R. Massari

High-Resolution, Hand-Held Camera for Sentinel-Node Detection

BACKGROUND The imaging probe (IP) is a high-resolution (HR), 1-in(2) field-of-view hand-held gamma camera. We used it to detect breast cancer sentinel node (SN). PATIENTS AND METHODS We divided 120 T1 breast cancer patients, who underwent Anger camera lymphoscintigraphy (ACL), in two subgroups of 60 patients who were age, body mass index, and cancer size matched: subgroup A (SA) and B (SB). SN was detected with a common gamma probe (GP) in SA, with IP plus GP in SB. RESULTS Surgeons removed radioactive nodes without exceeding four nodes. Eighty-two (82) SNs were taken off in SA and 105 in SB (p<0.01). Of SA, 22 of 60 patients and 36 of 60 patients of SB showed more than 1 node, and 3 of them showed 3 nodes and 1 showed 4 nodes. Thirteen (13) patients resulted N(+) (21.6%) in SA. Ten (10) patients of SA showed an invasion on the hottest nodes and 3 on the second nodes. In the SB, 18 patients (25%) showed invasion. Sixteen (16) invasions were on hot, 4 on second, and 1 on the third node. Withdrawal time of SN was 11.25+/-4.7 minutes for SA and 7.4+/-2.8 minutes for SB (p<0.025). CONCLUSIONS SN biopsy with IP is fast and discovers more SNs and more invasions than ACL.

Thyroid cancer imaging in vivo by targeting the anti-apoptotic molecule galectin-3.

Background The prevalence of thyroid nodules increases with age, average 4–7% for the U.S.A. adult population, but it is much higher (19–67%) when sub-clinical nodules are considered. About 90% of these lesions are benign and a reliable approach to their preoperative characterization is necessary. Unfortunately conventional thyroid scintigraphy does not allow the distinction among benign and malignant thyroid proliferations but it provides only functional information (cold or hot nodules). The expression of the anti-apoptotic molecule galectin-3 is restricted to cancer cells and this feature has potential diagnostic and therapeutic implications. We show here the possibility to obtain thyroid cancer imaging in vivo by targeting galectin-3. Methods The galectin-3 based thyroid immuno-scintigraphy uses as radiotracer a specific 99mTc-radiolabeled mAb. A position-sensitive high-resolution mini-gamma camera was used as imaging capture device. Human galectin-3 positive thyroid cancer xenografts (ARO) and galectin-3 knockout tumors were used as targets in different experiments in vivo. 38 mice with tumor mass of about 1 gm were injected in the tail vein with 100 µCi of 99mTc-labeled mAb to galectin-3 (30 µg protein/in 100 µl saline solution). Tumor images were acquired at 1 hr, 3 hrs, 6 hrs, 9 hrs and 24 hrs post injection by using the mini-gamma camera. Findings Results from different consecutive experiments show an optimal visualization of thyroid cancer xenografts between 6 and 9 hours from injection of the radiotracer. Galectin-3 negative tumors were not detected at all. At 6 hrs post-injection galectin-3 expressing tumors were correctly visualized, while the whole-body activity had essentially cleared. Conclusions These results demonstrate the possibility to distinguish preoperatively benign from malignant thyroid nodules by using a specific galectin-3 radio-immunotargeting. In vivo imaging of thyroid cancer may allow a better selection of patients referred to surgery. The possibility to apply this method for imaging and treatment of other galectin-3 expressing tumors is also discussed.

Radiolabeled Humanized Anti-CD3 Monoclonal Antibody Visilizumab for Imaging Human T-Lymphocytes

Visilizumab is an IgG2 humanized monoclonal antibody (mAb) characterized by non-FcγR binding and specific to the CD3 antigen, expressed on more than 95% of circulating resting T-lymphocytes and on activated T-lymphocytes homing in inflamed tissues. We hypothesized that the use of a radiolabeled anti-CD3 antibody might serve as a diagnostic tool for imaging T-cell traffic and lymphocytic infiltration of tissues and organs affected by autoimmune diseases. Here we describe the results of in vitro and animal experiments with 99mTc-succinimidyl-6-hydrazinonicotinate hydrochloride (SHNH)–visilizumab. Methods: For mAb labeling, we used a 2-step method with a heterobifunctional linker SHNH. Several titrations were performed to obtain the best labeling efficiency. In vitro quality controls included stability assay, cysteine challenge, sodium dodecyl sulfate polyacrylamide gel electrophoresis, binding assay, and immunoreactivity assay. In vivo studies by high-resolution images were performed at 6 and 24 h after the injection of 99mTc-SHNH–visilizumab. These included cell-targeting experiments in BALB/c mice xenografted subcutaneously with an increasing number of HuT78 cells in the leg and displaced with an excess of cold antibody. We also studied irradiated severe combined immunodeficient (SCID) mice reconstituted with human peripheral blood mononuclear cells (hPBMCs) and injected with 99mTc-labeled visilizumab or control mAb. After dynamic imaging for 3 h, major organs were removed, counted, and processed for immunohistologic examination. Results: Visilizumab was labeled with HYNIC with high labeling efficiency (>90%) and high specific activity (SA; 10,360–11,100 MBq/mg), with retained biochemical integrity and in vitro binding activity to CD3-positive cells. The in vivo targeting experiment showed a proportional increase of specific uptake with the number of injected cells, both at 6 and at 24 h, and the in vivo competition study demonstrated more than 60% decreased uptake after an excess of unlabeled antibody. In SCID mice, hPBMCs in different tissues were detected by 99mTc-labeled visilizumab and confirmed by histology. Conclusion: Visilizumab can be efficiently labeled with 99mTc with high efficiency and SA and could be a valuable tool for the study of human T-lymphocyte trafficking and lymphocytic infiltration of tissues and organs.

Low power readout circuits for large area silicon photomultiplier array

In this paper we present modeling and experimental characterization of two passive charge division circuits as low power readout systems for large area silicon photomultiplier (SiPM) array. The first configuration is the traditional discrete positioning circuit (DPC), while the second one is a symmetric charge division circuit where the SiPM output current is split into two symmetric signals by a pair of diodes. Testing the two CDC networks on a 16 × 28 array of SiPMs, we found that image reconstruction is significantly compromised when the DPC configuration is connected to few SiPMs, while the diode-based CDC configuration presents a very high quality image histogram independently on the number of the connected photosensors. These results demonstrate the efficacy of the proposed diode-based CDC as passive readout circuitry and open the route for the development of effective low-power consumption, portable gamma camera systems.

Low-Power Charge Division Circuits for Wireless Applications Based on Silicon Photomultipliers

In this paper, we present a dedicated charge division circuit (CDC) as readout system for wireless detectors based on silicon photomultiplier (SiPM) arrays coupled to scintillators. In the proposed readout circuit, the SiPM output current is split into two symmetric signals by a pair of diodes, so it was called diode coupled symmetric charge division (DCSCD). The circuit was investigated using LTSPICE, fabricated as a printed circuit board and characterized. Its performances were compared with that of the traditional discrete positioning circuit (DPC) scheme. Testing the two CDC networks on a 16 × 28 array of SiPMs, we found that image reconstruction is significantly compromised when the DPC configuration is connected to few SiPMs, while the diode-based CDC configuration presents a very high-quality image histogram independently on the number of the connected photosensors. The proposed electronics features very low-power consumption when compared with commercial solutions and it is, therefore, suitable for battery-operated device, which requires a power-efficient design. Indeed, the DCSCD electronics requires less than 10 mW of static power to read out the 16 × 28 array of SiPMs, demonstrating the efficacy of the proposed diode-based CDC as passive readout circuitry and opening the route for the development of wireless gamma camera systems.

Directional probe for radio‐guided surgery: A pilot study

PURPOSE The sentinel lymph node (SLN) biopsy technique has highly evolved during the last 20 yr. Consequently, the intraoperative use of Gamma Probes (GPs) for SLN mapping is increased. This preliminary study evaluates a novel directional GP prototype. This proof-of-concept prototype is designed to identify the direction of radiopharmaceuticals uptakes, by combining the information from multiple detectors. The purpose of this work is to develop a tool able to effectively guide the surgeon reducing the surgery time. METHODS The proposed prototype consists of three CsI(Tl) scintillation crystals, each coupled with an S10931 silicon photomultiplier (Hamamatsu Photonics K.K., Hamamatsu, JP). The three detectors lie on the same plane with an angle of 30° between them. The central detector is placed as in a common GP, so it can be used to pinpoint the target tissue. Meanwhile, the lateral sensors provide a broader view of the surgical field. A dedicated data acquisition system digitizes and processes the signals from the front-end electronics. Finally, an embedded system, based on ARM processor, calculates and displays the acquired count rates. In order to assess the prototype behavior, the isosensitivity curves for the three detectors were measured. Meanwhile, for the central one, the main quality criteria measurements were also performed (i.e., sensitivity, radial sensitivity, and spatial resolution). RESULTS For the central detector, the measured sensitivity at the tip of the probe is better than 5 cps/kBq. The full width at half maximum (FWHM) of the radial sensitivity is less than 30° and the FWHM of the lateral sensitivity (spatial resolution) is about 7.2 mm. The central detector measured isosensitivity distribution shows a narrow profile in agreement with the spatial resolution measured. On the contrary, the two lateral detectors exhibit widespread isosensitivity distributions that mean a larger field of view. The system had shown satisfactory performance and reliability, meeting the minimal requirements of gamma probe systems. CONCLUSIONS The prototype presented in this paper allows a rapid localization by the use of the whole system, while the sole central detector can be used to pinpoint the target source. This device, unlike common GPs, allows localizing simultaneously different areas of radiopharmaceuticals uptake, thus precisely guiding the surgeon to the region of interest. These preliminary results encourage to develop a further prototype for intraoperative validation.