Non-destructive and instant intraoperative margin assessment of high grade dysplasia and cancer of the cervix and vulva

PROJECT SUMMARY ABSTRACT This resubmission seeks to develop and establish our optical imaging agentPARPi FLas a new drug for margin assessment of high grade dysplasia and cancer of the cervix and vulvarThis new technology will allow non destructive and instant intraoperative margin assessment of surgically excised vulvar and cervical dysplasia specimens and early vulvar and cervical cancersSo farwell established screening technologiessuch as the Pap smearhave helped to reduce the mortality rate for cervical cancer byover the last four decades in the United StatesPositive Pap smears usually lead to interventions such as a loop electrosurgical procedureLEEPThese LEEPshowevercan only rely on simple acetic acid to generate a visual contrast between healthy and cancerous tissueIntuitivelythis contrast is frequently weak and unreliableresulting in imperfect interventions that ultimately lead to cancer recurrenceRepeated LEEPs also result in cervical scarringincreasing the risk of preterm delivery a significant issue for the LEEP patient population of childbearing ageIn the current resubmissionSummit Biomedical ImagingSBIwill use its unique drugwhich is currently being evaluated in a phase I clinical trial as an intraoperative imaging agent for oral cancer at Memorial Sloan Kettering Cancer CenterMSKto non invasively and non destructively determine if the margins of cervical cone specimenscervical loop electrical excisionsand vulvar excisions are negative or positive at the time of the surgical procedureThis project will serve as a proof of principle study to optimize staining for identification of diseasevalidate methodologyand choose the best imaging microscope setup for margin detectionWe will also conduct a blinded margin assessment studyoverseen by the Department of Epidemiology andampBiostatistics at MSKwhere we will determine positive predictive valuesPPVand negative predictive valuesNPVof our technologyFor this studywe have brought together an interdisciplinary team of experts to facilitate the translation of this new biomedical imaging technology to the clinicDrChristian BrandCEO and molecular imaging expertwill manage the efforts at SBIThe MSK research team will comprise DrThomas Reinerprobe development and laboratory analyticsDrElizabeth Jewellgynecological surgeonand DrSnehal Pateloral cancer surgeon and intra operative imaging expertTogetherthey form an ideal team to pursue this novel research avenue and represent expertise from a wide variety of disciplinesIf successfulthis study will form the basis of an SBIR phase II proposalin which SBI will focus on clinical translation by initiating a phase I II clinical study in concert with MSK PROJECT NARRATIVE This resubmission describes the evaluation of a diagnostic tool for margin assessment of high grade dysplasia and cancer of the cervix and vulvaTargeting the overexpression of PARPSBIandapos s imaging agentPARPiFLwill be used as a non invasive and non destructive intraoperative imaging agentThe main objectives of our proposal are to optimize staining of diseasevalidate methodologyand select the best imaging microscope setup for margin detection in fresh human biospecimens of cervical high grade dysplasia and cancer of cervix and vulva