A new near-infrared absorption and fluorescent probe based on bombesin for molecular imaging

Naresh Kujala; Huifang Zhai; Charles Smith; Adam Prasanphanich; Gary Sieckman; Timothy Hoffman; Wynn Volkert; Lixin Ma; Ping Yu

doi:10.1117/12.809632

20 February 2009 A new near-infrared absorption and fluorescent probe based on bombesin for molecular imaging

Naresh Kujala, Huifang Zhai, Charles Smith, Adam Prasanphanich, Gary Sieckman, Timothy Hoffman, Wynn Volkert, Lixin Ma, Ping Yu

Author Affiliations +

Proceedings Volume 7190, Reporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications; 719010 (2009) https://doi.org/10.1117/12.809632
Event: SPIE BiOS, 2009, San Jose, California, United States

Abstract

We have developed a series of new dye bombesin conjugates for site-specific absorption and fluorescence imaging of human prostate and breast cancers. Bombesin (BBN), an amphibian analog to the endogenous ligand, binds to the gastrin releasing peptide (GRP) receptors with high specificity and affinity. Previously, we developed an Alexa Fluor 680-GGG-BBN peptide conjugate which demonstrated high binding affinity and specificity for breast cancer cells in the in vitro and in vivo tests (Ref: Ma et al., Molecular Imaging, vol. 6, no. 3, 2007: 171-180). This probe can not be used as an absorption probe in near-infrared imaging because its absorption peak is in the visible wavelength range. In addition, site specific longer wavelength fluorescent probe is desired for in vivo molecular imaging because long wavelength photons penetrate deeper into tissue. The new absorption and fluorescent probe we developed is based on the last eight-residues of BBN, -Q-W-A-V-G-H-L-M-(NH₂), and labeled with AlexaFluor750 through a chemical linker, beta-alanine. The new probe, Alexa Fluor 750-BetaAla-BBN(7-14)NH₂, exhibits optimal pharmacokinetics for specific targeting and optical imaging of the GRP receptor over-expressing cancer cells. Absorption spectrum has been measured and showed absorption peaks at 690nm, 720nm and 735nm. Fluorescent band is located at 755nm. In vitro and in vivo investigations have demonstrated the effectiveness of the new conjugates to specifically target human cancer cells overexpressing GRP receptors and tumor xenografts in severely compromised immunodeficient mouse model.

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Naresh Kujala, Huifang Zhai, Charles Smith, Adam Prasanphanich, Gary Sieckman, Timothy Hoffman, Wynn Volkert, Lixin Ma, and Ping Yu "A new near-infrared absorption and fluorescent probe based on bombesin for molecular imaging", Proc. SPIE 7190, Reporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications, 719010 (20 February 2009); https://doi.org/10.1117/12.809632

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