An clinical imaging platform for the intraoperative assessment of marginal tissue after BCS resection using in-vivo topical application of a cathepsin-targeted molecular probe

Project Summary AbstractBreast cancer is the most common cancer in womenwith a projectedcasesand more thandeathsin the US duringDue to better screening techniques cancers are caught earlier andof patients are candidates for breast conserving surgeryBCSto remove the cancerBCS is cosmetically preferable to the alternativemastectomyand long term survival rates are equivalentThe success of BCS is assessed post operatively by pathologyThe status of the microscopic margins of excision of the lumpectomy specimen is still the most important prognostic and risk factor for local recurrenceA positive margin indicates that invasive carcinoma or ductal carcinoma in situ is touching a tissue edge of a lumpectomy specimenAmong patients treated by BCS and radiation therapypositive margins are associated with afold increase in the risk of local recurrence when compared with negative marginsA finding of positive margins is estimated to occur betweentoof the timerequiring patients to return for further treatment often associated with poorer cosmetic results and increases in local and distant recurrence of the diseaseCurrent pathology methods only assess aboutofof the entire volume of the removed specimenA consequence of margin undersampling is that local recurrence occurs inof patients with pathologically clean marginssuggesting that one or more regions of tumor had not been sampled during pathological analysis resulting in tumor remaining in the patientIn additionthere is still no universal agreement among breast surgeons on what constitutes an adequate negative margin for patients undergoing BCSTogether these data demonstrate the unmet clinical need for technologies that rapidly and globally identify cancerous tissues in the surgical cavity and can be used to guide their surgical resections during the procedureMolecular imaging guided resections of tumors during surgeries are now being developedHowevermost approaches employ IV administration of optical imaging agentswhich require hours or days to highlight tumor tissuesMoreoverinfiltrating cancer cells in tissues surrounding the main mass may not have developed a vasculature and likely would not be identified using injected agentsFinallyilluminating the entire cancer mass may create a high background signal from tumor that is notat the marginof the lumpectomyExploiting increased protease expression at the edge of breast cancers we introduce the novel concept of in vivo topical administration of quenched fluorescent molecular imaging probes to identify cancer that may remain in the surgical cavity after standard of care resectionBuilding on years of preclinical ex vivo studiesthis Phase I project seeks to develop preliminary performance data for in vivo topical applicationIf this technology can be successfully translated to the clinicit has the potential to reduce re excisions as well as the false negative rate from pathology undersamplingwith a consequent savings in healthcare costs andenhancement in patient life quality Project NarrativeThe purpose of this Phase I project is to perform studies necessary for the eventual clinical translation of an integrated imaging solution for the intraoperativereal time detection of residual cancer on or near the surface of the surgical cavity after standard of care Breast Conservation SurgeryBCS orlumpectomyConsisting of a quenchedfluorescent probe applied topically in vivo to the surgical cavityand an FDA approved imaging instrumentthe PDE neoHamamatsu Photonicsthis technology has the potential to reduce repeat procedure rates due to incomplete resectioncurrently betweenandThe finalapproved platform will have the potential to significantly reduce healthcare costs due to repeat surgerieswith associated reductions in risks of mortality morbidity and enhancement in patient quality of life