F. Scopinaro

Multi-PSPMT scintillating camera

Gamma ray imaging is usually accomplished by the use of a relatively large scintillating crystal coupled to either a number of photomultipliers (PMTs) (Anger Camera) or to a single large Position Sensitive PMT (PSPMT). Recently the development of new diagnostic techniques, such as scintimammography and radio-guided surgery, have highlighted a number of significant limitations of the Anger camera in such imaging procedures. In this paper a dedicated gamma camera is proposed for clinical applications with the aim of improving image quality by utilizing detectors with an appropriate size and shape for the part of the body under examination. This novel scintillation camera is based upon an array of PSPMTs (Hamamatsu R5900-C8). The basic concept of this camera is identical to the Anger Camera with the exception of the substitution of PSPMTs for the PMTs. In this configuration it is possible to use the high resolution of the PSPMTs and still correctly position events lying between PSPMTs. In this work the test configuration is a 2 by 2 array of PSPMTs. Some advantages of this camera are: spatial resolution less than 2 mm FWHM, good linearity, thickness less than 3 cm, light weight, lower cost than equivalent area PSPMT, large detection area when coupled to scintillating arrays, small dead boundary zone (<3 mm) and flexibility in the shape of the camera.

99mTc-bombesin detects prostate cancer and invasion of pelvic lymph nodes

Biopsy is the standard method for the diagnosis of prostate cancer; however, it is inadequate for the assessment of lymph node invasion. Radionuclide imaging might be useful for both diagnosis and N staging, but it requires high uptake of radiotracers in order to overcome difficulties arising from the anatomy of the region. The aim of this study was to assess whether or not technetium-99m labelled bombesin (99mTc-BN) scan is able to detect prostate cancer and invasion of pelvic lymph nodes. Ten patients were studied with 99mTc-BN, transrectal ultrasonography, biopsy, computed tomography and magnetic resonance imaging. All the patients with cancer were operated on. Planar dynamic scintigraphy and single-photon emission tomography (SPET) were performed after administration of 185xa0MBq 99mTc-BN. Two patients showed benign adenoma and eight showed cancer at biopsy. The average Gleasons score was 7.5±1.3. 99mTc-BN dynamic planar scan showed hot spots in the prostatic fossa in two of the eight patients with cancer, both of whom had a prostate-specific antigen level higher than 20xa0ng/ml. In these patients, high uptake inside the prostatic fossa was detected as early as 1xa0min after injection, before the arrival of radioactivity in the bladder. True positive SPET scans were obtained in all eight patients with cancer. Invasion of the obturator nodes was detected by SPET in three patients, and in all three was confirmed at surgery. Our preliminary data encourage further studies on the prostate with 99mTc-BN. If the high sensitivity of 99mTc-BN SPET is confirmed, this method may play an important role in diagnosing and staging prostate cancer.

Peptide radiopharmaceuticals for diagnosis and therapy.

Abstract. Radiolabelled peptides are an emerging class of radiopharmaceuticals that share chemical and biological properties. From the chemical point of view they have a poly-amino acid structure varying from 3 to more that 200 amino acids, and they are labelled with different isotopes directly or by a linker. Biologically, they bind to specific cell membrane receptors, thus providing in vivo histopathological information for diagnostic purposes, therapy follow-up or targeted radiotherapy. This paper reviews most of the radiolabelled peptides that have been tested in animals and humans in the fields of oncology, neurology, cardiology, inflammation/infection, atherosclerosis and thrombosis. A new classification is also proposed for peptides targeting tumour cells based on the biological function of target receptors. These tailored radiopharmaceuticals are the basis of the new era of molecular nuclear medicine.

Dedicated gamma camera for single photon emission mammography (SPEM)

Prone scintimammography with Tc-99m MIBI has been proposed as a method of detecting breast cancers in women with dense breasts. Clinical reports have shown that this technique lacks sensitivity and specificity for cancers smaller than one cm. This shortcoming is unfortunate, since a patients prognosis is most favorable when her cancer is discovered at an early stage (i.e., when the cancer is less than one cm in size). The authors explored some of the possible causes for the poor performance of prone scintimammography in this population by performing phantom and clinical studies with several different instruments, including a general-purpose gamma camera, a nonimaging germanium detector with excellent energy resolution, and a dedicated high spatial resolution camera for scintimammography (single photon emission mammography, or SPEM) using breast compression. The authors results suggest that unlike X-ray mammography, scatter from extramammary sources plays an important role in breast imaging with radiotracers, and is the dominant effect when imaging near the chest wall. Away from the chest wall, and in conjunction with gentle breast compression (depth less than 7 cm), the energy resolution attained with a dedicated SPEM camera employing cesium iodide crystals appears adequate to differentiate between photopeak and Compton counts, with a Compton-to-photopeak ratio of less than six. The authors preliminary clinical studies suggest that breast compression, good energy resolution and spatial resolution may improve detection of small cancers.

First Results from a YAP:Ce Gamma Camera for Small Animal Studies

The YAP (yttrium aluminum perovskite) camera is a novel gamma camera with intrinsic submillimeter spatial resolution and detection efficiency comparable to a standard Anger camera. At the first stage, it is a miniature gamma camera with a field of view of 4/spl times/4 cm/sup 2/ and is currently utilized for radio tracer studies on small animals. The YAP camera consists of a multicrystal array coupled to a position sensitive photomultiplier tube (Hamamatsu R2486) with a parallel hole collimator. The preliminary results are presented and discussed, in particular the intrinsic characteristics of the scintillating array, which are measured, as well as the position linearity and the spatial resolution, with a parallel collimator. Images were obtained from /sup 99m/Tc line source and nude Balb C mice, which have been injected with /sup 99m/Tc MDP, a bone-seeking agent. The observed images show the importance of the small-field YAP camera in radiopharmaceutical research.

Synthesis, Chemical, Radiochemical and Radiobiological Evaluation of a New 99mTc-labelled Bombesin-like Peptide

A new pentadecapeptide bombesin analogue was prepared by Fmoc synthesis, purified by HPLC and identified by electron ionization mass spectrometry. The biological activity of the new peptide was tested on isolated human colonic muscle cells and compared to native bombesin. Labelling of the new biomolecule with Tc-99m yielded a single radioactive species which remained stable at room temperature for eight hours. In a binding assay, the radiolabelled peptide showed high affinity for oat-cell carcinoma (Kd = 9.8 nM) and colorectal adenocarcinoma (Kd = 27.2 nM). Biodistribution studies, performed in normal rodents, indicated uptake by organs that normally express bombesin receptors, such as liver, intestines and kidneys. Scintigraphic studies, performed in nude mice transplanted with small cell lung carcinoma and colon cancer cells, showed significant tumor uptake two hours p.i. The new synthetic pentadecapeptide appears to have promise for several malignancies, including oat-cell lung carcinoma, colorectal cancer and gastroenteropancreatic (GEP) tumors.

Phase I trial of technetium [Leu13] bombesin as cancer seeking agent: Possible scintigraphic guide for surgery?

Aims and Background Bombesin-like neuropeptides work as neurotransmitters and growth factors at the same time. Several human cancers show overexpression of three receptors for mammalian counterparts of amphibian bombesins (ABNs), ie gastrin-releasing peptide (GRP), neuromedin B (NMB) and possibly another peptide. ABNs in turn are able to bind to mammalian and human receptors in vitro, and it is therefore interesting to study radioisotope-labeled bombesin (BN) and BN-like peptides as cancer seeking agents. Methods and Study Design Starting from the amino acid sequence of [Leu13] ABN, the Demokritos Institute has synthesized and labeled with technetium a new BN-like peptide that has the same biological characteristics as the amphibian peptide; changes were made only in the N-terminal part of this tetradecapeptide. After having obtained satisfactory results with 99mTc BN in a preclinical study, we started a phase I trial involving cancer patients as well as normal volunteers in Tomsk. Three normal volunteers, one patient with small cell lung cancer and one patient with primary prostate cancer were studied after iv injection of 185 MBq, corresponding to 0.7 micrograms of 99mTc BN. Dynamic images of the tumors were acquired for 20 mins, followed by SPET. Total body images were acquired in patients and normal volunteers 1 and 3 h after 99mTc BN acquisition. In addition, 99mTc sestamibi scintigraphy was performed in the patient with small cell lung carcinoma. Results No relevant side effects were observed. Both tumors were well visualized on early 1-2 mins images with planar as well as tomographic imaging. Total body images showed radioactivity in the liver, kidneys and thyroid gland. The stomach and spleen were never imaged. Radioactivity was found in the urinary bladder 4 mins after injection in the patient with prostate cancer. Three-hour total body scans showed radioactivity in the duodenum. In the patient in whom also 99mTc sestamibi scintigraphy was performed, thyroid uptake was much higher with sestamibi than with 99mTc BN, whereas the uptake of small cell lung carcinoma was higher with 99mTc BN than with sestamibi. Conclusions 99mTc BN is able to clearly image tumors with BN receptor overexpression. Our first impression is that in the future this radiopharmaceutical may serve as a cancer seeking agent and, due to its high tumoral uptake, also as a radiotracer for radioisotope-guided surgery.

Detection of sentinel node in breast cancer: pilot study with the imaging probe.

The commonly used gamma probes are easy to use but also give rough information when employed in radioisotope-guided surgery. When images are required for exact localization, a gamma camera as well as a probe have to be used. Position-sensitive photomultipliers have contemporaneously allowed high-resolution scintigraphy and miniaturization of gamma cameras. We have assembled a miniature gamma camera with a 1-square-inch field of view and an intrinsic resolution of about 1 mm. When the minicamera is collimated with a large-holed, highly sensitive collimator, it acquires a spatial resolution of 3 mm. This prototype has been tested in the detection of difficult-to-image breast cancer sentinel nodes. Five nodes that had not been found with the usual technique of an Anger camera plus conventional probe were checked with the miniature camera that we named imaging probe: it actually is small enough to be used as a probe and large enough to give an image. One of the five nodes was found and imaged. It was small, disease-free, close to the tumor and probably hidden by the Compton halo around the peritumoral injection site. Our pilot study shows that the imaging probe, although still a prototype, has certain advantages over conventional methods when lymph node localization is required during surgery.

Small animal imaging by single photon emission using pinhole and coded aperture collimation

The design of detectors for radio-imaging of small animals is challenging because of the high spatial resolution required, possibly coupled with high efficiency to allow dynamic studies. Spatial resolution and sensitivity are difficult to attain at the same time with single photon imaging techniques because collimators define and limit performance. In this paper we first describe a simple desktop gamma imager equipped with a pinhole collimator and based on a pixellated NaI(Tl) scintillator array coupled to a Hamamatsu R2486 PSPMT. The limits of such a system as well as the way to overcome them in future systems is shown next. Better light sampling at the anode level would allow better pixel identification for a higher number of pixels, which is one of the parameters defining image quality and improving spatial resolution. The performance of such a design is compared with other designs using other PSPMT types with different light sampling schemes at the anode level. Finally, we show how the substitution of the pinhole collimator with a coded aperture collimator can result in a substantial improvement in system sensitivity while maintaining very good spatial resolution, possibly at a sub-millimeter level. Calculations and simulations of a particular solution show that sensitivity can improve by a factor of nearly 30.

Erratum to: Peptide radiopharmaceuticals for diagnosis and therapy

It has come to the authors’ attention that two paragraphs were not optimally placed within our occasional survey. The single-sentence paragraph “Insulin-like growth factor-1 (IGF-I) [41] has also shown good uptake on receptor-overexpressing tumour cells.” within the section “G-protein-coupled receptor radioligands” should in fact have been included in the third paragraph within the section “Tyrosine kinase receptor radioligands”. That paragraph should thus have commenced “Insulin-like growth factor-1 (IGF-I) [41] has also shown good uptake on receptor-overexpressing tumour cells. des(1–3)IGF-I, which lacks the N-terminal tripeptide Gly-Pro-Glu....” The subsequent paragraph within the section “G-protein-coupled receptor radioligands”, commencing “The integrin-binding peptide RDG (Arg-Gly-Asp) and related sequences represent a novel class of peptides able to bind to the v3 and v5 integrins...”, should have appeared as the first paragraph in the section “Other peptide radiopharmaceuticals”. We apologise for any confusion that may have been caused.