Claims for Patent: 5,573,748

Summary for Patent: 5,573,748

Title:	Radiolabeled technetium chelates for use in renal function determinations
Abstract:	The present invention is directed to novel radiopharmaceutical imaging agents incorporating Tc-99m as a radiolabel. In particular, the novel imaging agents disclosed herein have relatively high renal extraction efficiencies, and hence are useful for conducting renal function imaging procedures. The novel Tc-99m compounds of a present invention have the following general formula: wherein X is S or N; and wherein Y is H or wherein Y is R2 is -H, -CH2CO2H, -CH2CONH2, -CH2CH2CO2H, -CH2CH2CONH2, -CH3, -CH2CH3, CH2C6H5, or -CH2OH; and Z is -H, -CO2H, -CONH2, -SO3H, -SO2NH2, or -CONHCH2CO2H; and the Tc is Tc-99m; and water-soluble salts thereof. Of the foregoing, the presently preferred Tc-99m compound of the present invention is Tc-99m-mercaptoacetylglycylglycylglycine (Tc-99m-MAGGG). The present invention is also directed to novel chelating agents that may be reacted with Tc-99m to form the foregoing compounds. Such novel chelating agents have the following general formula. where X and Y have the same definitions as above, and wherein Y' is -H2 when X is N, or wherein Y' is -H, or a suitable protective group such as -COCH3, -COC6H5, -CH2NHCOCH3, -COCF3, or -COCH2OH when X is S. The present invention also provides methods for preparing and using the novel Tc-99m compounds.
Inventor(s):	Alan Fritzberg
Assignee:	University of Utah Research Foundation Inc
Application Number:	US08/262,947
Patent Claims:	1. A prepackaged kit for use in preparing a compound comprising technetium-99m, said compound having the general formula ##STR18## and water-soluble salts thereof, said prepackaged kit comprising: A container containing a selected quantity of a ligand of the general formula ##STR19## wherein X is S or N; and wherein Y1 is --H or a group which protects the sulfur from oxidation where X is S, or wherein Y1 is --H2 where X is N; and wherein Y is --H or wherein Y is ##STR20## and where R1 is --H, --CH3, or --CH2 CH3 ; R2 is --H, --CH2 CO2 H, --CH2 CONH2, --CH2 CH2 CO2 H, --CH2 CH2 CONH2, --CH3, --CH2 CH3, or --CH2 OH; and Z is --H, --CO2 H, --CONH2, --SO3 H, --SO2 NH2, or --CONHCH2 CO2 H; a suitable amount of a water soluble stannous salt to induce the reaction of said ligand with a technetium-99m pertechnetate salt; and a suitable amount of an intermediate exchange ligand to complex with said suitable amount of soluble stannous salt, wherein said container has sufficient volume for accepting a suitable amount of a water soluble technetium-99m pertechnetate salt to provide a desired level of radioactivity. 2. A prepackaged kit as defined in claim 1, wherein X is S. 3. A prepackaged kit as defined in claim 2, wherein, when Y1 comprises said group which protects the sulfur from oxidation, Y1 is --COCH3, --COC6 H5, --CH2 NHCOCH3, --COCF3, --COCH2 CO2 H, or --COCH2 OH. 4. A prepackaged kit as defined in claim 2, wherein Y' is --COC6 H5, and Y is --CH2 CO2 H. 5. A prepackaged kit as defined in claim 2, wherein Y is --CHCH3 CO2 H; --CH(CH2 CONH2)CO2 H; or --CH(CH2 CH2 CONH2)COOH. 6. A prepackaged kit as defined in claim 2, wherein the intermediate exchange ligand is acetate, glycine, citrate, malonate, gluconate, tartrate, malate, lactate, hydroxyisobutyrate, pyrophosphate, N-methyl N,N'-bis(2hydroxyethyl)ethylenediamine, or glucoheptonate.