p < 0.01) Na+/K+-dependent and Na+-independent processes. Results suggest that both D-glucose and D-fructose are transported by a single carrier process in each organ with sodium being the preferred cation for both sugars in the hepatopancreas, and potassium being the preferred cation for both sugars in the intestine.

For any drug candidate to be approved by the U.S. Food and Drug Administration, it must meet strict standards for safety and efficacy. While the field of nuclear medicine is over 100 years old, traditional methods such as external beams or systematic administration have rarely met these standards or have limited application. Ligand-targeted therapy and diagnostics, or “theranostics,” has emerged in the past several decades as an exciting field that offers new possibilities to design drugs that are both safe and effective. When applied to nuclear medicine, the field of ligand-targeted radioactive theranostics is younger still, with many critical lessons being discovered and applied currently. This dissertation outlines the necessary principles of radioactive theranostic drug design, then demonstrates the application of several more recent techniques to improve both the efficacy and safety of radioactive theranostics targeting two high priority oncological targets: fibroblast activation protein alpha and folate receptor.