Simple Summary: We have developed a formulation for an innovative, quenched, cathepsin-targeted, fluorescent molecular probe to enhance resection quality for several solid-tumor cancers. Unlike... Show moreSimple Summary: We have developed a formulation for an innovative, quenched, cathepsin-targeted, fluorescent molecular probe to enhance resection quality for several solid-tumor cancers. Unlike other formulations for imaging probes or tracers in development and entering the clinic, which require systemic administration hours before the procedure, this current formulation is applied topically into the surgical cavity immediately after a standard of care resection. Within minutes of application, the probe activates in the presence of residual cancer in the surgical wound and provides a strong fluorescent signal that precisely delineates any remaining cancer, enabling a more complete resection. Utilization of this imaging gel formulation for topical application to detect breast cancer in the surgical cavity during surgery has the potential to reduce re-excisions, with consequent savings in healthcare costs and enhancement in patient quality of life. Background: Tumor-positive surgical margins during primary breast cancer (BCa) surgery are associated with a two-fold increase in the risk of local recurrence when compared with tumor-negative margins. Pathological microscopic evaluation of the samples only assesses about 1/10 of 1% of the entire volume of the removed BCa specimens, leading to margin under-sampling and potential local recurrence in patients with pathologically clean margins, i.e., false negative margins. In the case of tumor-positive margins, patients need to undergo re-excision and/or radiation therapy, resulting in increases in complications, morbidity, and healthcare costs. Development of a simple real-time imaging technique to identify residual BCa in the surgical cavity rapidly and precisely could significantly improve the quality of care. Methods: A small-molecule, fluorescently quenched protease-substrate probe, AKRO-QC-ICG, was tested as part of a thermosensitive imaging gel formulated for topical application and imaging of the BCa surgical cavity. Results: More than forty formulations of gel mixtures were investigated to enable easy fluid application and subsequent solidification once applied, preventing dripping and pooling in the surgical cavity. The final formulation was tested using human BCa orthotopic implants in nude and NSG patient-derived xenografts (PDX) mice. This formulation of Pluronic F-127/DMSO/AKRO-QC-ICG imaging gel was found to be a good solvent for the probe, with a desirable thermo-reversible solid-gel transition and mechanical strength for distribution of AKRO-QC-ICG on the surfaces of tissue. It demonstrated excellent ability to detect BCa tissue after 10 min exposure, with a high signal-to-noise ratio both in mouse xenografts and freshly excised human lumpectomy tissue. The in vivo efficacy of the AKRO-QC-ICG imaging gel to detect BCa revealed the levels of sensitivity/specificity = 0.92/1 in 12 nude mice, which was corroborated with the sensitivity/specificity = 0.94/1 in 10 PDX mice. Conclusions: Utilization of Pluronic F-127/DMSO/AKRO-QC-ICG imaging gel for topical application to detect BCa in the surgical cavity during surgery has the potential to reduce re-excisions, with consequent savings in healthcare costs and enhancement in patient quality of life. Show less
Lung cancer is the most common cancer type worldwide, with non-small cell lung cancer (NSCLC) being the most common subtype. Non-disseminated NSCLC is mainly treated with surgical resection. The... Show moreLung cancer is the most common cancer type worldwide, with non-small cell lung cancer (NSCLC) being the most common subtype. Non-disseminated NSCLC is mainly treated with surgical resection. The intraoperative detection of lung cancer can be challenging, since small and deeply located pulmonary nodules can be invisible under white light. Due to the increasing use of minimally invasive surgical techniques, tactile information is often reduced. Therefore, several intraoperative imaging techniques have been tested to localize pulmonary nodules, of which near-infrared (NIR) fluorescence is an emerging modality. In this systematic review, the available literature on fluorescence imaging of lung cancers is presented, which shows that NIR fluorescence-guided lung surgery has the potential to identify the tumor during surgery, detect additional lesions and prevent tumor-positive resection margins. Show less
Manen, L. van; Handgraaf, H.J.M.; Diana, M.; Dijkstra, J.; Ishizawa, T.; Vahrmeijer, A.L.; Mieog, J.S.D. 2018
