The pharmacokinetic characteristics of small peptides radiolabeled with technetium-99m, their physico-chemical properties and radiolabeling techniques are reviewed.
Methods: Physical and chemical characteristics which affect pharmacokinetics are discussed with particular reference to lipophilicity, charge and resistance to peptidases. General biodistribution, pharmacokinetics, metabolism and excretion characteristics, as well as tissue uptake kinetics are described. Methods of radiolabeling small peptides with 99mTc are reviewed, including discussion of chelating groups for technetium. Specific examples drawn either from the literature or from the 99mTc labeled peptides under development by Diatide are presented.
Result: Although lipophilicity and charge have an impact, the degree of resistance to peptidases is a key determinant of pharmacokinetic behavior. In general, pharmacokinetics and rate of tissue uptake are fast and metabolism occurs mainly via peptidase activity in the liver and kidneys. Although the route depends on a number of factors, excretion also usually is rapid. Chelating groups for 99mTc in the (+5) oxidation state are preferred. Site specific incorporation of the chelating groups during peptide synthesis is also preferred. Examples of renal imaging agents (MAG3), thrombus imaging peptides (P280 and P748), tumor imaging peptides (P587 and P829) and infection/inflammation imaging peptides (fMLF-type and P483H) are presented and discussed.
Conclusions: 99mTc labeled small peptides are characterized by rapid pharmacokinetics and tissue penetration. Furthermore, small peptides are readily synthesized and the desired pharmacokinetic behavior may be engineered into the molecule. They are well suited for development as radiopharmaceuticals.