Molecular assembly of multifunctional ⁹⁹(m)Tc radiopharmaceuticals using "clickable" amino acid derivatives.

Abstract

Synthetic strategies that enable the efficient and selective combination of different biologically active entities hold great promise for the development of multifunctional hybrid conjugates useful for biochemical and medical applications. Starting from side-chain-functionalized N(α)-propargyl lysine derivatives, conjugates containing a ⁹⁹(m)Tc-based imaging probe for SPECT and two different moieties (e.g., tumor-targeting vectors, pharmacological modifiers, affinity tags, or second imaging probes) can be assembled using the Cu(I)-catalyzed alkyne-azide cycloaddition in efficient one-pot protocols. This strategy was successfully applied to the preparation of a ⁹⁹(m)Tc-labeled conjugate comprising a tumor-targeting peptide sequence (bombesin(7-14)) and a low-molecular-weight albumin binder, a pharmacological modifier that prolongs the blood circulation time of the conjugate. Evaluation of the conjugate in vitro and in vivo provided promising results for its use as an imaging agent for the visualization of tumors positive for the gastrin-releasing peptide receptor. The methodology presented herein provides an attractive synthetic tool for the preparation of multifunctional ⁹⁹(m)Tc-based radiopharmaceuticals with significant potential for a multitude of applications.

• Authors: Thomas L Mindt, Harriet Struthers, Bernhard Spingler, Luc Brans, Dirk Tourwé, Elisa García-Garayoa, Roger Schibli
• Journal: ChemMedChem (ChemMedChem) Vol. 5 Issue 12 Pg. 2026-38 (Dec 03 2010) ISSN: 1860-7187 [Electronic] Germany
• PMID: 20922747 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Alkynes
• Amino Acids
• Azides
• Radiopharmaceuticals
• Technetium
• Copper
• Lysine
• Bombesin

Topics

• Alkynes (chemistry)
• Amino Acids (chemistry)
• Azides (chemistry)
• Bombesin (chemistry)
• Catalysis
• Cell Line, Tumor
• Click Chemistry
• Copper (chemistry)
• Crystallography, X-Ray
• Humans
• Lysine (chemistry)
• Molecular Conformation
• Radiopharmaceuticals (chemistry)
• Technetium (chemistry)
• Tomography, Emission-Computed, Single-Photon