JAA-F11 Anti-Thomsen-Friedenreich Antigen Targeted Imaging for Lung Cancer Differential Diagnosis

Lung cancer is the leading cancer killer in worldwideThe outcome of a lung cancer diagnosis is often bleakwith theyear survival rate for someone diagnosed with stagesmall cell lung cancerSCLCatdecreasing to onlyat stage IVFor non small cell lung cancersNSCLCtheyear survival rate of stage I iswhich decreases to onlyat stage IVAn earlier diagnosis will vastly improve survivalChest x rays and CT scans find overmillion pulmonary nodules of indeterminate significance annually in the U SAlthough most of these nodules are benigna missed early lung cancer diagnosis dramatically effects survival outcomesso these nodules cannot be dismissed without further scrutinyCurrentlythis is by usingFfluorodeoxyglucose positron emission tomographyF FDG PETdynamic contrast enhanced computer tomographyor biopsySinceF FDG accumulates in regions with high metabolic ratesinfectioninflammation and cancer can all cause a positive resultThushigher specificity as well as sensitivity are desired for diagnostic imagingThis Phaseproposal utilizes PET imaging in animal models to determine if hJAA Four patented highly specific humanized antibody to the tumor associated Thomsen Friedenreich antigenTF Agcan achieve higher sensitivity and specificity for detection of lung cancer without the confounding detection of inflammationImmunohistochemical analysis indicates that JAA Freacts withof human lung cancersboth NSCLC and SCLCand other carcinomas but not specifically with normal tissuesUse of hJAA Fimaging will be an innovative technology to differentially detect lung cancerwhere biomarker specific antibodies aren t currently usedSuccessful completion of the proposed preclinical aims will support the future clinical application ofI hJAA Fin the differential diagnosis of patients with lung cancerto distinguish non malignant causes of positiveF FDG PETimages from those associated with malignant tumorsAimwill conduct in vivo biological specificity analysis using microPET tumor localization withFFDG andI hJAA Fimaging and tissue biodistribution ofI hJAA Fin orthotopic and non orthotopic murine xenograft models of human lung cancer as well as a syngeneic breast cancer mouse model that develops metastatic tumors in the lungand healthy controlsAimwill conduct these studies in an influenza induced mouse lung inflammation modelAimwill assess dosimetryfalse negative and false positive results and clearance rates ofF FDG andI hJAA Fusing imagingbiodistribution data and histopathology analysis of lung tissues from the mice in above Aimsattodays after administration ofI hJAA FSuccessful SBIR Phase I studies will be followed by an SBIR Phase II study optimizing the isotope and linkage for patient use and performing pharmacologic characterizationsThese datacoupled with toxicology studies and cGMP antibody produced in our recent partnership with the NCI Experimental Therapeutics ProgramNExTwill allow Clinical Phase I Radiopharmaceutical Diagnostic Drug testing with radiolabeled hJAA FLung cancer is the leading cancer killer in the U Sand worldwideand although new treatments are providing some improvement to survival ratesearlier clinical diagnosis will vastly improve survivalChest x ray and CT scans can aid in this earlier diagnosisbut these methods are plagued with findings of indeterminate lesions wherein inflammatory lesions due to infection are difficult to differentiate from cancerWe hypothesize that the tumor specific biomarker antibodyhJAA Fwhich reacts withof all lung cancer typescan be radiolabeled and used in PET imaging to differentiate pulmonary tumors from inflammationand that this will allow earlier treatment of cancer patients and less invasive analysis for patients with inflammation due to infection