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111In-Labeled multifunctional single-attachment-point reagent-c[RGDfK].


Shan L1.


Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013.
2012 Jul 13 [updated 2012 Aug 21].

Author information

National Center for Biotechnology Information, NLM, NIH


111In-Labeled multifunctional single-attachment-point reagent (MSAP)-c[RGDfK], abbreviated as 111In-MSAP-RGD, is a multimodality imaging agent synthesized by Bunschoten et al. for imaging tumors by targeting integrin αvβ3 (1). MSAP is a conjugate that consists of a Cy5.5 derivative (CyAL-5.5b) and a chelate of diethylenetriamine pentaacetic acid (DTPA). CyAL-5.5b is a symmetric, monofunctional pentamethine carbocyanine fluorophore with an alkyl carboxylic acid functional group (λex = 674 nm, λem = 693 nm). Angiogenesis is a process of neovascular development and growth from pre-existing vessels. Unlike the normal blood vessel system, the neovasculature is chaotic and irregular in tumors with abnormal expression of diverse vascular surface biomarkers. These biomarkers have fewer kinetic compartments that must be crossed for intravenously administered agents to reach them (2, 3). Integrin αvβ3 is one of these biomarkers and has been intensively investigated as a target for imaging and antiangiogenic therapy. Integrin αvβ3 is minimally expressed in normal blood vessels but is significantly overexpressed in newly sprouting vasculature in tumors (4, 5). For targeting purposes, small peptides have been widely used, and the representative peptides include arginine-glycine-aspartic acid (RGD), asparagine-glycine-arginine, histidine-glycine-phenylalanine, and arginine-arginine-leucine (3). The RGD tripeptide sequence is an adhesive protein recognition site, presenting in the extracellular matrix and blood. Integrin αvβ3 binds extracellular matrix proteins through the exposed RGD tripeptide sequence. Although both linear and cyclic RGD peptides have been proven to be valuable in imaging tumor neovasculature, the cyclic form appears superior to the linear form in the aspect of pharmacokinetics because cyclic peptides are trapped in the active conformation and thus are more resistant to proteolysis in vivo (6). To optimize the pharmacokinetic behavior of RGD peptides, the peptides have been further modified with the introduction of sugar moieties or by coupling with a chelating agent or polyethylene glycol. In general, RGD peptides are less selective (binding with 8 of the 24 integrins), degrade rapidly in vivo, and have a relatively low binding affinity (3, 7). Beside peptides, several classes of peptidomimetic antagonists have also been synthesized, which consist of a rigid core scaffold bearing basic and acidic groups that mimic the guanidine and carboxylate groups of the RGD sequence (8). Peptidomimetic antagonist-conjugated magnetic nanoparticles have been demonstrated to delineate very small regions (~30 mm3) of angiogenesis and enable phenotyping and staging of early tumors in a clinical setting. Improving the binding affinity and increasing the circulation time of peptides are still the key topics for successful imaging of angiogenesis. Bunschoten et al. synthesized 111In-MSAP-RGD by modifying the cyclic RGD peptides with DTPA and labeling them with a Cy5.5 derivative (CyAL-5.5b) and 111In (1). This agent was tested for its effectiveness for imaging tumors, identifying lymph node metastasis, and visualizing tumor margins for surgery (1). This chapter summarizes the data obtained with 111In-MSAP-RGD.

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