64Cu-Labeled 4-((8-amino-3,6,10,13,16,19-hexaazabicyclo [6.6.6] icosane-1-ylamino)methyl)benzoic acid (AmBaSar) conjugated to cyclic arginine-glycine-aspartic acid (RGD) peptide

Excerpt

The integrin α_vβ₃ receptor is one of several known biomarkers of cancerous tumor angiogenesis (1) and metastasis (2). Therefore, molecular imaging (MI) of integrin α_vβ₃ receptor expression in tumors is considered to be useful for the detection of malignant tumors and the development of an individualized treatment and monitoring regimen for the patient (3). Ligands such as vitronectin, fibronectin, etc., which interact with integrins, are known to bind these receptors through an Arg-Gly-Asp (RGD) epitope. Consequently, many MI probes used for the detection and quantification of integrins with positron emission tomography (PET) or multimodal imaging are based on an RGD motif containing a peptide or its derivative and are labeled with ¹⁸F or are conjugated to a chelator for the binding of ⁶⁴Cu (3, 4). In this regard, ⁶⁴Cu can be considered to be a more suitable nuclide than ¹⁸F (half-life, ~110 min) for the development of a MI probe that can be used to detect integrin α_vβ₃ receptors because of its longer half-life (12.7 h) because a longer circulation time can be necessary for the penetration of dense tumors (5). Recently a cage-like bifunctional chelator, 4-((8-amino-3,6,10,13,16,19-hexaazabicyclo [6.6.6] icosane-1-ylamino)methyl)benzoic acid (AmBaSar) was developed and conjugated to RGD for labeling with ⁶⁴Cu ([⁶⁴Cu]-AmBaSar-RGD) (3). Subsequently, Cai et al. evaluated the biodistribution of [⁶⁴Cu]-AmBaSar-RGD and its effectiveness in the detection of tumors expressing integrin α_vβ₃ receptors in mice bearing U-87MG cell tumors, which express integrin α_vβ₃ receptors (3).