Bracco Imaging S.p.a.

Nihon Medi-physics Company, Limited

Massachusetts Institute of Technology

Harvard College

Nycomed Amersham Sorin Srl

Cristina Bolzati

Fiorenzo Refosco

Francesco Tisato

Marina Porchia

Adriano Duatti

Licia Uccelli

Alessandra Boschi

Alessandro Maiocchi

Alan L Davison

Alun G Jones

Matthias Friebe

Simona Ghiani

Ashfaq Mahmood

Shinji Tokunaga

Rodolfo Franceschini

Stefania Agostini

Mario Cavazza-Ceccato

Barbara Spolaore

Nicola Salvarese

The present invention relates to a labeling procedure for the incorporation, in mild reaction conditions, of sensitive and thermosensitive targeting molecules into a [99m Tc(N)(PNP)]-based compound suitable for a kit formulation.

Method for labeling of sensitive and thermosensitive targeting biomolecules with technetium based compounds

A bisphosphonoamine compound represented by the following formula (I): wherein R1, R2, R3, R4 and R5 are independently an alkyl group having 1 to 6 carbon atoms, and n is an integer of 1 to 6, is extremely useful as an intermediate for preparing a technetium nitride complex for radiodiagnostic imaging. 

Intermediate compound of technetium nitride complex for radiodiagnostic imaging

The present invention provides radioactive metal heterocomplexes of formula (I): [(Me=N&#x2014;R)LL]+Zwherein Me, R, LLand Zhave the meanings indicated in the description. The complexes include a trivalent radioactive metal-imido group, typically a technetium-or rhenium-imido group, strongly stabilized by the presence of an ancillary tridentate hetero-diphosphine ligand L, which allows the formation of substitution-inert [(Me=N&#x2014;R)L] moieties. Such moieties are fixed in an intermediate [(Me=N&#x2014;R)YL)]+ compound which contains two labile, cispositioned, Y ligands, where Y is preferably an halide group. The latter are easily replaced by a bidentate ligand Lto give the final [(Me=N&#x2014;R)LL]+ Zheterocomplexes. The complexes of the invention are useful for the preparation of radiopharmaceuticals: in fact, a bioactive fragment which confers biological target-seeking properties can be introduced either on the Lframework or the imido R group.

Radioactive transition metal-imido hetero-diphosphine complexes, their preparation and radiopharmaceutical compositions thereof

A radiopharmaceutical for diagnostic imaging containing as an active ingredient a technetium-99m nitride heterocomplex comprising technetium-99m nitride and two different ligands coordinated therewith, i.e., a bisphosphinoamine compound as a &#x3c0; electron acceptor and a bidentate ligand as a &#x3c0; electron donor and represented by the following formula (I): [Tc(N)(PNP)(XY)](I)whereinTc(N) is technetium-99m nitride, PNP is a bisphosphinoamine compound and XY is a bidentate ligand, is markedly accumulated in heart and adrenal glands and hence is useful for radiodiagnostic imaging of heart and adrenal glands.

Radiopharmaceutical for diagnostic imaging containing a technetium-99m nitride heterocomplex

The present invention provides radioactive metal heterocomplexes of formula (I): [(Me&#x2550;N&#x2014;R)LL]+Z (I), wherein Me, R, LLand Zhave the meanings indicated in the description. The complexes include a trivalent radioactive metal-imido group, typically a technetium- or rhenium-imido group, strongly stabilized by the presence of an ancillary tridentate hetero-diphosphine ligand L, which allows the formation of substitution-inert [(Me&#x2550;N&#x2014;R)L] moieties. Such moieties are fixed in an intermediate [(Me&#x2550;N&#x2014;R)YL)]compound which contains two labile, cispositioned, Y ligands, where Y is preferably an halide group. The latter are easily replaced by a bidentate ligand Lto give the final [(Me&#x2550;N&#x2014;R)LL]Zheterocomplexes. The complexes of the invention are useful for the preparation of radiopharmaceuticals: in fact, a bioactive fragment which confers biological target-seeking properties can be introduced either on the Lframework or the imido R group.

The present invention relates to compounds and related technetium and rhenium complexes thereof which are suitable for imaging or therapeutic treatment of tumors, e.g., carcinomas, melanomas and other tumors. In another embodiment, the invention relates to methods of imaging tumors using radiolabeled metal complexes. Preferred radiolabeled complexes for imaging tumors include technetium and rhenium complexes. The high tumor uptake and significant tumor/nontumor ratios of the technetium complexes of the invention indicate that such small technetium-99m-based molecular probes can be developed as in-vivo diagnostic agents for melanoma and its metastases. In yet another embodiment, the invention relates to methods of treatment of tumors using a radiolabeled metal complex as a radiopharmaceutical agent to treat the tumor.

Small technetium-99m and rhenium labeled agents and methods for imaging tumors

Radioactive transition metal nitride heterocomplex

Method for the reduction of oxygenated compounds of rhenium or technetium

Growing community of inventors

Jolanda di Savoia, Italy

Cristina Bolzati