Giuseppe De Vincentis

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

Abstract. 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 99mTc-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 99mTc-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.

Gastrin-releasing peptide (GRP) analogues for cancer imaging

Small neuropeptides, labeled with gamma- and/or beta-emitting radionuclides, are currently being investigated for their ability to bind to cell-surface receptors, overexpressed in a wide variety of malignant tissues being, thus, potentially useful for radionuclide detection and/or therapy for tumors. Particular attention has been focused on the amphibian peptide, bombesin (BN), and the molecularly related gastrin-releasing peptide (GRP). These peptides act as neurotransmitters and endocrine cancer cell-growth factors on normal tissues as well as on neoplastic cells of various origin. In recent investigations, modification of the native peptide structure has been attempted in order to obtain derivatives, which might easily be labeled with radionuclides. Thus, iodinated (I-125) BN derivatives, as well as Indium (In-111) labeled BN analogs are currently being investigated, presenting satisfactory tumor localization. Also, some new BN analogs containing a 6-carbon linker have been prepared and labeled with Rhenium-188, resulting in positive in vitro binding to prostate cancer cells. More recent studies refer to the Technetium-99m labeling of BN, performed either directly, after attaching proper technetium-chelating groups onto the BN sequence, or indirectly, by coupling BN to a preformed 99mTc-tagging ligand. Both types of conjugates were found to have a high in vitro affinity for cells with BN receptors, also presenting satisfactory in vivo uptake in experimental tumor models. Pilot clinical studies of a new BN-derived, 99mTc-labeled pentadecapeptide indicated significant uptake by breast cancer and invaded lymph nodes, as well as by prostate cancer, small-cell lung carcinoma, gastro-entero-pancreatic tumors, and others, Further studies of this new GRP derivative, as well as of other new BN-like peptides, are intensively performed internationally today.

Role of 99mTc-bombesin scan in diagnosis and staging of prostate cancer.

Aim of this work was to asses whether a novel 99mTc labeled Bombesin (BN) can play a clinical role in diagnosis and staging of prostate cancer. 14 patients were studied with trans-rectal ultrasonography-guided biopsy, CT and MRI and with 99mTc BN Scintigraphy. Five patients were also imaged by 111In Octreotide (O) scan. All the patients but one were submitted to surgery and final diagnosis was reached by pathology, taken as the gold standard method. Two patients showed benign adenoma and 12 patients showed cancer at biopsy. 99mTc BN SPECT was positive in all 12 patients with cancer. Four of these patients also showed pelvic focal uptake, referred to inguinal lymph-nodal involvement. MRI and CT provided similar findings in only three cases. Pathologic evaluation after operation confirmed the invasion of nodes in all four subjects. Both 99mTc BN and 111In O scans provided normal findings in the two subjects affected by benign adenoma, while 111In O was positive in only two of three patients with cancer and was always unable to detect nodal invasion. These preliminary data suggest that 99mTc BN SPECT scan could be useful to detect primary prostate cancer and to reveal loco-regional node involvement.

Detection of colon cancer with 99mTc-labeled bombesin derivative (99mTc-leu13-BN1)

Breast, prostate, and lung cancer have been successfully detected with 99mTc bombesin (99mTc-leu13-BN1), the radiopharmaceutical that our group developed from synthesis to diagnostic trials. Overexpression of bombesin receptors (BNRs) in colon cancer is well known: the aim of this study was to assess whether or not colon cancer can be detected with a 99mTc-leu13-BN1 scan. Thirteen (13) patients, 7 of whom with known rectal cancer and 6 scheduled to undergo endoscopic removal of polyps for suspicion of colon cancer, were studied with a 99mTc-leu13-BN1 scan. Dynamic, single photon emission computed tomography, and whole-body scans were performed within 1 hour, before discharge of radioactivity from the liver into the duodenum. Sixteen (16) of 17 colorectal cancer locations were detected with a 99mTc-leu13-BN1 scan with 94.1% sensitivity. Six (6) lesions were benign: 1 Crohns disease, 1 polyp with mild dysplasia, 4 polyps with simple hyperplasia; 99mTc-leu13-BN1 scans were positive in two nontumoral lesions, Crohns disease, and mild dysplasia and true negative in 4: specificity was 67%. Of the 7 patients with known rectal cancer, 5, who underwent operations instead of radiation therapy, showed lymph-node invasion on 99mTc-leu13-BN1 scans. Operations confirmed the scintigraphic staging. 99mTc-leu13-BN1 is taken up by colon cancer. Scans are sensitive, although scarcely specific. 99mTc-leu13-BN1 allows for node-invasion detection.

Autoradiographic localization of [3H]muscimol binding sites in rat stomach: evidence for mucosal GABAA receptors

The distribution in the rat stomach of specific [3H]muscimol binding sites, which show characteristics of GABAA receptors, was examined by light microscopic autoradiography. Silver grains representing specific binding were present both in the antrum and body, with highest densities in the muscle layers. A small fraction of the binding was confined to gland cells of the mucosa in the gastric body, rather than in the antrum. The label was not specifically concentrated at the myenteric ganglia. These findings, along with earlier data, suggests that the local GABA content may regulate not only the contractility, but also the secretory functions of the stomach via gastric GABAA receptors.

Early detection of coronary artery disease by 64-slice multidetector computed tomography in asymptomatic hypertensive high-risk patients

BACKGROUND The 64-slice multidetector-row computed tomography (MDCT) is an accurate noninvasive technique for assessing the degree of luminal narrowing in coronary arteries of patients with chronic ischemic disease. Aim of this study was to determine the value of MDCT in comparison to invasive coronary angiography (ICA) for detecting the presence and extent of coronary atherosclerotic plaques in a population of asymptomatic, hypertensive patients considered to be at high risk for cardiovascular events. METHODS We studied 67 asymptomatic, hypertensive patients at high-risk (Euro Score >5%). All patients had negative or nondiagnostic findings at exercise stress testing and therefore underwent both MDCT and ICA. RESULTS In the per-patient analysis, MDCT correctly identified 16/17 (94%) patients with significant coronary artery disease involving at least 1 vessel and 48/50 (96%) normal subjects. In the per-segment analysis, MDCT correctly detected 21/22 (95%) coronary segments with a stenosis >or=50% and 856/868 (98%) normal segments, with a high negative predictivity of normal scans (100%). There was a good concordance between MDCT and ICA, with a high Pearson correlation coefficient between the coronary narrowings with the two techniques (r=0.84, p<0.01). Mean coronary calcium score was higher for the 17 patients with significant coronary artery disease on ICA than in the 50 patients without (422+/-223 HU vs 72+/-21 HU p<0.001). The ROC curves identified 160 as the best calcium volumetric score cut-off value able to identify >or=1 significant coronary stenosis with sensitivity 88% and specificity 85%. CONCLUSIONS MDCT is an excellent noninvasive technique for early identification of significant coronary stenoses in high risk asymptomatic hypertensive patients and might provide unique information for the screening of this broad population.

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.

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.99m Tc 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.

New devices for imaging in nuclear medicine.

Pinhole gamma camera imaging offers the ability to obtain high resolution images from single gamma ray emitting radiotracers playing a reasonable tradeoff between very small field of view (FoV) and sensitivity. On the other hand the total spatial resolution of a pinhole imaging device is predominantly affected by the detector intrinsic spatial resolution for reduced magnification factors. To design very compact pinhole SPET scanners with very high intrinsic spatial resolution, authors investigated a miniature gamma camera based on the newly developed Hamamatsu H8500 flat panel photomultiplier. The PSPMT was coupled to the following scintillation arrays: CsI(Tl) array with 0.2-mm, 1-mm, 1.4-mm pixel size and NaI (Tl) with 1-mm pixel size. The imaging performances were evaluated by 57Co spot and flood irradiations. NaI(Tl) array shows a better pixel identification for 1 mm pixel size, proving to be a good candidate to make a large area photodetector based on multi PSPMTs closely packed. Although CsI(Tl) array had the smallest pixel size, the low light output limited the best intrinsic spatial resolution to about 0.5 mm.

Slow coronary flow and stress myocardial perfusion imaging. Different patterns in acute patients.

Objective We investigated myocardial perfusion in acute patients with slow coronary flow (SCF) at angiography. Whether impaired myocardial perfusion occurs in acute patients with SCF is unknown. Methods We enrolled 28 consecutive patients with SCF in the epicardial coronary arteries with no evidence of significant stenosis. SCF affected a single coronary artery in 14 patients (group A) and all three coronary vessels in 14 others (group B). Coronary angiography was repeated after dipyridamole infusion and single photon emission computed tomography was performed using dipyridamole as the stress agent. The Thrombolysis in Myocardial Infarction frame count was measured in SCF vessels at baseline and after dipyridamole infusion. Results Mean Thrombolysis in Myocardial Infarction frame count significantly decreased after dipyridamole in both groups. At baseline, mean values of the single photon emission computed tomography score were 31.5 ± 1.6 and 25.1 ± 2.1 in groups A and B, respectively. After dipyridamole, they increased from 31.5 ± 1.6 to 37.8 ± 1.4 (P < 0.001) in group A, whereas a further decrease to 15.0 ± 1.2 (P < 0.005) was observed in group B. Conclusions An opposite behavior of myocardial perfusion was observed after dipyridamole infusion: a normal response in patients with SCF affecting one single coronary artery versus an ischemic-like response in those with CSF affecting all three coronary arteries.