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Molecular Assembly of Multifunctional 99m Tc Radiopharmaceuticals Using “Clickable” Amino Acid Derivatives
Author(s) -
Mindt Thomas L.,
Struthers Harriet,
Spingler Bernhard,
Brans Luc,
Tourwé Dirk,
GarcíaGarayoa Elisa,
Schibli Roger
Publication year - 2010
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201000342
Subject(s) - conjugate , click chemistry , chemistry , combinatorial chemistry , peptide , molecular imaging , in vivo , bombesin , cycloaddition , alkyne , biochemistry , receptor , catalysis , mathematical analysis , mathematics , microbiology and biotechnology , neuropeptide , biology
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 99m 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 99m 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 99m Tc‐based radiopharmaceuticals with significant potential for a multitude of applications.