Cover image for Vol. 11 Issue 10

Editorial Board Chairs: Antonello Mai, Rainer Metternich. Assoc. Editors: David Peralta, Scott Williams (Sr)

Impact Factor: 2.968

ISI Journal Citation Reports © Ranking: 2014: 19/59 (Chemistry Medicinal); 83/255 (Pharmacology & Pharmacy)

Online ISSN: 1860-7187

Associated Title(s): Angewandte Chemie International Edition, Chemistry - A European Journal, Chemistry – An Asian Journal, ChemBioChem, Medicinal Research Reviews, Molecular Informatics

October 06, 2010

VIP: Molecular Assembly of Multifunctional 99mTc Radiopharmaceuticals Using "Clickable" Amino Acid Derivatives

Thomas L. Mindt,* Harriet Struthers, Bernhard Spingler, Luc Brans, Dirk Tourwé, Elisa García-Garayoa, and Roger Schibli*

Radioactively labeled compounds are important for use as imaging probes or radiotherapeutic agents. Most radioisotopes with decay properties suitable for diagnosis and therapy are transition metals or elements that have metallic character. Therefore, bifunctional chelating agents are required for stable complexation of a given radionuclide and its attachment to targeted biomolecules of interest. Although radioconjugates hold vast potential, their preparation by conventional synthetic means is a big challenge. Therefore, new and efficient synthetic strategies for the controlled assembly of multifunctional radionuclide-containing conjugates are crucial.

Mindt, Schibli, et al. applied copper(I)-catalyzed alkyne--azide cycloaddition (CuAAC, click chemistry) toward the efficient assembly of conjugates containing a 99mTc-based SPECT probe and two different biochemical entities. By starting from azide-functionalized biomolecules and readily available alkyne pro-chelators derived from amino acids, the team assembled multifunctional conjugates by convenient one-pot procedures without the need for protecting groups. They applied this methodology to the preparation of a 99mTc-labeled conjugate comprising a tumor-targeting peptide sequence (bombesin(7--14)) and a low-molecular-weight albumin binder (a pharmacological modifier that prolongs the conjugate's blood circulation lifetime).

The possibility of selectively combining two different groups with biological function and a metal chelating system in a single step is a very attractive feature for the development of metallic radiotracers and opens numerous applications with great potential, including the design of radiopharmaceuticals with improved biological characteristics, multimodality imaging probes, bivalent or bi-specific targeting agents, and conjugates useful for combination therapies.

Received August 11, 2010; published online October 4, 2010, DOI: 10.1002/cmdc.201000342.

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