title: Continuous sensing of tumor-targeted molecular probes with a vertical cavity surface emitting laser-based biosensor.
abstract: Molecular optical imaging is a widespread technique for interrogating molecular events in living subjects. However, current approaches preclude long-term, continuous measurements in awake, mobile subjects, a strategy crucial in several medical conditions. Consequently, we designed a novel, lightweight miniature biosensor for in vivo continuous optical sensing. The biosensor contains an enclosed vertical-cavity surface-emitting semiconductor laser and an adjacent pair of near-infrared optically filtered detectors. We employed two sensors (dual sensing) to simultaneously interrogate normal and diseased tumor sites. Having established the sensors are precise with phantom and in vivo studies, we performed dual, continuous sensing in tumor (human glioblastoma cells) bearing mice using the targeted molecular probe cRGD-Cy5.5, which targets αVβ3 cell surface integrins in both tumor neovasculature and tumor. The sensors capture the dynamic time-activity curve of the targeted molecular probe. The average tumor to background ratio after signal calibration for cRGD-Cy5.5 injection is approximately 2.43±0.95 at 1 h and 3.64±1.38 at 2 h (N=5 mice), consistent with data obtained with a cooled charge coupled device camera. We conclude that our novel, portable, precise biosensor can be used to evaluate both kinetics and steady state levels of molecular probes in various disease applications.
authors.affiliation: Stanford University, Molecular Imaging Program at Stanford, Division of Nuclear Medicine, Department of Radiology, James H. Clark Center, 318 Campus Drive, E153, Stanford, California 94305, USA.
authors.forename: Natesh
authors.initials: N
authors.lastname: Parashurama
authors.forename: Thomas D
authors.initials: TD
authors.lastname: O'Sullivan
authors.forename: Adam
authors.initials: A
authors.lastname: De La Zerda
authors.forename: Pascale
authors.initials: P
authors.lastname: El Kalassi
authors.forename: Seongjae
authors.initials: S
authors.lastname: Cho
authors.forename: Hongguang
authors.initials: H
authors.lastname: Liu
authors.forename: Robert
authors.initials: R
authors.lastname: Teed
authors.forename: Hart
authors.initials: H
authors.lastname: Levy
authors.forename: Jarrett
authors.initials: J
authors.lastname: Rosenberg
authors.forename: Zhen
authors.initials: Z
authors.lastname: Cheng
authors.forename: Ofer
authors.initials: O
authors.lastname: Levi
authors.forename: James S
authors.initials: JS
authors.lastname: Harris
authors.forename: Sanjiv S
authors.initials: SS
authors.lastname: Gambhir
mesh_terms: D000818:Animals; D015374:Biosensing Techniques / Q000295:instrumentation* / Q000379:methods; D002232:Carbocyanines; D045744:Cell Line, Tumor; D005260:Female; D005909:Glioblastoma / Q000175:diagnosis; D006801:Humans; D054023:Lasers, Semiconductor; D051379:Mice; D008819:Mice, Nude; D057054:Molecular Imaging / Q000295:instrumentation* / Q000379:methods; D015336:Molecular Probe Techniques; D015335:Molecular Probes; D055620:Optical Phenomena; D010456:Peptides, Cyclic; D019047:Phantoms, Imaging; D015203:Reproducibility of Results
chemical_list: C098793:CY5.5 cyanine dye; D002232:Carbocyanines; D015335:Molecular Probes; D010456:Peptides, Cyclic; C507169:cyclic arginine-glycine-aspartic acid peptide