Intraoperative detection and removal of microscopic residual sarcoma using wide‐field imaging

Abstract

BACKGROUND: The goal of limb-sparing surgery for a soft tissue sarcoma of the extremity is to remove all malignant cells while preserving limb function. After initial surgery, microscopic residual disease in the tumor bed will cause a local recurrence in approximately 33% of patients with sarcoma. To help identify these patients, the authors developed an in vivo imaging system to investigate the suitability of molecular imaging for intraoperative visualization. METHODS: A primary mouse model of soft tissue sarcoma and a wide field-of-view imaging device were used to investigate a series of exogenously administered, near-infrared (NIR) fluorescent probes activated by cathepsin proteases for real-time intraoperative imaging. RESULTS: The authors demonstrated that exogenously administered cathepsin-activated probes can be used for image-guided surgery to identify microscopic residual NIR fluorescence in the tumor beds of mice. The presence of residual NIR fluorescence was correlated with microscopic residual sarcoma and local recurrence. The removal of residual NIR fluorescence improved local control. CONCLUSIONS: The authors concluded that their technique has the potential to be used for intraoperative image-guided surgery to identify microscopic residual disease in patients with cancer. Cancer 2012. © 2012 American Cancer Society.

Smart nanosystems: Bio-inspired technologies that interact with the host environment

“…Translational challenges include manufacturing and regulatory hurdles in addition to the unanticipated complexity of how nanoparticulate materials can interact with the host architecture and biology. The first targeted nanomedicines [CALAA-01 (65); BIND-014 (66)] and smart probes [Lumicell (67)] are now entering human studies, demonstrating feasibility, and will inform design criteria for future generation of nanosystems as the pipeline matures. In an era of precision medicine, in which there is an increasing emphasis on disease stratification for personalized therapeutics, we envision that smart, environmentally responsive therapeutics may offer a complementary approach that instead collapses the treatment of distinct subtypes to a single formulation that is responsive to an individual's disease.…”

Advances in fluorescent-image guided surgery

“…LUM015 was injected intravenously into 15 patients with either invasive ductal carcinoma or soft tissue sarcoma and was well tolerated with no adverse pharmacological activity (36). Tumors were surgically removed and examined ex vivo by fluorescent imaging (36,38). Six hours after injection, fluorescence signal in tumors was significantly higher than in adipose tissue or muscle, demonstrating the tumorselective biodistribution and activation of LUM015 (36).…”

Intraoperative Photodynamic Surgery (iPDS) with Acridine Orange for Musculoskeletal Sarcomas

“…It would result in good functioning of organs or tissues. However, no such ideal method has been devised yet, although there are scattered reports of the use of various kinds of fluorescence dyes towards achieving this purpose [1][2][3][4][5]. The present review paper introduces one such ideal agent that could aid surgeons in realizing their dream: acridine orange (AO).…”

“…It causes minimal damage to normal tissues like major nerves, vessels, muscles, bones and joints, etc. [4]. It may be better to call such treatment photodynamic surgery (PDS).…”