Universal Molecular Scaffold for Facile Construction of Multivalent and Multimodal Imaging Probes

Abstract

Multivalent and multimodal imaging probes are rapidly emerging as powerful chemical tools for visualizing various biochemical processes. Herein, we described a bifunctional chelator (BFC)-based scaffold that can be used to construct such promising probes concisely. Compared to other reported similar scaffolds, this new BFC scaffold demonstrated two major advantages: (1) significantly simplified synthesis due to the use of this new BFC that can serve as chelator and linker simultaneously; (2) highly effcient synthesis rendered by using either click chemistry and/or total solid-phase synthesis. In addition, the versatile utility of this molecular scaffold has been demonstrated by constructing several multivalent/multimodal imaging probes labeled with various radioisotopes, and the resulting radiotracers demonstrated substantially improved in vivo performance compared to the two individual monomeric counterparts.

Rational design of a multifunctional molecular dye for dual-modal NIR-II/photoacoustic imaging and photothermal therapy

“…[9][10][11][12][13] However, the widespread applications of such promising probes in biomedicine are heavily hampered as introducing different functional molecules into the molecular platform usually involves abundant and complex chemistry including multiple synthetic steps, tedious chromatographic separations, and issues of chemo-selectivity. [14][15][16][17] Hence, continuous efforts should be made to design simple uorophores with intrinsic multifunctional ability, which have high signicance and direct impact on the eld of uorescence imaging and biomedicine. 18,19 Over the past several years, uorescence based imaging in the second near-infrared channel (NIR-II, 1000-1700 nm) has gained attention for its prominent merits and surpasses the conventional visible/NIR-I channels (700-900 nm) in terms of lower tissue scattering and minimal auto-uorescence, thus leading to signicant advances in imaging qualities including image depth and spatiotemporal resolution.…”

Development of Dual Receptor Enhanced Pre‐Targeting Strategy—A Novel Promising Technology for Immuno‐Positron Emission Tomography Imaging

“…Another chemical tool MeTz‐NOTA‐RGD was prepared using our previously developed bifunctional NOTA chelator [ 33 ] via a multiple step synthetic scheme (Scheme S1, Supporting Information). Briefly, using commercially available NH 2 ‐PEG 3 ‐NH(Boc), N 3 ‐NOTA(tBu)‐COOH was first converted to N 3 ‐NOTA(tBu)‐PEG 3 ‐NH(Boc), which was then conjugated with RGD‐PEG 4 ‐BCN to give RGD‐PEG 4 ‐NOTA(tBu)‐PEG 3 ‐NH(Boc).…”

Dual-Targeted Molecular Imaging of Cancer

“…was developed by Zeng's group (8). Unlike (HBED-CC) TFP 2 , which possesses two identical reactive groups, N 3 -NO t B 2 contains two different reactive groups including an N 3 group for click chemistry and a COOH group for amide coupling, offering selectivity for conjugation with two different peptides.…”

“…Another recent example is the RGD-AE105 heterodimer that was prepared by Gai et al, using the BFC framework N 3 -NO t B 2 (8). The prepared RGD-AE105 tracer targets both the integrin a v b 3 and the urokinase-type plasminogen activator receptor simultaneously.…”