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Biomedical subjects

G De Vincentis

Publications and source records attributed to G De Vincentis.

At least 19 recordsLinked to original sources

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.

Animals↗

Technetium labeled bombesin-like peptide: preliminary report on breast cancer uptake in patients.

Bombesin-like peptides are neurotransmitters and cancer growth factors. Several tumors, breast cancer among them, show one or more than one of the three known bombesin receptors. We have synthesized and labeled with technetium 99m a new pentadecapeptide, analogue to the leu13 amphibian bombesin (99mTc BN). Labeling yield was 83 +/- 4%. Prone Scintimammography was performed on five patients affected by breast cancers (T categorization: two T1b and three T1c), after injecting 0.7 mg, 185 to 296 MBq (5 to 8 mCi) of the peptide. Total body scan did not show free technetium biodistribution. No adverse reaction was observed. Prone Scintimammography with 99mTc Sestamibi (99mTc SM) was also performed few days later. 99mTc BN detected all 5 cancers, whereas 99mTc SM only four: all the T1c and one T1b cancer. Two of them showed axillary node invasion that was detected by both the radiotracers. A fibroadenoma present on contralateral breast to the one with cancer, was not detected neither by 99mTc SM nor by 99mTc BN. Tumor/breast normal tissue ratio (T/B) was constantly higher with 99mTc BN than with 99mTc SM. Maximal T/B was measured as 1.79 with 99mTc SM and 2.25 with 99mTc BN 5 min after fast i.v. administration. In conclusion our 99mTc BN is taken up by primary breast cancer showing higher T/B than 99mTc SM (p < 0.01). In our limited scale, 99mTc BN appears to be safe and, in our limited scale, even more accurate than 99mTc SM for detecting breast cancer.

Aged↗

High-resolution scintimammography improves the accuracy of technetium-99m methoxyisobutylisonitrile scintimammography: use of a new dedicated gamma camera.

The main disadvantage of technetium-99m methoxyisobutylisonitrile (MIBI) prone scintimammography is its limited sensitivity for T1a and T1b cancers with a size of less than 1 cm. We have developed a high-resolution scintimammographic technique using a gamma camera based on a new concept, namely a position-sensitive photo-multiplier tube. The field of view of this camera, previously known as the SPEM (single photon emission mammography) camera, was 10 cm diameter. Scintimammographic images were acquired in the axial view; each breast was compressed to a thickness of 3-6 cm, modal class 4 cm. When the compressed breast was larger than the field of view, more than one study was performed in order to image the entire gland. Fifty-three patients were studied with high-resolution-scintimammography (HRSM) and Anger camera prone scintimammography (ACPSM). HRSM was performed 70 min after i.v. administration of 740 Mbq of (99m)Tc-MIBI; ACPSM images were acquired 10 and 60 min following the injection. Early 10-min ACPSM images were only evaluated for routine diagnostic purposes, while comparison was carried out between the 60-min ACPSM and 70-min HRSM images. At fine-needle aspiration (FNA) and/or open biopsy, 31 patients showed cancer: 15 T1c, 11 T1b and 5 T1a. In T1a-T1b cancers, the sensitivity of scintimammography was 50% with ACPSM and 81.2% with HRSM (P<0.01). Specificity was 86% with both techniques. HRSM is a promising new technique that improves the sensitivity of (99m)Tc-MIBI scintimammography in tumours sized less than 1 cm without apparently reducing its specificity. We are now working on a larger field-of-view camera.

Aged↗

Recovery of contractility of viable myocardium during inotropic stimulation is not dependent on an increase of myocardial blood flow in the absence of collateral filling.

OBJECTIVES: The purpose of this study was to determine whether contractile recovery induced by dobutamine in dysfunctioning viable myocardium supplied by nearly occluded vessels is related to an increase in blood flow in the absence of collaterals. BACKGROUND: Dobutamine is used to improve contractility in ventricular dysfunction during acute myocardial infarction. However, it is unclear whether a significant increase in regional blood flow may be involved in dobutamine effect. METHODS: Twenty patients with 5- to 10-day old anterior infarction and > or =90% left anterior descending coronary artery stenosis underwent 99mTc-Sestamibi tomography (to assess myocardial perfusion) at rest and during low dose (5 to 10 microg/kg/min) dobutamine echocardiography. Rest echocardiography and scintigraphy were repeated >1 month after revascularization. Nine patients had collaterals to the infarcted territory (group A), and 11 did not (group B). RESULTS: Baseline wall motion score was similar in both groups (score 15.9+/-1.3 vs. 17.4+/-2.0, p = NS), whereas significant changes at dobutamine and postrevascularization studies were detected (F[2,30] = 409.79, p < 0.0001). Wall motion score improved significantly (p < 0.001) in group A both at dobutamine (-5.3+/-2.2) and at postrevascularization study (-5.5+/-1.9), as well as in group B (-3.9+/-2.8 and -4.5+/-2.4, respectively). Baseline 99mTc-Sestamibi uptake was similar in both groups (62.9+/-9.7% vs. 60.3+/-10.4%, p = NS), whereas at dobutamine and postrevascularization studies a significant change (F[2,30] = 65.17, p < 0.0001) and interaction between the two groups (F[2,30] = 33.14, p < 0.0001) were present. Tracer uptake increased significantly in group A both at dobutamine (+ 10.9+/-7.9%, p < 0.001) and at postrevascularization study (12.1+/-8.7%, p < 0.001). Conversely, group B patients showed no change in tracer uptake after dobutamine test (-0.4+/-5.8, p = NS), but only after revascularization (+8.8+/-7.2%, p < 0.001). CONCLUSIONS: The increase in contractility induced by low dose dobutamine infusion in dysfunctional viable myocardium supplied by nearly occluded vessels occurs even in the absence of a significant increase in blood flow.

Adult↗

Role of 99mTc-Sestamibi scintimammography by SPEM camera in the management of breast cancer in the elderly.

The incidence of breast cancer in the elderly is 10 fold higher than in the population younger than 65 years. Moreover, in this segment of the population there are not defined clear practice guidelines regarding patient management. X-ray mammography, the most widely used diagnostic technique, is often inadequate to differentiate benign from malignant lesions. 99mTc Sestamibi scintimammography plays an important role as complement to mammography; in fact it is a very sensitive and specific method for breast cancer detection, when cancers > 1 cm diameter are considered. However, sensitivity values fall to 50-60% in the case of small tumors (T1a and T1b). In this study we present the results of a new Small Field Of View (SFOV) Gamma Camera with very high spatial resolution that allows the first Single Photon Emission Mammography (SPEM). Eighteen patients aged 71 +/- 6 years with mammographically detected breast lesions were submitted to a Prone Scinti Mammography (PSM) by conventional Gamma Camera and to a SPEM on craniocaudal view. A final diagnosis was reached by histopathology. SPEM correctly diagnosed 15 of 16 cancers, while PSM was not able to recognize 5 malignant lesions with subcentimeter size. Both the techniques provided normal findings in the case of benign lesions. The 99mTc Sestamibi scintimammography, particularly when performed by SPEM camera, is a sensitive, specific, and non invasive method to define the nature of radiologically described breast masses and would be very useful as a complement to X-ray mammography in screening programs for breast cancer.

Aged↗

99mTc MIBI prone scintimammography in patients with suspicious breast cancer: relationship with mammography and tumor size.

99mTc MIBI prone scintimammography (PSM) is reported to be a specific examination in order to assess the nature of breast lesions. Fifty-three patients whose mammography was stratified according to the breast imaging reporting and data system (BI-RADS), the five category classification of mammography approved by the American college of radiology, were studied with prone scintimammography, with the aim of assessing the accuracy of this exam and its usefulness in clinical practice. Thirty-five out of forty-one patients with BI-RADS category V (high probability of cancer) showed cancer at histology. Thirty-one of them had positive PSM. Three out of the six patients with mammo-graphic features of category IV indicated malignancy. PSM was positive in all of them and negative in the three benign lesions. One of the five patients with category III mammography showed cancer and positive PSM. The PSM was negative in 12/13 patients with benign patology (specificity 92.3%). When the cancers were stratified for T-category significant differences were found between the sensitivity for tumors larger or smaller than 1 cm. The sensitivity was 50% for the cancers smaller than 1 cm and 96.9% for those larger than 1 cm. PSM is a very specific method to determine the nature of breast lesions. Its sensitivity is also high but has to be improved when tumors smaller than 1 cm have to be detected. From a clinical point of view PSM can at the moment be considered as an accurate method for the study of borderline lesions of IV and also of III BI-RADS category. In this case a positive PSM indicates an impact in clinical decision making.

Breast Diseases↗

Scintigraphic imaging of hepatic epithelioid hemangioendothelioma.

The epithelioid hemangioendothelioma of the liver has been recently characterized as a rare tumor with distinctive pathological features affecting young adults. Our report describes a case of histologically confirmed primary epithelioid hemangioendothelioma of the liver, diagnosed by clinical examination as well as radiological (CT/MR) and scintigraphic imaging (labelled red cells/ phytate-SPECT). This case highlights the usefulness of nuclear medicine techniques during the diagnostic of this rare tumor. Further it stresses the possibility of employing an easy and noninvasive method to adequately follow-up those patients who cannot be considered as disease-free even after orthotopic liver transplantation because of the recurrence of the disease in the transplanted liver.

Diagnostic Imaging↗

99mTc anti-D-dimer MoAb detects venous thrombi in man.

Authors' work is based on the ability of a 99mTc labelled antibody (MoAb) against D-Dimer (D-D) to visualize thrombi in man. D-Dimer is a specific epitope created during the cross-linking process of fibrin strains. Five normal volunteers and 5 patients with leg varices were given 10 mCi of 99mTc anti-D-Dimer MoAb (research approved by our Ethical Committee). Each patient gave his informed consent. Scintigraphic images were taken at 5, 60, 180 min. No adverse reaction was observed. Two patients underwent saphenous stripping 3 hrs after injection, in the other 4 patients scintigraphic images were acquired at 6 and 8 hrs. Twelve hot spots were visualized. Of these, 5 were localized during operation with a pencil-like probe and exsected. Specific activity of exsected thrombi, saphenal walls and blood samples was measured. Thrombus to vein wall ratio of 2.2 +/- 0.6 and a thrombus to blood of 3.1 +/- 0.8 was measured. In non operated patients the best scintigraphic images were obtained between 60 and 180 min. 99mTc anti-D-Dimer MoAb is a promising agent for localization of thrombi.

Antibodies, Monoclonal↗

Inhaled nitric oxide in patients with severe heart failure: changes in lung perfusion and ventilation detected using scintigraphy.

Inhaled nitric oxide (NO) is a selective pulmonary vasodilator in patients with end-stage cardiac failure. Preoperative high pulmonary vascular resistance could modify early and late results after heart transplantation generally due to right-ventricular failure. Aim of this study was to assess pulmonary vascular resistance variability following inhalation of NO by using a scintigraphic method. Our preliminary results suggest that inhaled NO in patients with end-stage heart failure redistributes blood away from apical regions and towards more basal and posterior segments, probably dilating blood vessels in ventilated but nonperfused zones. NO may represent a simple and reliable method to evaluate dynamic response of pulmonary vasculature.

Administration, Inhalation↗

Preliminary evaluation of the usefulness of Tc-99m (V) DMSA in pancreatic neuroendocrine tumors.

The authors describe the possible application of Tc-99m (V) DMSA scintigraphy in pancreatic neuroendocrine tumors. In consideration of the common embryonic origin of these tumors and other neoplastic diseases (medullary thyroid carcinoma, pheocromocytoma, neuroblastoma) that have been well studied with radionuclide imaging, five cases of pancreatic neuroendocrine tumors (two insulinomas, one vipoma, and two unclassified neuroendocrine tumors) were successfully visualized with Tc-99m (V) DMSA scintigraphy, thus giving an overall "imaging confirmation" of the histologic and/or cytologic results in terms of primary and metastatic localization. The authors point out the importance of their results, obtained in a simple and repeatable manner, and suggest a real comparison in this setting between this approach and octreotide scintigraphy.

Female↗

Muscular uptake of Tc-99m MIBI and TI-201 in Duchenne muscular dystrophy.

Lack of dystrophin, a protein localized to the inner surface of the sarcolemma of the muscle fiber, is the cause of Duchenne type muscular dystrophy. Plasma membrane damage of the muscular fiber occurs, followed by Ca++ influx into the fibers. There is severe mitochondrial damage in dystrophic but still viable fibers. Five children aged 5-7 years were studied with MRI, TI-201, and Tc-99m sestamibi scintigraphy of the thighs. These three methods showed that the sartorius is the least damaged muscle in Duchenne type muscular dystrophy. MRI showed mild damage of adductors and quadriceps; TI-201 scintigraphy showed a marked reduction of radioactivity in the same muscles; Tc-99m sestamibi uptake occurred only in the sartorius muscle; the quadriceps was not imaged and adductors showed a faint image. A decrease of water in muscular fibers as well as fatty fibrous substitution, occurs after death of the fibers, whereas plasma membrane and mitochondrial damage reduced the uptake of tracers when the fiber is still viable. The interesting mismatch between sestamibi and TI-201 can be explained by considering that the cellular mechanism of uptake and retention of Tc-99m sestamibi involves both plasma membrane and mitochondria, whereas the uptake of TI-201 is only affected by plasma membrane damage.

Child↗

Myocardial scintigraphy with 99mTc-sestamibi in children with Kawasaki disease.

Kawasaki disease (KD) is a systemic vasculitis syndrome of early childhood. It involves particularly the coronary arteries and may cause aneurysms and thrombotic occlusions. Echocardiography is the most useful method of detecting coronary aneurysms. Nevertheless, obstructive lesions are difficult to evaluate and often need invasive coronary angiography. An important feature of this disease is the possibility of finding coronary pathology several years after the onset. This characteristic makes KD an important cause of coronary artery disease (CAD) in young adults. Thus patients with KD and previously diseased coronary arteries should be kept under long-term control. However, coronary angiography is invasive and cannot be performed repeatedly, especially in young patients. As an alternative, thallium 201 scintigraphy has been employed, but its low-energy photons are suboptimal for standard gamma-camera imaging, particularly in children aged less than three years. To verify the usefulness of a noninvasive assessment of myocardial perfusion, the authors used rest and dipyridamole 99mTc-Sestamibi scan in 15 children (ranging from one to six years of age) with Kawasaki's cardiac involvement. Coronary aneurysms have been demonstrated by echocardiography in 12 patients; 8 patients were also submitted to cardiac catheterization. The sensitivity of 99mTc-Sestamibi imaging for detection of overall coronary lesions was 88% and the specificity was 93%. These data suggest that rest/dipyridamole 99mTc-Sestamibi scintigraphy is an accurate and noninvasive method for the detection and follow-up of Kawasaki's cardiac damage even in patients aged one year.

Child↗

99Tcm-MIBI uptake in green plants.

Uptake of 99mTcm-sestamibi by biological structures depends on delivery and concentration by electrochemical gradients through the biological membranes and can be simply studied using a green plant model in which photosynthesis tightly modulates water and solute regional flow. Photosynthesis creates electrochemical gradients inside chloroplasts and mitochondria. Moreover, it is the driving force for the movement of water and solutes through induction of pore opening which causes capture of CO2 and loss of water vapour. Thus osmotic pressure increases thereby drawing water from the roots. Hypoestes sanguinolenta was used as an experimental model. This plant displays green zones (with several chloroplasts) and red zones (where they are absent). To detect the uptake differences between these zones we used a new, high-resolution gamma camera. Our results show that (a) 99mTcm-sestamibi is actively transported with water and ions by xylem to leaves where it may diffuse at cellular levels; (b) activation of photosynthesis by light strongly influences the total uptake and the selective compartmentation in green zones; and (c) the green plant's particular physiology tremendously enhances the differences between 99Tcm-sestamibi and 201Tl uptake. We suggest that viable cells, able to create and maintain electrochemical gradients, selectively take up 99Tcm-sestamibi.

Biological Transport↗

Changes in glutathione content and localization in rat heart as a function of age.

The influence of aging on glutathione levels and distribution in the heart was studied in male Sprague-Dawley rats of 3 (young), 12 (adult) and 24 (old) months of age using biochemical and histofluorescence techniques, respectively. Biochemical assays of reduced glutathione (GSH) in the right and left ventricles and in the septum showed a significant decrease in GSH levels in adult in comparison with young animals. No further changes were noticeable between adult and old rats. GSH histofluorescence revealed a rather homogeneous distribution of the product of histochemical reaction within both right and left atria in 3-month-old rats. In 12-month-old rats a reduction of GSH histofluorescence in comparison with younger animals was noticeable. The loss is more consistent in the epicardial portion of the right atrium and in the endocardial region of the left atrium. In the atria of 24-month-old rats GSH reactivity was homogeneously distributed throughout the atrial wall and was significantly lower than in young or adult rats. In 3-month-old rats GSH histofluorescence was slightly lower in the epicardial than in the endocardial portions of both ventricles. In adult rats a significant decrease of GSH histofluorescence was noticeable in comparison with 3-month-old rats. The loss is particularly pronounced within the endocardial region of the left ventricle. In 24-month-old rats GSH histofluorescence showed no significant differences between adult rats. However, GSH was more homogeneously distributed throughout the ventricular wall than in adult animals. The significance of these data is discussed in relation to the role that GSH plays in protecting the myocytes against free radical damage.

Aging↗

Vasoactive intestinal polypeptide receptors in rat cerebral vessels: an autoradiographic study.

1. Localization and pharmacological properties of the vasoactive intestinal polypeptide (VIP) receptors in rat circle of Willis arteries and in the arteries of pial-arachnoid membrane were studied using light microscope autoradiography combined with radioreceptor binding techniques. 2. [125I]-VIP was specifically bound to sections of rat cerebral arteries with a dissociation constant value of 0.5 nM and a binding site density of 80 fmol mg protein-1. Radioreceptor binding experiments revealed that the binding characteristics of [125I]-VIP were consistent with the labelling of specific VIP receptors. The rank order of potency of various substances tested to inhibit [125I]-VIP binding was the following: VIP greater than peptide histidine methionine greater than secretin greater than glucagon. 3. Light microscope autoradiography revealed the localization of [125I]-VIP binding sites in the medial layer of circle of Willis and pial arteries. Quantitative determination of [125I]-VIP binding site density in the different circle of Willis arteries demonstrated a higher accumulation of silver grains in the anterior than in the posterior cerebral arteries. Pial arteries are richer in VIP receptor sites than circle of Willis arteries. 4. These results suggest that the physiological neurogenic vasodilation elicited by VIP on cerebral arteries is mediated by the interaction with specific receptor sites located primarily within cerebral vessels structures involved in the control of cerebrovascular resistances.

Animals↗