Purpose: Pancreatic cancer is among the most aggressive malignancies and is rarely discovered early. However, pancreatic 'incidentalomas', particularly cysts, are frequently identified in asymptomatic patients through anatomical imaging for unrelated causes. Accurate determination of the malignant potential of cystic lesions could lead to life-saving surgery or spare patients with indolent disease undue risk. Current risk assessment of pancreatic cysts requires invasive sampling, with attendant morbidity and sampling errors. Here, we sought to identify imaging biomarkers of high-risk pancreatic cancer precursor lesions. Experimental Design: Translocator protein (TSPO) expression, which is associated with cholesterol metabolism, was evaluated in pre-malignant and pancreatic cancer lesions from human and genetically engineered mouse (GEM) tissues. In vivo imaging was performed with [18F]V-1008, a TSPO-targeted positron emission tomography (PET) agent, in two GEM models. For image-guided surgery (IGS), V-1520, a TSPO ligand for near-infrared optical imaging based upon the V-1008 pharmacophore, was developed and evaluated. Results: TSPO was highly expressed in human and murine pancreatic cancer. Notably, TSPO expression was associated with high-grade, pre-malignant intraductal papillary mucinous neoplasms (IPMNs) and pancreatic intraepithelial neoplasia (PanIN) lesions. In GEM models, [18F]V-1008 exhibited robust uptake in early pancreatic cancer, detectable by PET. Furthermore, V-1520 localized to pre-malignant pancreatic lesions and advanced tumors enabling real-time IGS. Conclusions: We anticipate that combined TSPO PET/IGS represents a translational approach for precision pancreatic cancer care through discrimination of high-risk indeterminate lesions and actionable surgery.
Τρίτη 15 Σεπτεμβρίου 2020
TSPO-targeted PET and Optical Probes for the Detection and Localization of Pre-Malignant and Malignant Pancreatic Lesions
TSPO-targeted PET and Optical Probes for the Detection and Localization of Pre-Malignant and Malignant Pancreatic Lesions:
Purpose: Pancreatic cancer is among the most aggressive malignancies and is rarely discovered early. However, pancreatic 'incidentalomas', particularly cysts, are frequently identified in asymptomatic patients through anatomical imaging for unrelated causes. Accurate determination of the malignant potential of cystic lesions could lead to life-saving surgery or spare patients with indolent disease undue risk. Current risk assessment of pancreatic cysts requires invasive sampling, with attendant morbidity and sampling errors. Here, we sought to identify imaging biomarkers of high-risk pancreatic cancer precursor lesions. Experimental Design: Translocator protein (TSPO) expression, which is associated with cholesterol metabolism, was evaluated in pre-malignant and pancreatic cancer lesions from human and genetically engineered mouse (GEM) tissues. In vivo imaging was performed with [18F]V-1008, a TSPO-targeted positron emission tomography (PET) agent, in two GEM models. For image-guided surgery (IGS), V-1520, a TSPO ligand for near-infrared optical imaging based upon the V-1008 pharmacophore, was developed and evaluated. Results: TSPO was highly expressed in human and murine pancreatic cancer. Notably, TSPO expression was associated with high-grade, pre-malignant intraductal papillary mucinous neoplasms (IPMNs) and pancreatic intraepithelial neoplasia (PanIN) lesions. In GEM models, [18F]V-1008 exhibited robust uptake in early pancreatic cancer, detectable by PET. Furthermore, V-1520 localized to pre-malignant pancreatic lesions and advanced tumors enabling real-time IGS. Conclusions: We anticipate that combined TSPO PET/IGS represents a translational approach for precision pancreatic cancer care through discrimination of high-risk indeterminate lesions and actionable surgery.
Purpose: Pancreatic cancer is among the most aggressive malignancies and is rarely discovered early. However, pancreatic 'incidentalomas', particularly cysts, are frequently identified in asymptomatic patients through anatomical imaging for unrelated causes. Accurate determination of the malignant potential of cystic lesions could lead to life-saving surgery or spare patients with indolent disease undue risk. Current risk assessment of pancreatic cysts requires invasive sampling, with attendant morbidity and sampling errors. Here, we sought to identify imaging biomarkers of high-risk pancreatic cancer precursor lesions. Experimental Design: Translocator protein (TSPO) expression, which is associated with cholesterol metabolism, was evaluated in pre-malignant and pancreatic cancer lesions from human and genetically engineered mouse (GEM) tissues. In vivo imaging was performed with [18F]V-1008, a TSPO-targeted positron emission tomography (PET) agent, in two GEM models. For image-guided surgery (IGS), V-1520, a TSPO ligand for near-infrared optical imaging based upon the V-1008 pharmacophore, was developed and evaluated. Results: TSPO was highly expressed in human and murine pancreatic cancer. Notably, TSPO expression was associated with high-grade, pre-malignant intraductal papillary mucinous neoplasms (IPMNs) and pancreatic intraepithelial neoplasia (PanIN) lesions. In GEM models, [18F]V-1008 exhibited robust uptake in early pancreatic cancer, detectable by PET. Furthermore, V-1520 localized to pre-malignant pancreatic lesions and advanced tumors enabling real-time IGS. Conclusions: We anticipate that combined TSPO PET/IGS represents a translational approach for precision pancreatic cancer care through discrimination of high-risk indeterminate lesions and actionable surgery.
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