Comparison of two threshold detection criteria methodologies for determination of probe positivity for intraoperative in situ identification of presumed abnormal 18F-FDG-avid tissue sites during radioguided oncologic surgery.

BACKGROUND: Intraoperative in situ identification of (18)F-FDG-avid tissue sites during radioguided oncologic surgery remains a significant challenge for surgeons. The purpose of our study was to evaluate the 1.5-to-1 ratiometric threshold criteria method versus the three-sigma statistical threshold criteria method for determination of gamma detection probe positivity for intraoperative in situ identification of presumed abnormal (18)F-FDG-avid tissue sites in a manner that was independent of the specific type of gamma detection probe used. METHODS: From among 52 patients undergoing appropriate in situ evaluation of presumed abnormal (18)F-FDG-avid tissue sites during (18)F-FDG-directed surgery using 6 available gamma detection probe systems, a total of 401 intraoperative gamma detection probe measurement sets of in situ counts per second measurements were cumulatively taken. RESULTS: For the 401 intraoperative gamma detection probe measurement sets, probe positivity was successfully met by the 1.5-to-1 ratiometric threshold criteria method in 150/401 instances (37.4%) and by the three-sigma statistical threshold criteria method in 259/401 instances (64.6%) (P < 0.001). Likewise, the three-sigma statistical threshold criteria method detected true positive results at target-to-background ratios much lower than the 1.5-to-1 target-to-background ratio of the 1.5-to-1 ratiometric threshold criteria method. CONCLUSIONS: The three-sigma statistical threshold criteria method was significantly better than the 1.5-to-1 ratiometric threshold criteria method for determination of gamma detection probe positivity for intraoperative in situ detection of presumed abnormal (18)F-FDG-avid tissue sites during radioguided oncologic surgery. This finding may be extremely important for reshaping the ongoing and future research and development of gamma detection probe systems that are necessary for optimizing the in situ detection of radioisotopes of higher-energy gamma photon emissions used during radioguided oncologic surgery.

A Concept for Preoperative and Intraoperative Molecular Imaging and Detection for Assessing Extent of Disease of Solid Tumors.

The authors propose a concept of "systems engineering," the approach to assessing the extent of diseased tissue (EODT) in solid tumors. We modeled the proof of this concept based on our clinical experience with colorectal carcinoma (CRC) and gastrinoma that included short and long-term survival data of CRC patients. This concept, applicable to various solid tumors, combines resources from surgery, nuclear medicine, radiology, pathology, and oncology needed for preoperative and intraoperative assessments of a patient's EODT. The concept begins with a patient presenting with biopsy-proven cancer. An appropriate preferential locator (PL) is a molecule that preferentially binds to a cancer-related molecular target (i.e., tumor marker) lacking in non-malignant tissue and is the essential element. Detecting the PL after an intravenous injection requires the PL labeling with an appropriate tracer radionuclide, a fluoroprobe, or both. Preoperative imaging of the tracer's signal requires molecular imaging modalities alone or in combination with computerized tomography (CT). These include positron emission tomography (PET), PET/CT, single-photon emission computed tomography (SPECT), SPECT/CT for preoperative imaging, gamma cameras for intraoperative imaging, and gamma-detecting probes for precise localization. Similarly, fluorescent-labeled PLs require appropriate cameras and probes. This approach provides the surgeon with real-time information needed for R0 resection.

Intraoperative detection of ¹8F-FDG-avid tissue sites using the increased probe counting efficiency of the K-alpha probe design and variance-based statistical analysis with the three-sigma criteria.

BACKGROUND: Intraoperative detection of (18)F-FDG-avid tissue sites during 18F-FDG-directed surgery can be very challenging when utilizing gamma detection probes that rely on a fixed target-to-background (T/B) ratio (ratiometric threshold) for determination of probe positivity. The purpose of our study was to evaluate the counting efficiency and the success rate of in situ intraoperative detection of (18)F-FDG-avid tissue sites (using the three-sigma statistical threshold criteria method and the ratiometric threshold criteria method) for three different gamma detection probe systems. METHODS: Of 58 patients undergoing (18)F-FDG-directed surgery for known or suspected malignancy using gamma detection probes, we identified nine (18)F-FDG-avid tissue sites (from amongst seven patients) that were seen on same-day preoperative diagnostic PET/CT imaging, and for which each (18)F-FDG-avid tissue site underwent attempted in situ intraoperative detection concurrently using three gamma detection probe systems (K-alpha probe, and two commercially-available PET-probe systems), and then were subsequently surgical excised. RESULTS: The mean relative probe counting efficiency ratio was 6.9 (± 4.4, range 2.2-15.4) for the K-alpha probe, as compared to 1.5 (± 0.3, range 1.0-2.1) and 1.0 (± 0, range 1.0-1.0), respectively, for two commercially-available PET-probe systems (P < 0.001). Successful in situ intraoperative detection of 18F-FDG-avid tissue sites was more frequently accomplished with each of the three gamma detection probes tested by using the three-sigma statistical threshold criteria method than by using the ratiometric threshold criteria method, specifically with the three-sigma statistical threshold criteria method being significantly better than the ratiometric threshold criteria method for determining probe positivity for the K-alpha probe (P = 0.05). CONCLUSIONS: Our results suggest that the improved probe counting efficiency of the K-alpha probe design used in conjunction with the three-sigma statistical threshold criteria method can allow for improved detection of 18F-FDG-avid tissue sites when a low in situ T/B ratio is encountered.