Resolution Pharmaceuticals Inc.

Hsc Research Development Corporation

Kronem Systems, Inc.

Resolutions Pharmaceuticals, Inc.

Alfred Pollak

Anne Goodbody

Robert Dunn-Dufault

John Thornback

Robert A Kirby

Susan H Peers

Ramon A Evangelista

Suman Rakhit

Ernest Wong

Tam Nguyen

Eva F Templeton

Theresa Fauconnier

Michael Maszkiewicz

David Roe

A peptide-chelator conjugate that is useful for imaging sites of inflammation in humans comprises a metal chelator coupled to a glycopeptide antibiotic. The metal chelator and the glycopeptide are coupled by a linking group. The linking group may be the divalent radical NH--(CH.sub.2).sub.3 --NH. Alternatively the linking group may be .beta.Ala.sub.3 LysGly-OH and the glycopeptide may be coupled to the N.sup..epsilon. of Lys. A method of imaging a site of inflammation is also provided. The method comprises the step of administering a diagnostically effective amount of a composition comprising a glycopeptide-chelator conjugate comprising a metal chelator coupled to a glycopeptide antibiotic. The glycopeptide-chelator conjugate is in a form complexed with a diagnostically useful metal or an oxide or nitride thereof.

Glycopeptide-chelator conjugates

Described herein are D4 receptor-selective compounds of the formula: ##STR1## wherein R.sup.1 is selected from H and an acid labile protecting group; and R.sup.2 and R.sup.3 are independently selected from H, radioisotopic halo, loweralkoxy and tri(loweralkyl)tin; and salts, solvates or hydrates thereof. Also described is the use of these compounds as pharmaceuticals to treat indications for which a dopamine D4 receptor antagonist is indicated. Radiolabeled compounds are useful particularly to image localization of D4 receptor in the human brain, and can therefore aid in the diagnosis of schizophrenia and other medical conditions in which the D4 receptor is implicated.

Dopamine D4 receptor ligands

Peptide derived radionuclide chelators

Peptide-chelator conjugates are provided that when labelled with a traceable metal are useful for diagnostic imaging of sites of inflammation. The peptide component is an antagonist of the naturally occurring tetrapeptide tuftsin while the chelator component serves as a labelling site for metals, in particular radionuclide metals such as technetium-99 m.

Peptide-chelator conjugates

Radionuclide chelating compounds are provided for conjugation to targetting molecules such as proteins, peptides or antibodies. The resulting labelled targetting molecules may be used in diagnosis and therapy.

Hydrazino-type N.sub.2 S.sub.2 radionuclide chelating compounds

Detectably labelled non-receptor mediated cell-associating compounds are provided for use in the diagnostic imaging of target sites in a mammal. Cell-associating compounds may be directly labelled, or labelled via a chelating compound to form a conjugate. Such cell-associating compounds are particularly useful to image target sites such as tumour sites and sites of infection.

Non-receptor cell mediated imaging agents

Compounds useful for high resolution diagnostic imaging incorporate an imaging agent having a chelator that is linked by a metal-cleavable bond to a ligand that has affinity for a site removed from the site of diagnostic interest. Upon labelling, the ligand is cleaved leaving the labelled imaging agent free to localize at the site of diagnostic interest unhindered, while the ligand and any unlabelled imaging agent is sequestered to the removed site. By sequestering unlabelled imaging agent, the labelled imaging agent does not compete to occupy the site of interest, resulting in images of enhanced resolution.

Sequestered imaging agents

Immobilized labelling method

For use in imaging sites of diagnostic interest within the body, the present invention provides radionuclide chelators, optionally coupled to targeting molecules such as peptides of the formula: ##STR1##

Herein described are radiolabeled compounds and their precursors useful to image D4 receptors in vivo, of the formula: ##STR1## wherein R is selected from iodo, tri(loweralkyl)tin and a radioisotopically labeled iodide and R.sup.1 is selected from H and alkoxycarbonyl, with the proviso that R is not iodo when R.sup.1 is H. The radiopharmaceutical compounds are useful particularly to image localization of D4 receptor in the human brain, and can therefore aid in the diagnosis of schizophrenia and other medical conditions in which the D4 receptor is implicated.

Radiolabeled D4 receptor ligands

Non-receptor mediated imaging agents

Peptide-chelator conjugates are provided that when labelled with a traceable metal are useful for diagnostic imaging of sites of inflammation. The peptide component is an antagonist of the naturally occurring tetrapeptide tuftsin while the chelator component serves as a labelling site for metals, in particular radionuclide metals such as technetium-99m.

Radionuclide chelating compounds are provided for conjugation to targeting molecules such as proteins, peptides or antibodies. The resulting labeled targeting molecules may be used in diagnosis and therapy.

Growing community of inventors

Toronto, Canada

Alfred Pollak