Page 199 - Pharmaceutics IV (02-06-01305)

The dose can be much larger than doses than diagnostics .in the
case of 131 I the therapeutic dose is 5 to 10000 times the dose used
to assess organ function.

Most chemotherapeutic drugs & radiotherapeutic peptides are
small molecules ,low concentration of drug is obtainable at the
target site ,largely because of rapid excretion & metabolism by
the kidneys & liver .This limits the amount of drug available for
localization in the target site from the blood stream.

One strategy to increase the concentration of a dose -limited
,rapidly cleared radionuclide in a tumor was to couple it
covalently to a large molecule (e.g. MAB directed against tumor
marker on the surface of the tumor) . Because of its large size
these radionuclide conjugates are not rapidly excreted by the
kidneys: they are slowly removed from the systemic circulation
over several days by the reticuloendothelial system
(RES).Molecular weight ,lipophilicity ,&change of the targeting
agents are important property that influence hepatic & renal
excretion .Small water soluble peptides

Demonstrate effective excretion .

Targeting agent with a very high molecular weigh is thought to
reduce the ability of the agent to diffuse through the capillary
walls & thereby hinder the ability to target disseminated tumor
cells or normally vascularized tissues. enhanced circulation times
may result in higher tumor uptake.

Pegylated& other preventive modifications have demonstrated
some reduction in the RESs ability to uptake macromolecular
agents .

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