Monoclonal antibodies (MoAbs) were proposed as candidates for selective tumor targeting based on their high binding affinity for tumors and the absence of binding by normal tissue. However, the exclusive and complete transport of the drug have been found lacking in the use of intact MoAbs, especially in the case of solid tumors. Smaller fragments that maintained the desiderable tumor targeting characteristics appear to have an advantage because of the increase in whole body clearance and the shorter time to maximum target to non-target ratio. But the binding to normal tissue increases as the molecular weight or size decreases, especially in the kidney, because the glomerular sieving coefficient increases. We have used two approaches to overcome the normal tissue binding: a) the use of lysine to block the uptake of the Low Molecular Weight Proteins (LMWP) in the proximal tubules and b) the labeling of different amino acids in the LMWP to alter the residence time in the kidney. The combination of these two methods, blocking the uptake with lysine and shortening the residence time of the radioactive compound produced in the kidney, can lead to substantially decreased normal kidney targeting. The lysine paradigm was effectively demonstrated using 18F-labeled anti-Tac dsFv. Shortening the residence time was illustred by comparing the kinetics of the lysine catabolite versus the methionine metabolite. Furthermore, the rapid pharmacokinetics of the LMWP are consistent with the use of the shorter half-lives of PET radionuclides and the concomitant increase in quantitation and sensitivity afforded by PET.