A high-affinity, high-stability photoacoustic agent for imaging gastrin-releasing peptide receptor in prostate cancer.
OBJECTIVE
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.


METHODS
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.
Authors' Affiliations: Canary Center at Stanford for Cancer Early Detection; and Molecular Imaging Program at Stanford, Department of Radiology and Bio-X Program, Stanford University, Palo Alto, Stanford, California.
Jelena
J
Levi
Authors' Affiliations: Canary Center at Stanford for Cancer Early Detection; and Molecular Imaging Program at Stanford, Department of Radiology and Bio-X Program, Stanford University, Palo Alto, Stanford, California.
Ataya
A
Sathirachinda
Authors' Affiliations: Canary Center at Stanford for Cancer Early Detection; and Molecular Imaging Program at Stanford, Department of Radiology and Bio-X Program, Stanford University, Palo Alto, Stanford, California sgambhir@stanford.edu.
Sanjiv S
SS
Gambhir
D000818:Animals; D045744:Cell Line, Tumor; D003952:Diagnostic Imaging / Q000379:methods; D004355:Drug Stability; D006801:Humans; D008297:Male; D008819:Mice, Nude; D015335:Molecular Probes / Q000378:metabolism; D009368:Neoplasm Transplantation; D009842:Oligopeptides / Q000378:metabolism; D061088:Photoacoustic Techniques / Q000379:methods*; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D011485:Protein Binding; D018004:Receptors, Bombesin / Q000378:metabolism*
C000600928:AA3G-740; D015335:Molecular Probes; D009842:Oligopeptides; D018004:Receptors, Bombesin