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

Gamma camera piatta a scintillazione, ad altissima risoluzione spaziale, a struttura modulare /Flat scintillation gamma camera with very high spatial resolution,with modular structure

The gamma camera, able to be developed in areas of any size and unlimited, presents such a thickness as to be considered flat and of minimal bulk and it can be assembled in individual modules to be attached one to the other solving the problem of dead zones between individual PSPMTS, with values of intrinsic spatial resolution in the order of 1 mm. The application of the present invention may range from the medical field (PET, SPECT, SPEM, PEM, etc.) to employment in astrophysics

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

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

FMR1 deletion in rats induces hyperactivity with no changes in striatal dopamine transporter availability

: Autism Spectrum Disorder (ASD) is a pervasive neurodevelopmental disorder emerging in early life characterized by impairments in social interaction, poor verbal and non-verbal communication, and repetitive patterns of behaviors. Among the best-known genetic risk factors for ASD, there are mutations causing the loss of the Fragile X Messenger Ribonucleoprotein 1 (FMRP) leading to Fragile X syndrome (FXS), a common form of inherited intellectual disability and the leading monogenic cause of ASD. Being a pivotal regulator of motor activity, motivation, attention, and reward processing, dopaminergic neurotransmission has a key role in several neuropsychiatric disorders, including ASD. Fmr1 Δexon 8 rats have been validated as a genetic model of ASD based on FMR1 deletion, and they are also a rat model of FXS. Here, we performed behavioral, biochemical and in vivo SPECT neuroimaging experiments to investigate whether Fmr1 Δexon 8 rats display ASD-like repetitive behaviors associated with changes in striatal dopamine transporter (DAT) availability assessed through in vivo SPECT neuroimaging. At the behavioral level, Fmr1 Δexon 8 rats displayed hyperactivity in the open field test in the absence of repetitive behaviors in the hole board test. However, these behavioral alterations were not associated with changes in striatal DAT availability as assessed by non-invasive in vivo SPECT and Western blot analyses

FMR1 deletion in rats induces hyperactivity with no changes in striatal dopamine transporter availability

Abstract Autism Spectrum Disorder (ASD) is a pervasive neurodevelopmental disorder emerging in early life characterized by impairments in social interaction, poor verbal and non-verbal communication, and repetitive patterns of behaviors. Among the best-known genetic risk factors for ASD, there are mutations causing the loss of the Fragile X Messenger Ribonucleoprotein 1 (FMRP) leading to Fragile X syndrome (FXS), a common form of inherited intellectual disability and the leading monogenic cause of ASD. Being a pivotal regulator of motor activity, motivation, attention, and reward processing, dopaminergic neurotransmission has a key role in several neuropsychiatric disorders, including ASD. Fmr1 Δ exon 8 rats have been validated as a genetic model of ASD based on FMR1 deletion, and they are also a rat model of FXS. Here, we performed behavioral, biochemical and in vivo SPECT neuroimaging experiments to investigate whether Fmr1 Δ exon 8 rats display ASD-like repetitive behaviors associated with changes in striatal dopamine transporter (DAT) availability assessed through in vivo SPECT neuroimaging. At the behavioral level, Fmr1 Δ exon 8 rats displayed hyperactivity in the open field test in the absence of repetitive behaviors in the hole board test. However, these behavioral alterations were not associated with changes in striatal DAT availability as assessed by non-invasive in vivo SPECT and Western blot analyses

Radioisotope guided surgery with imaging probe, a hand-held high-resolution gamma camera

Since 1997, our group of Physics together with Nuclear Physicians studies imaging probes (IP), hand-held, high-resolution gamma cameras for radio-guided surgery (RGS). Present work is aimed to verify the usefulness of two updated IP in different surgical operations. Forty patients scheduled for breast cancer sentinel node (SN) biopsy, five patients with nodal recurrence of thyroid cancer, seven patients with parathyroid adenomas, five patients with neuroendocrine tumours (NET), were operated under the guide of IP. We 2 used two different IP with field of view of 1 and 4in.(2), respectively and intrinsic spatial resolution of about 2mm. Radioisotopes were (99m)Tc, (123)I and (111)In. The 1 in.(2) IP detected SN in all the 40 patients and more than one node in 24, whereas anger camera (AC) failed locating SN in four patients and detected true positive second nodes in only nine patients. The 4 in.(2) IP was used for RGS of thyroid, parathyroid and NETs. It detected eight latero-cervical nodes. In the same patients, AC detected five invaded nodes. Parathyroid adenomas detected by IP were 10 in 7 patients, NET five in five patients. One and 4 in.(2) IPs showed usefulness in all operations. Initial studies on SN biopsy were carried out on small series of patients to validate IP and to demonstrate the effectiveness and usefulness of IP alone or against conventional probes. We propose the use of the IP as control method for legal documentation and surgeon strategy guide before and after lesion(s) removal. (c) 2007 Elsevier B.V. All rights reserved

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