American Association for Cancer Research
10780432ccr133405-sup-ccr-13-3405figs1-4.pdf (301.91 kB)

Supplementary Figures 1 - 4 from A High-Affinity, High-Stability Photoacoustic Agent for Imaging Gastrin-Releasing Peptide Receptor in Prostate Cancer

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journal contribution
posted on 2023-03-31, 18:17 authored by Jelena Levi, Ataya Sathirachinda, Sanjiv S. Gambhir

PDF file - 300KB, Contains information about the dyes tested and characterization of the imaging agents. Figure S1. Dye Selection. The table lists all the dyes tested with their molecular weight, maximum excitation and emission wavelengths, extinction coefficient and quantum yield. Figure S2. AA3G-740 MALDI spectrum. Figure S3. Cell binding studies. A) Binding of AA3G-740 to PC3 cells was blocked by bombesin in a dose dependent manner. B) LNCaP cells showed minimal binding. At high concentration (30pmol) cell fluorescence was of a similar level as the one corresponding to non-specific binding in PC3 cells Figure S4. Blood lifetime. Very low amount of the agent was at 60 minutes post-injection suggesting short blood lifetime.



Purpose: To evaluate the utility of targeted photoacoustic imaging (PAI) in providing molecular information to complement intrinsic functional and anatomical details of the vasculature within prostate lesion.Experimental Design: We developed a PAI agent, AA3G-740, that targets gastrin-releasing peptide receptor (GRPR), found to be highly overexpressed in prostate cancer. The binding specificity of the agent was evaluated in human prostate cancer cell lines, PC3 and LNCaP, and antagonist properties determined by cell internalization and intracellular calcium mobilization studies. The imaging sensitivity was assessed for the agent itself and for the PC3 cells labeled with agent. The in vivo stability of the agent was determined in human plasma and in the blood of living mice. The in vivo binding of the agent was evaluated in PC3 prostate tumor models in mice, and was validated ex vivo by optical imaging.Results: AA3G-740 demonstrated strong and specific binding to GRPR. The sensitivity of detection in vitro indicated suitability of the agent to image very small lesions. In mice, the agent was able to bind to GRPR even in poorly vascularized tumors leading to nearly 2-fold difference in photoacoustic signal relative to the control agent.Conclusions: The ability to image both vasculature and molecular profile outside the blood vessels gives molecular PAI a unique advantage over currently used imaging techniques. The imaging method presented here can find application both in diagnosis and in image-guided biopsy. Clin Cancer Res; 20(14); 3721–9. ©2014 AACR.

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