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 ?Ci of 99mTc-labeled mAb to galectin-3 (30 ?g protein/in 100 ?l 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

High resolution mini-gammacamera and 99mTc [HMPAO] - leukocytes for diagnosis of infection and radioguided surgery in diabetic foot

Discovery of osteitis may be delayed because of late appearance of X-ray signs in patients with diabetic foot. Scintigraphy with labelled leukocytes is able to detect flogosis but often misses bone involvement, due to inadequate resolution of Anger camera, the commonest detector used in nuclear medicine. Radioguided surgery and biopsy with high resolution scintigraphy (HRS) started to be studied since 2000: although this method had never been tested for planning and guiding diabetic foot surgery, in our opinion it can help early diagnosis and surgical treatment of diabetic foot. Five patients with diabetic foot and suspected infection were studied with standard 99mTc [HMPAO]-leukocyte scan. In the same patients 2 mm spatial resolution HRS was performed 24 hours after administration of labelled WBC, using our inch2 field-of-view portable mini-gammacamera. Operations were done just after the 24h scan and were guided with the portable high resolution device in the four patients who showed positive scan. Scintigraphy with Anger camera and HRS were positive in four patients. HRS showed a bar-shaped radioactivity corresponding to small phalanges, close to the main inter-digital hot spot. The presence of osteitis on phalanges that had been shown by HRS was confirmed at surgery, that was successfully driven with the high resolution mini-camera. In conclusion HRS is able to diagnose early osteitis of diabetic foot and to guide diabetic foot surgery

Anti-cytokine autoantibodies in autoimmune diseases

An overview of the current literature is showing that autoantibodies (AutoAbs) against cytokines are produced in several pathological conditions, including autoimmune diseases, but can also be detected in healthy individuals. In autoimmune diseases, these AutoAbs may also be prognostic markers, either negative (such as AutoAbs to IL-8 and IL-1\u3b1 in rheumatoid arthritis) or positive (such as AutoAbs to IL-6 in systemic sclerosis and those to osteopontin in rheumatoid arthritis). They may have neutralizing activity and influence the course of the physiological and pathological immune responses. High levels of AutoAbs against cytokines may even lead to immunodeficiency, such as those to IL-17 in autoimmune polyendocrine syndrome type I or those to IFN-\u3b3 in mycobacterial infections. Their role in human therapy may be exploited not only through passive immunization but also through vaccination, which may improve the costs for long lasting treatments of autoimmune diseases. Detection and quantification of these AutoAbs can be profoundly influenced by the technique used and standardization of these methods is needed to increase the value of their analysis

Evaluation of a combined array-planar crystal for gamma-ray scintillation imagers

Over the last few years our interest was dedicated to the development of small field of view imagers for Nuclear Medicine applications, particularly in Oncology. Some years ago, the authors have described an original scintillation gamma camera based on a matrix of 2 x 2 R5900-C8 Hamamatsu Position Sensitive PhotoMultiplier Tube (PSPMT) coupled to a scintillating array. The intrinsic spatial resolution obtained was adequate for high-resolution imaging applications. On the contrary, the prototype was affected by reduced performances at the borders between PSPMT. The subsequent introduction by Hamamatsu of the R7600 flange-less PSPMT family allowed to reduce the dead areas at the borders. Furthermore, Hamamatsu R7600-C12 model, improving the charge sampling with lower anode pitch, allows to improve the spatial resolution and to optimize the spatial response. Good performance was obtained with 2 x 2 R5900-C8 PSPMT array with a Combined Array-Planar Crystal (CAPC) geometry, designed by the authors. It consists of a planar crystal segmented in the top in a 15 x 15 array, 3 mm square pixel, 1 mm thick, and 0.25 mm gap. Hilger manufactured two CsI assemblies, Na and T1 doped, respectively, for this study. (C) 2002 Elsevier Science B.V. All rights reserved

Imaging probe for breast cancer localization

High spatial resolution, small Field Of View (FOV), fully portable scintillation cameras are lower cost and obviously lower weight than large FOV, not transportable Anger gamma cameras. Portable cameras allow easy transfer of the detector, thus of radioisotope imaging, where the bioptical procedure takes place. In this paper we describe a preliminary experience on radionuclide Breast Cancer (BC) imaging with a 22.8 x 22.8 mm(2) FOV minicamera, already used by our group for sentinel node detection with the name of Imaging Probe (IP). In this work IP BC detection was performed with the aim of guiding biopsy, in particular open biopsy, or to help or modify fine needle or needle addressing when main driving method was echography or digital radiography. The IP prototype weight was about I kg. This small scintillation camera is based on the compact Position Sensitive Photomultiplier Tube Hamamatsu R7600-00-C8, coupled to a CsI(TI) scintillation array 2.6 x 2.6 x 5.0 mm(3) crystal-pixel size. Spatial resolution of the IP was 2.5 mm Full-Width at Half-Maximum at laboratory tests. IP was provided with acquisition software allowing quick change of pixels number on the computer acquisition frame and an on-line image-smoothing program. Both these programs were developed in order to allow nuclear physicians to quickly get target source when the patient was anesthetized in the operator room, with sterile conditions. Tc-99m Sestamibi (MIBI) was injected at the dose of 740 MBq 1 h before imaging and biopsy to 14 patients with suspicious or known BC. Scintigraphic images were acquired before and after biopsy in each patient. Operator was allowed to take into account scintigraphic images as well as previously performed X-ray mammograms and echographies. High-resolution IP images were able to guide biopsy toward cancer or washout zones of the cancer, that are thought to be chemoresistant in 7 patients out of 10. Four patients, in whom IP and MIBI were not able to guide biopsy, did not show cancer. Two patients in whom biopsy was performed in the high washout zone, did show Multi Drug Resistance (MDR) gene product at immunohistochemistry on bioptical samples. Specific radioactivity was measured on biopsy specimens and measurement confirmed the etherogeneous distribution of MIBI within cancers. Our study confirms the ability of IP to guide breast biopsy even when our mini-camera has to be manually handled by trained physicians during operation. (C) 2002 Elsevier Science B.V. All rights reserved

Factors affecting cancer detectability in 99Tc MIBI scintimammography

Scintimammography shows strong potential in detecting and differentiating breast cancer. This scintigraphic technique, using a standard gamma camera, allows high sensitivity and specificity values (>95%) for detected tumors more than 1cm size. However, the sensitivity of scintimammography using conventional gamma cameras is considerably less (40-50%) for tumors with smaller size. Recently, the authors demonstrated how the use of a small FOV dedicated gamma camera (Single Photon Emission Mammography, or SPEM camera), with very high intrinsic spatial resolution (1.7mm FWHM), working with breast moderately compressed and positioned close to the breast tumor (i.e., analogously to X-ray mammography) increased sensitivity up to 80% for tumors sized between 0.5 and 1cm (T1b). The aim of this paper is to demonstrate how the reduced breast thickness can play a primary role in small cancer detection. Five different methods were taken into account: clinical measurements, comparing tumor SNR values obtained from the same patients in prone scintimammography and in SPEM, comparing SNR values between compressed and uncompressed breast in craniocaudal projection, breast phantom measurements, Monte Carlo simulations and simplified theoretical model. Results confirm that the mechanism for the improvement in visualizing sub-centimeter lesions due to compression is a reduction of lesion-detector distance. As a result of this reduced distance there is a less reabsorption of signal by interposed breast tissue, and improved detector intrinsic spatial resolution. © 2002 Elsevier Science B.V. All rights reserved

The role of breast compression in scintimammography

Phantom model was performed to study the effect of breast compression on signal-to-noise ratio (SNR) for a dedicated high-resolution gamma camera (Single Photon Emission Mammography, or 'SPEM') and a conventional one as typically employed in prone scintimammography. The phantom was designed to simulate the effects of lesion size and of scatter from nearby torso activity. The phantom studies showed that lesions SNR was higher with the SPEM camera than with the conventional camera, and that SNR was always improved with compression for both cameras. Since the stage of breast cancer diagnosis affects patient prognosis, it is important to optimize breast examinations for small (i.e., T1a and T1b) lesions. For one-cm size lesions (clinical stage T1c), SNR was maximized when compression was less than 12 cm, and little additional benefit was derived from further compression. For subcentimeter (clinical stage T1b) lesions, SNR was maximized when compression was less than 6 cm. These data are consistent with a short clinical study in which detection sensitivity for small cancers was improved with the SPEM camera as compared to a conventional gamma camera. We conclude that, in order to image early breast cancers (stage T1b), it is important to apply breast compression

A detector for submillimeter gamma cameras

Anger cameras (SPECT etc.) presently used in nuclear medicine employ as active detector NaI crystals, obtaining intrinsic spatial resolutions greater than or equal to 3mm. Arrays made of optically isolated single crystal elements of YAP:Ce, having sub-millimeter aperture size, read out by position sensitive photomultipliers, allow to build active detectors to employ in SPECT systems, with intrinsic spatial resolution below the millimeter, and with time resolution of the order of tens of nanoseconds. In this paper preliminary results of measurements carried on different kinds of YAP:Ce arrays are reported. The measurements have been performed aiming to optimize the geometrical and physical parameters of the crystals in order to accomplish a SPEM (Single Photon Emission Mammography) camera detector