Current status of targeted microbubbles in diagnostic molecular imaging of pancreatic cancer

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is often associated with a poor prognosis due to silent onset, resistance to therapies, and rapid spreading. Most patients are ineligible for curable surgery as they present with advanced disease at the time of diagnosis. Present diagnostic methods relying on anatomical changes have various limitations including difficulty to discriminate between benign and malignant conditions, invasiveness, the ambiguity of imaging results, or the inability to detect molecular biomarkers of PDAC initiation and progression. Therefore, new imaging technologies with high sensitivity and specificity are critically needed for accurately detecting PDAC and noninvasively characterizing molecular features driving its pathogenesis. Contrast enhanced targeted ultrasound (CETUS) is an upcoming molecular imaging modality that specifically addresses these issues. Unlike anatomical imaging modalities such as CT and MRI, molecular imaging using CETUS is promising for early and accurate detection of PDAC. The use of molecularly targeted microbubbles that bind to neovascular targets can enhance the ultrasound signal specifically from malignant PDAC tissues. This review discusses the current state of diagnostic imaging modalities for pancreatic cancer and places a special focus on ultrasound targetedmicrobubble technology together with its clinical translatability for PDAC detection.

Purification of a Clinical Grade Recombinant Thy1-Single-Chain Variable Fragment for Molecular Imaging of Pancreatic Ductal Adenocarcinoma

“…37 Efforts have been made to develop molecular imaging probes capable of detecting early stage PDAC. 38 Here, we produced a clinically translatable Thy1-scFv conjugated-US contrast agent, MBThy1-scFv, and illustrated its potential for non-invasively enhancing US contrast between PDAC and normal pancreatic tissues in mice consistent with related findings. 24,39 Our probe, able to detect small foci in the pancreas (>2 mm), constitutes a promising translatable US molecular imaging agent.…”

Expression and purification of a native Thy1-single-chain variable fragment for use in molecular imaging

“…Given the low median survival rate (5-year survival rate < 9%) and the low percentage of PDAC patients qualifying for tumor resection (10–20%), the need for early screening methods is globally recognized 36 . Efforts have been made to develop molecular imaging probes capable of detecting early stage PDAC 37 . Here, we produced Thy1-scFv conjugated-US contrast agent, MB Thy1-scFv , and illustrated its potential for non-invasively enhancing USMI contrast between PDAC and normal pancreatic tissues in mice consistent with related findings 24 , 38 .…”

Nanodiscs: a versatile nanocarrier platform for cancer diagnosis and treatment

“…94 Cancer imaging, including fluorescent imaging, computed tomography (CT), MRI, transabdominal or endoscopic ultrasound imaging, and positron emission tomography (PET) imaging are often used for early-stage cancer detection. 95 Among these techniques, CT, MRI, and ultrasound imaging are anatomical imaging modalities. Fluorescent imaging and PET are molecular imaging techniques that complement anatomical imaging modalities by providing functional and molecular information.…”