Targeted Noninvasive Imaging of EGFR-Expressing Orthotopic Pancreatic Cancer Using Multispectral Optoacoustic Tomography

Abstract

Detection of orthotopic xenograft tumors is difficult due to poor spatial resolution and reduced image fidelity with traditional optical imaging modalities. In particular, light scattering and attenuation in tissue at depths beyond subcutaneous implantation hinder adequate visualization. We evaluate the use of multispectral optoacoustic tomography (MSOT) to detect upregulated epidermal growth factor (EGF) receptor in orthotopic pancreatic xenografts using a near-infrared (NIR) EGF-conjugated CF-750 fluorescent probe. MSOT is based on the photoacoustic effect and thus not limited by photon scattering, resulting in high-resolution tomographic images. Pancreatic tumor-bearing mice with luciferase-transduced S2VP10L tumors were intravenously injected with EGF-750 probe prior to MSOT imaging. We characterized probe specificity and bioactivity via immunoblotting, immunocytochemistry, and flow cytometric analysis. In vitro data along with optical bioluminescence/fluorescence imaging were used to validate acquired MSOT in vivo images of probe biodistribution. Indocyanine green dye was used as a non-specific control to define specificity of EGF-probe accumulation. Maximum accumulation occurred at six hours post-injection, demonstrating specific intra-tumoral probe uptake and minimal liver and kidney off-target accumulation. Optical bioluminescence and fluorescence imaging confirmed tumor-specific probe accumulation consistent with MSOT images. These studies demonstrate the utility of MSOT to obtain volumetric images of ligand probe biodistribution in vivo to detect orthotopic pancreatic tumor lesions through active targeting of EGF receptor.

Inflammatory stimuli promote growth and invasion of pancreatic cancer cells through NF-κB pathway dependent repression of PP2Ac

“…Orthotopic cell implantation was performed as previously described. 56 Cells (5 £ 10 6 ) in 100 ml Matrigel (Becton Dickinson) were injected into the body-tail of the pancreas of nude mice. One week after orthotopic implantation, the mice were randomized into 2 groups: control and DBTCtreated.…”

Targeted Molecular Imaging of Pancreatic Cancer with a Miniature Endoscope

“…For pancreatic cancer, current existing molecular imaging techniques include positron emission tomography (PET) [5][6][7][8], single-photon emission computed tomography (SPECT) [9,10], MRI with contrast agent enhancement (such as magnetic nanoparticles) [11][12][13][14][15], optical/fluorescence imaging [14,16,17], and photoacoustic imaging (PAI) [18][19][20]. PET and SPECT involve ionization radiation with the long half-life of radiotracers which limits the temporal resolution.…”

Targeting Acidity in Pancreatic Adenocarcinoma: Multispectral Optoacoustic Tomography Detects pH-Low Insertion Peptide Probes In Vivo

“…(7–10) These cell surface proteins are typically some type of specific molecular receptor such as epidermal growth factor receptor (EGFr). (9–10) Unfortunately, these surface receptors are frequently heterogeneously expressed among different patients, and will even vary among the clonal populations that comprise a single tumor. (11) Tumors are complex environments, where altered cellular signaling, genetic and epigenetic deregulations, and interactions with the microenvironment contribute to a constantly changing phenotype, including the expression of extracellular proteins.…”