Prototype device for endoventricular beta-emitting radiotracer detection and molecularly-guided intervention.

BACKGROUND: We have set out to develop a catheter-based theranostic system that: (a) identifies diseased and at-risk myocardium via endocardial detection of systemically delivered ß-emitting radiotracers and (b) utilizes molecular signals to guide delivery of therapeutics to appropriate tissue via direct intramyocardial injection. METHODS: Our prototype device consists of a miniature ß-radiation detector contained within the tip of a flexible intravascular catheter. The catheter can be adapted to incorporate an injection port and retractable needle for therapeutic delivery. The performance of the ß-detection catheter was assessed in vitro with various ß-emitting radionuclides and ex vivo in hearts of pigs following systemic injection of 18F-fluorodeoxyglucose (18F-FDG) at 1-week post-myocardial infarction. Regional catheter-based endocardial measurements of 18F activity were compared to regional tissue activity from PET/CT images and gamma counting. RESULTS: The ß-detection catheter demonstrated sensitive in vitro detection of ß-radiation from 22Na (ß+), 18F (ß+), and 204Tl (ß-), with minimal sensitivity to γ-radiation. For 18F, the catheter demonstrated a sensitivity of 4067 counts/s/µCi in contact and a spatial resolution of 1.1 mm FWHM. Ex vivo measurements of endocardial 18F activity with the ß-detection catheter in the chronic pig infarct model demonstrated good qualitative and quantitative correlation with regional tissue activity from PET/CT images and gamma counting. CONCLUSION: The prototype ß-detection catheter demonstrates sensitive and selective detection of ß- and ß+ emissions over a wide range of energies and enables high-fidelity ex vivo characterization of endocardial activity from systemically delivered 18F-FDG.

PET-Probe: Evaluation of Technical Performance and Clinical Utility of a Handheld High-Energy Gamma Probe in Oncologic Surgery.

BACKGROUND: Positron emission tomography (PET) has become an invaluable part of patient evaluation in surgical oncology. PET is less than optimal for detecting lesions <1 cm, and the intraoperative localization of small PET-positive lesions can be challenging as a result of difficulties in surgical exposure. We undertook this investigation to assess the utility of a handheld high-energy gamma probe (PET-Probe) for intraoperative identification of 18F-deoxyglucose (FDG)-avid tumors. METHODS: Forty patients underwent a diagnostic whole-body FDG-PET scan for consideration for surgical exploration and resection. Before surgery, all patients received an intravenous injection of 7 to 10 mCi of FDG. At surgery, the PET-Probe was used to determine absolute counts per second at the known tumor site(s) demonstrated by whole-body PET and at adjacent normal tissue (at least 4 cm away from tumor-bearing sites). Tumor-to-background ratios were calculated. RESULTS: Thirty-two patients (80%) underwent PET-Probe-guided surgery with therapeutic intent in a recurrent or metastatic disease setting. Eight patients underwent surgery for diagnostic exploration. Anatomical locations of the PET-identified lesions were neck and supraclavicular (n = 8), axilla (n = 5), groin and deep iliac (n = 4), trunk and extremity soft tissue (n = 3), abdominal and retroperitoneal (n = 19), and lung (n = 2). PET-Probe detected all PET-positive lesions. The PET-Probe was instrumental in localization of lesions in 15 patients that were not immediately apparent by surgical exploration. CONCLUSIONS: The PET-Probe identified all lesions demonstrated by PET scanning and, in selected cases, was useful in localizing FDG-avid disease not seen with conventional PET scanning.

An analysis of the utility of handheld PET probes for the intraoperative localization of malignant tissue.

INTRODUCTION: The intraoperative localization of suspicious lesions detected by positron emission tomography (PET) scan remains a challenge. To solve this, two novel probes have been created to accurately detect the (18)F-FDG radiotracer intraoperatively. METHODS: Nude rats were inoculated with mesothelioma. When PET scans detected 10-mm tumors, animals were dissected and the PET probes analyzed the intraoperative radiotracer uptake of these lesions as tumor to background ratio (TBR). RESULTS: The 17 suspicious lesions seen on PET scan were localized intraoperatively (by their high TBR) using the PET probes and found malignant on pathology. Interestingly, smaller tumors not visualized on PET scan were detected intraoperatively by their high TBR and found malignant on pathology. Furthermore, using a TBR threshold as low as 2.0, both gamma (sensitivity, 100%; specificity, 80%; positive predictive value (PPV), 96%; and negative predictive value (NPV), 100%) and beta (sensitivity, 100%; specificity, 60%; PPV, 93%; and NPV, 100%) probes reliably detected suspicious lesions on PET scan imaging. They also showed an excellent area under the curve of 0.9 and 0.97 (95% CI of 0.81-0.99 and 0.93-1.0) for gamma and beta probes, respectively, in the receiver operating characteristic analysis for detecting malignancy. CONCLUSION: This novel tool could be used synergistically with a PET scan imaging to maximize tissue selection intraoperatively.

Portable PET probes are a novel tool for intraoperative localization of tumor deposits.

BACKGROUND: Positron emission tomography (PET) identifies cancer deposits by detecting sites of gamma emissions that are released from radioactively labeled molecules targeting tumor to formulate a PET image. Correlating preoperative PET scans with intraoperative findings remains a challenge. We investigated whether high-energy gamma emissions detected by a novel hand-held PET probe would detect tumors and offer a real-time method to localize tumor intraoperatively. Furthermore, we investigated the novel beta probe, which detects emissions at a shorter range than gamma emissions, making them undetectable by PET scanners, but potentially valuable for close range intraoperative detection of tumor deposits. METHODS: Six-to-eight-week-old athymic mice were injected with one of four possible tumor cell lines: gastric, pancreas, squamous cell and breast cancer. After tumors reached at least 1 cm in size, they were euthanized and imaged with a micro-PET imager. Hand-held gamma and beta probes were then used in vivo and ex vivo to measure high-energy gamma and beta emissions. RESULTS: The portable PET probes detected high-energy gamma and beta emissions from all tumors evaluated. These emissions were reproducible and we established that beta emissions correlate with high-energy gamma emissions and conventional PET scans. There was a strong positive correlation (R = 0.8) between gamma and beta counts. Beta emission showed a stronger correlation than gamma emission with overall tissue radioactivity. CONCLUSION: This study is the first to demonstrate that gamma emission detected by conventional PET imaging correlates with beta emissions. This study shows that compared to detection of gamma emissions, beta counts may offer superior real-time localization of tumor deposits. Intraoperative portable PET probe may become a useful way to exploit tumor biology and PET technology to guide real-time tissue characterization during surgery.

A novel method to localize antibody-targeted cancer deposits intraoperatively using handheld PET beta and gamma probes.

BACKGROUND: Assessing cancer margins, lymph nodes, and small cancer deposits intraoperatively can be challenging. A new device has become available that allows the detection of positron emission tomography (PET) radiotracers through both high-energy gamma and short-range beta emissions. These PET probes are handheld, allowing for real-time evaluation of cancer using a tool that provides surgeons with better intraoperative assessment of tumor sites. METHODS: Within the context of two institutional review board (IRB)-approved protocols investigating new applications of antibody-labeled PET scanning, (124)I-labeled humanized monoclonal antibodies specific for colorectal cancer (huA33) and renal tumors (cG250) were constructed. Patients underwent preoperative PET scans, approximately seven days post-tracer infusion, when tumor-to-nontumor ratios were high. Suspected tumor deposits were evaluated intraoperatively with handheld beta and gamma PET probes. RESULTS: Handheld PET probes detected emissions from all tumors. Count rates from the gamma probe on tumor ranged from 48 to 306 cps, and for the beta probe ranged from 18 to 190 cps. Gamma and beta emissions exhibited a strong positive correlation. The ratio of gamma and beta counts was at least twice that of the background counts for all tumors evaluated. CONCLUSIONS: This study is the first to demonstrate the utility of beta probes for the intraoperative detection of radiolabeled antibodies targeting cancer. Importantly, the recorded beta count rates from the beta probe correlate with the count rates from the high-energy gamma probe. Furthermore, the beta probe may offer superior specificity for real-time localization of small tumor deposits, compared to gamma probes. The intraoperative portable PET probe may prove a valuable bridge to combining tumor biology and PET technology to guide surgical therapy.

Real-time fusion of ultrasound and gamma probe for navigated localization of liver metastases.

Liver metastases are an advanced stage of several types of cancer, usually treated with surgery. Intra-operative localization of these lesions is currently facilitated by intra-operative ultrasound (IOUS) and palpation, yielding a high rate of false positives due to benign abnormal regions. In this paper we present the integration of functional nuclear information from a gamma probe with IOUS, to provide a synchronized, real-time visualization that facilitates the detection of active metastases intra-operatively. We evaluate the system in an ex-vivo setup employing a group of physicians and medical technicians and show that the addition of functional imaging improves the accuracy of localizing and identifying malignant and benign lesions significantly. Furthermore we are able to demonstrate that the inclusion of an advanced, augmented visualization provides more reliability and confidence on classifying these lesions in the presented evaluation setup.

Towards intra-operative 3D nuclear imaging: reconstruction of 3D radioactive distributions using tracked gamma probes.

Nuclear medicine imaging modalities assist commonly in surgical guidance given their functional nature. However, when used in the operating room they present limitations. Pre-operative tomographic 3D imaging can only serve as a vague guidance intra-operatively, due to movement, deformation and changes in anatomy since the time of imaging, while standard intra-operative nuclear measurements are limited to 1D or (in some cases) 2D images with no depth information. To resolve this problem we propose the synchronized acquisition of position, orientation and readings of gamma probes intra-operatively to reconstruct a 3D activity volume. In contrast to conventional emission tomography, here, in a first proof-of-concept, the reconstruction succeeds without requiring symmetry in the positions and angles of acquisition, which allows greater flexibility. We present our results in phantom experiments for sentinel node lymph node localization. The results indicate that 3D intra-operative nuclear images can be generated in such a setup up to an accuracy equivalent to conventional SPECT systems. This technology has the potential to advance standard procedures towards intra-operative 3D nuclear imaging and offers a novel approach for robust and precise localization of functional information to facilitate less invasive, image-guided surgery.

Advances in FDG PET probes in surgical oncology.

Whole-body positron emission tomography (WB-PET) has been developed as a sensitive, cost-effective method for imaging malignant disease. WB-PET provides complete body imaging with a single scanning approach for a variety of malignancies. With increasing clinical experience, the indications for its use have broadened. This article reviews current uses of the technology and discusses some potential applications, particularly the utility of a commercially available surgical gamma probe for detecting the gamma particles emitted in the decay process of FDG.