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Development of new macrocyclic bifunctional chelators for metalloradiopharmaceuticals

Instituto de Tecnologia Química e Biológica
Project classification

Scientific area

1.4 Chemical sciences


Organic chemistry

Project description

Project title

Development of new macrocyclic bifunctional chelators for metalloradiopharmaceuticals

Scientific Coordinator's name:

Rita Delgado

Scientific Coordinator's e-mail:

Principal R&D Unit:

Instituto de Tecnologia Química e Biológica

Other R&D Units involved in the project:


Project keyword(s)

Bifuncional chelators; cross-bridged tetraaza derivatives; thermodynamic constants; kinetics studies; metalloradiopharmaceutic drug

Short abstract and comments

Metalloradiopharmaceuticals for diagnosis and treatment of tumours are currently a field of intense research. This type of drug is composed of a radiolabelled conjugate that binds to specific receptors that are overexpressed in certain regions or organs in the body. The fragment of the conjugate that encapsulates the radiometal is a bifunctional chelator (BFC) that also presents a suitable functionality for the covalent binding to a carrier agent. The design of new BFCs suitable for diagnostic and therapeutic drugs, the study of their chemical and biological properties, are the goals of the present project. The metallic radionuclides chosen are 64/67Cu, 67/68Ga, 111In, 153Sm, 166Ho, and 177Lu, which are some of the most used nowadays. For these applications it is required that the radiometal chelates preserve their chemical integrity during storage, transport, and residence time in the patient body. This requires a strong binding of the radionuclide by the chelator, especially if considering that the concentration of competing biological ligands is thousand to hundred thousand times higher than that of BFCs. Therefore, the in vivo stability of radiometal-BFC conjugates depends mainly on their kinetic inertness and thermodynamic stability. In order to enhance the understanding of the main features that control the chemical and biological side effects of metalloradiopharmaceuticals, and to develop new drugs for tumour radiodiagnosis or radiotherapy, the synthesis of a new family of 12- to 14-membered cross-bridged tetraaza macrocycles N-substituted containing carboxylate, amide and/or phosphonate groups will be undertaken. The macrocyclic backbone of this family of chelators forms a tridimensional and rigid cavity appropriate to accommodate the specific metal ion by the direct binding of the four nitrogen donor atoms of the amines, together with the additional coordination of the four oxygen atoms of the appending arms, consequently being capable of fulfilling the demands of all the envisaged metal ions. The cavity dimension can be modulated by the size of the bridge, and biomolecules can be attached via a group in one of the arms. The compounds forming complexes with very high stability constants and kinetic inertness will be selected for biological studies using the radioisotopes, in order to establish their radiochemical purity and pharmacokinetics.

Potential uses/indications

Development of radiopharmaceutical drugs for diagnostic and therapy. Knowledge: synthesis; thermodynamic and kinetic studies.



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Grant number (QREN, FP7, Eureka, etc)


Last edited on

2012-12-05 15:58:16

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