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The United States of America as Represented by the Secretary of

The United States of America as Represented by the Department of Health

The United States of America as Represented by the Secretary of Health

Otto A Gansow

Martin Wade Brechbiel

Mette Strand

Krishan Kumar

Michael A Magerstadt

The subject matter of the present invention relates to bifunctional cyclohexyl DPTA ligands and methods for utilizing these compounds.

Bifunctional DTPA-type ligand

The invention is a chelate of formula I: ##STR1## wherein R.sub.1-4 is --CH.sub.2 COOH;

Complexes of functionalized tetraazacyclododecane chelates with bismuth,

New polysubstituted diethylenetriaminepentaacetic acid chelates and protein conjugates of the same are described together with the methods of preparing such compounds. A method of delivering radiolabelled compound of the present invention to a target site while minimizing the distribution of the compound to non-targeted organs or tissues is also disclosed.

Backbone polysubstituted chelates for forming a metal chelate-protein

A process for synthesizing a 12 membered ring tetraaza macromolecule comprising. The process involves condensing an amide of ethylene diamine having a general formula A: ##STR1## wherein n is an integer from 1 to 5 and w is a member selected from the group consisting of --NO.sub.2, --NH.sub.2, --NCS, --COOH, --OCH.sub.2 OOCH.sub.3, --NCOCH.sub.2 --Z with Z being a member selected from the group consisting of Br and I with a nitrogen blocked active ester of a general formula B: ##STR2## wherein PG is an amino protecting group and E is a leaving group.

Process for synthesizing macrocyclic chelates

A method of forming a novel metal chelate protein conjugate is described. Also described are metal chelates and precursor compounds to the metal chelates. The novel metal chelate protein conjugates are particularly useful in the diagnostic imaging of tumors and in tumor therapy.

Metal chelate protein conjugate

Methods of manufacturing and purifying metal chelate conjugated monoclonal antibodies are described. The chelated metal may be one which emits alpha, beta or gamma radiation, or positrons. Alternatively, the metal can be one which is fluorogenic or paramagnetic. The conjugates are suited for diagnostic and therapeutic uses.

Metal chelate conjugated monoclonal antibodies

Therapeutic and diagnostic methods employing metal chelate conjugated monoclonal antibodies are described. Metals employed in therapeutic conjugated antibodies include alpha particle, beta particle or Auger electron emitting isotopes. Diagnostic methods may be either in vivo or in vitro. Chelated metals employed in diagnostic techniques may include, inter alia, gamma or positron emitting metals as well as fluorogenic or paramagnetic metals.

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Washington, DC, United States of America

Otto A Gansow