Dimorphic distribution of the two main GABA(A) binding sites in cortical and limbic areas of a rodent living in natural environmental conditions.

Labeling of the two more important gamma-aminobutyric acidA (GABA(A)) supramolecular sites with [3H] muscimol (GABA(A)) and [3H] flunitrazepam (benzodiazepine) provided saturable, stable, and dimorphic binding activities in cortical and limbic regions of the wood mouse Apodemus sylvaticus. Of the cortical layers, which contained the highest [3H] muscimol binding levels, only the female lamina V supplied a greater (51%; P <0.01) receptor density than in the male. Areas of the limbic system instead proved to be the more favorable targets for differential GABA(A) binding levels. The highest (P <0.001) and higher levels were found in the oriens-pyramidalis CA1 layer of the hippocampus (65%) and in the vertical limb diagonal band-medial septal nucleus (48%), basolateral amygdala nucleus (45%), and ventromedial hypothalamic nucleus (43%), respectively, of the female. A similar pattern was obtained for [3H]flunitrazepam binding activity, especially in the presence of GABA. The highest and higher binding activities were obtained in the female central amygdala nucleus (78%) and in the ventromedial hypothalamic nucleus (52%), basolateral amygdala nucleus (48%), and oriens-pyramidalis CA1 layer of the hippocampus (47%), respectively, whereas higher levels were observed only in the male vertical limb diagonal band-medial septal nucleus (56%). Even in the cortical regions, the female exhibited higher (42%; cortex lamina V) and moderately higher (38%; cortex lamina VI) levels, with binding differences in the latter site plus in the basolateral amygdala nucleus occurring in a GABA-nondependent manner. From the saturation binding analyses it was possible to reveal that both maximal number of binding sites (Bmax) and mean dissociation constant (K(D)) modifications were responsible for receptor differences of the two GABAergic sites. These findings tend to suggest that dimorphic variations of the GABA(A) supramolecular sites, in some cortical and limbic regions, are strongly involved in sex-specific aggressive and reproductive activities of rodents living in their natural habitats.

Immunoscintigraphy of atherosclerotic uncomplicated lesions in vivo with a monoclonal antibody against D-dimers of insoluble fibrin.

To test the effectiveness of a new F(ab')2 monoclonal antibody against human fragment D-dimer of cross-linked fibrin in the detection of uncomplicated atherosclerotic lesions of the carotid vessel previously documented at echo-color-Doppler and selective arteriographic study, 8 patients underwent a scintigraphic study including dynamic and early and delayed (3 h later) static imaging of the neck after injection of a bolus of 99mTc-labeled monoclonal antibody, and were subsequently operated. Vessel specimens and blood samples were drawn at operation and counted. No adverse reaction occurred after administration of the monoclonal antibody. The atherosclerotic lesion appeared as a focal area of asymmetrical tracer uptake, already visible at early images in four patients, and at delayed images in five. The average tracer uptake ratio between pathological and normal vessels was 1.40+0.24 (P < 0.05) at time-activity curves derived from dynamic images, 2.17+/-0.97 (P < 0.05) at early static images and 2.05+/-0.98 (P < 0.05) at delayed static images, respectively. Mean vessel to blood uptake rate of specimens obtained at operation was 2.22+/-0.59 (P < 0.001). The study shows that the 99mTc-labeled antibody was found to be safe and capable of detecting atherosclerotic plaques in humans.

SPECT improves accuracy of somatostatin receptor scintigraphy in abdominal carcinoid tumors.

UNLABELLED: Abdominal carcinoid tumors are often small and difficult to localize. Somatostatin receptors have been detected in carcinoids, thus enabling their in vivo visualization by scintigraphy with 111In pentetreotide, a radiolabeled somatostatin analog. The aim of this study was to determine the value of 111In-pentetreotide SPECT in the detection of abdominal carcinoids and to compare these results with the outcomes from planar scans and conventional imaging techniques. METHODS: Eighteen patients with a present, or previously operated, abdominal carcinoid were evaluated. Abdominal SPECT scans were acquired 4 hr postinjection of 111In-pentetreotide and multiple planar views were performed at 4, 24, and 48 hr. RESULTS: No adverse reactions were observed after radiopharmaceutical injection. In 13 of 18 patients, abnormal sites of uptake were found by SPECT, which localized 9 abdominal extrahepatic lesions (in 7 patients) and 33 hepatic lesions (in 10 patients). No pathologic accumulation was seen in the five patients considered in complete remission after surgery. Planar scans visualized 5 abdominal extrahepatic sites (in 4 patients) and 21 liver tumor sites (in 7 patients), while conventional procedures detected 3 abdominal extrahepatic lesions (in 2 patients) and 30 hepatic lesions (in 7 patients). CONCLUSION: Indium-111-pentetreotide scintigraphy is a safe and practical procedure. SPECT appears to be more sensitive than planar scintigraphy and conventional methods to detect abdominal carcinoids; it can increase the number of visualized tumor sites and that of patients with positive findings and may therefore have a role not only in the mapping of tumor spread but also in therapeutic decisions.

The in-vitro transformation of [3H]dehydroepiandrosterone into its principal metabolites in the adrenal cortex of adult castrated male rats and following steroid treatment.

The adrenal gland of castrated adult male rats metabolized [3H]dehydroepiandrosterone in vitro to delta 4-androsten-3,17-dione (4AD), testosterone, dihydrotestosterone (DHT) and 5 alpha-androstane-3,17-dione (5 alpha AD). Despite the low testosterone values, DHT and 5 alpha AD were higher 30 and especially 60 days after castration, with raised 4AD:testosterone and decreased testosterone:DHT ratios. The 5 alpha-reductase activity thus appears to increase with time after castration. Fourteen days after castration, 4AD was the only metabolite that was raised compared with intact animals, and testosterone was comparable in sham-operated and castrated rats. The administration of testosterone propionate to castrated rats restored testosterone values to those of intact rat adrenals, whereas 4AD values were greater. The administration of dihydrotestosterone propionate also yielded higher levels of 4AD, in the presence of a lower testosterone value. After administration of oestradiol benzoate, 4AD values were lower especially compared with the other hormone-treated groups, and there was an unexpectedly high testosterone value. These data indicate that the adrenal gland contributes to the production of androgens, as previously noted by Andò, Canonaco, Beraldi et al. (1988) who showed increased plasma 4AD and testosterone levels in adult male rats 30 days after castration. Furthermore, adrenal androgen production in castrated animals is differentially regulated by sex steroids.

Differential modulation of [3H]flunitrazepam binding in female rat brain by sex steroid hormones.

Quantitative autoradiographic analysis revealed changes in [3H]flunitrazepam (a benzodiazepine agonist) binding in the anterior hypothalamus nucleus, the medial preoptic area and the cortico-medial amygdala nucleus following in vivo estradiol. The administration of 4 mg of progesterone, but not 1 mg, increased the binding of [3H]flunitrazepam in the basolateral amygdaloid nucleus and in the oriens-pyramidalis CA1 layer of the hippocampus. Exposure of brain sections in vitro to the potent, naturally occurring progesterone metabolite, 3 alpha-hydroxy-5 alpha-dihydroprogesterone, induced GABA-dependent changes in flunitrazepam binding, similar to the changes induced by progesterone, thus suggesting that different steroid mechanisms are implicated in the control of flunitrazepam binding.

The neuroanatomic binding pattern of [125I]atrial natriuretic factor in the Japanese quail brain.

Application of quantitative autoradiography technique provided a discrete anatomical distribution pattern of the atrial natriuretic factor (ANF) in the Japanese quail, Coturnix coturnix japonica, brain. The highest binding levels of [125I]ANF were shown to occur in telencephalon areas, such as fasciculus diagonalis Brocae (232 fmol/mg protein), septum (194 fmol/mg protein) and olfactory bulb (153 fmol/mg protein), and in posterior sites, such as nucleus interpeduncularis (177 fmol/mg protein), while lower levels (> 51 < 87 fmol/mg protein) were found in the hypothalamic sites of the diencephalon. The similar ANF receptor density levels in some brain areas of the quail as well as both mammalian and non-mammalian species suggest that this peptide might be involved in osmoregulatory activities (at the brain level) and furthermore indicate a probable functional conservation of ANF in vertebrates.

Sexual dimorphism of GABAA receptor levels in subcortical brain regions of a woodland rodent (Apodemus sylvaticus).

This is the first report of quantitative autoradiography results showing sex differences of GABAA receptor levels in brain regions of a wild rodent (wood mouse, Apodemus sylvaticus) living in its natural habitat. The labeling of this GABAergic site with its specific high affinity radioligand [3H] muscimol provided a heterogeneous and dimorphic binding pattern in some of the neural centers. In the female, higher (> or = 50 < or = 65%) to moderately higher (< 50%) binding levels than in the male, even after correction of the specific binding values using the calculated quenching coefficients, were observed in the substantia nigra pars reticulata and ventral lateral thalamic nucleus, brain centers that are relays of motor circuits. In the male, on the other hand, a higher level was only obtained in the caudateputamen. Relays of the stria terminalis-hypothalamic-central gray pathway such as the bed nucleus of the stria terminalis, the pontine central gray and the ventromedial hypothalamic nucleus, were among the other female brain areas with an extremely higher (> 65%) to higher and moderately higher binding activity than in the male. From the saturation analyses, it appeared that the binding differences were mainly due to Bmax variations, although closer examinations revealed that changes in the KD might have also accounted for [3H] muscimol binding differences, as shown by the high KD and Bmax values in the bed nucleus of the stria terminalis, the substantia nigra pars reticulata and the pontine central gray of the female wood mouse. These findings suggest that the dimorphic binding activity of GABAA receptors in the above brain regions might be involved in neuronal circuitry mechanisms related to sex-specific social behaviors in rodents living in their natural environmental conditions.

Gonadal-GABAergic interaction is an important factor involved in photoperiod-induced 2-[125I] iodomelatonin binding changes in the Japanese quail brain.

The type of mechanism(s) by which melatonin alone and/or through the intervention of other putative neurotransmitters is able to control circadian rhythms remains unresolved. Comparison of 2-[125I]iodomelatonin binding pattern in the brain of castrated and gonadally intact Japanese quail (Coturnix japonica), using quantitative receptor autoradiography, displayed that the combination of the intact gonadal condition and a long-day (16L:8D) photostimulatory schedule is responsible for major binding changes. In fact, high and low binding levels were obtained in the suprachiasmatic area and nucleus ectomamillaris (p < 0.01) and in the nucleus preopticus anterior and paleostriatum primitivum (p < 0.001), respectively. A gonadal modulatory role was not always evident in all brain areas as revealed by long-day photic cycles producing diminished (p < 0.01) binding levels in the anterior neostriatum and the nucleus rotundus of both castrated and gonadally intact animals, although elevated values were also found in the substantia grisea centralis (p < 0.05) of the same animals. Saturation binding studies revealed that gonadal and/or photic effects induce alterations in the number of binding sites, whereas the affinity constant varied only in some hypothalamic sites. Testing of GABAergic activity on 2-[125I] iodomelatonin binding levels showed that this inhibitory neurotransmitter was responsible for increasing low receptor values. Moreover, GABA-dependent influences were shown to be mediated via a GABAA receptor subtype since bicuculline (specific antagonist of this site) inhibited the elevated GABA-induced melatonin binding levels in the above brain sites of the gonadally intact quail exposed to both photoperiod cycles. Even in this case, melatonin binding changes were due to the variations in the number of binding sites. The apparent GABAergic-gonadal influence resulting in changes of the 2-[125I] iodomelatonin binding values, under the different photic conditions, provides evidences of other probable neural mechanisms that entrain circadian rhythmicity in neuroendocrine activities and in sociosexual behaviors.

Role of the GABA chloride ion channel component on aggressive behavior in the male crab.

Picrotoxin blocking effects on GABA-induced inhibition of lateral merus display in the male crab Carcinus mediterraneus suggest that the chloride ion channel component of the GABA molecule is involved in the control of this defensive behavior. The low GABA doses (3 and 5 micrograms/g body weight) inhibited lateral merus display as early as 10 min after drug treatment while the administration of higher GABA concentrations (greater than 5 micrograms/g) prolonged the duration of the behavioral effects. The administration of 1 microgram/g picrotoxin to the animals treated with the effective GABA doses (5, 10 and 20 micrograms/g) restored lateral merus display. The antagonizing activity of picrotoxin on the inhibitory GABA effects, in a temporal manner, demonstrates that GABAergic sites other than peripheral ones are probably participating with the regulation of this agonistic posture. Quantitative autoradiography results revealed interesting receptor levels changes of the specific chloride ion channel antagonist [35S] t-butylbicyclophosphorothionate in the different brain areas of the male crab displaying lateral merus with respect to normal nonreactive animals. Elevated receptor binding levels were encountered in the middle and posterior brain area whereas low levels were obtained at the anterior level. Both the behavioral and autoradiographic results suggest that the defensive type of aggression behavior in crustacean may not only be mediated by a peripherally controlled GABA-gated chloride ion flux but also by a central GABAergic mechanism.

Technetium-99m sestamibi imaging in the detection of axillary lymph node involvement in patients with breast cancer.

BACKGROUND: The status of the axillary lymph nodes is the most important prognostic factor in breast cancer, and the findings of axillary node dissection remain the gold standard for the patients staging and prognosis. The aim of this study was to evaluate the usefulness of Tc-99m sestamibi scintigraphy in the detection of axillary node involvement. MATERIALS AND METHODS: Forty-nine patients (age range: 32-72 years) with breast cancer were studied. Dynamic images (1-20 minutes post-injection of the radiopharmaceutical) followed by multiple planar views and tomographic images were performed. Final diagnosis was achieved by histology after surgery. RESULTS: Metastatic axillary lymph node involvement was present in 21 patients: sensitivity was 81% (17/21) for tomographic and 61.9% (13/21) for planar images; specificity was 92.9% (26/28) and 96.4% (27/28), respectively. CONCLUSIONS: Tc-99m sestamibi imaging is a promising noninvasive method to detect axillary node metastases in patients with breast cancer, tomography appears more sensitive than planar views.

Scintimammography with technetium-99m tetrofosmin in suspected breast cancer.

BACKGROUND: Scintimammography with Tc-99m sestamibi has recently demonstrated a clinical usefulness in the evaluation of patients with breast lesions. The aim of this study was to assess the potential role of scintimammography using Tc-99m tetrofosmin in the detection of breast cancer. MATERIALS AND METHODS: Fifty-five patients (age range: 33-76 years) with suspicious breast abnormalities detected by mammography, and ten controls were examined. Dynamic images (1-20 min post-injection of the radiopharmaceutical) followed by three planar views were performed. Final diagnosis was achieved by hystology after surgery or excisional biopsy. RESULTS: A total of 59 breast lesions were considered. The sensitivity of Tc-99m tetrofosmin scintimammography for detection of primary breast cancer was 93.1% (27/29) and the specificity was 93.3% (28/30). No focal uptake was observed in both breasts of the control population. CONCLUSIONS: Tc-99m tetrofosmin scintimammography has high diagnostic accuracy in detecting breast cancer and may have a clinical role as complement to conventional mammography.

A three center study on the diagnostic accuracy of 99mTc-MIBI scintimammography.

In order to assess specificity and sensitivity of the prone scintimammography (PSM) in a large series with 99m-Tc MIBI, we performed a three-center study; 420 patients were studied; after mammography all the patients were submitted to PSM and biopsy and/or operation. PSM was considered positive if hot spot within the breast was observed. In palpable masses sensitivity was 0.98 and specificity 0.89, non palpable masses showed a sensitivity of 0.62 and a specificity of 0.91. When the cancers were stratified for T category the sensitivity was 0.28 in T1a 0.26 in the group of T1a carcinomas, 0.56 in T1b 0.95 in T1c and 0.97 T2 tumors. Physical factors such as attenuation. Compton scattering from chest, as well as biological factors have a role in breast tumor imaging. In the tumors smaller than 1 cm biological factors are probably involved too.

Single photon emission computerized tomography increases the sensitivity of indium-111-pentetreotide scintigraphy in detecting abdominal carcinoids.

Somatostatin (sms) receptors have been identified in carcinoids (c), so enabling their visualization with 111In-pentetreotide scintigraphy. The aim of this study was to evaluate if single photon emission computerized tomography (SPECT) can increase the sensitivity of sms receptor scintigraphy in the detection of abdominal c. 26 patients (pts) with a present, or previously operated, abdominal carcinoid were submitted to SPECT over the abdomen and multiple planar views after the injection of 111In-pentetreotide. Magnetic resonance imaging and computed tomography were also performed. In 19 pts abnormal sites of uptake were found by SPECT which localized 13 abdominal extrahepatic (in 11 pts) and 45 hepatic lesions (in 15 pts). No pathologic accumulation was seen in 7 pts in complete remission after surgery. Planar images visualized 7 abdominal extrahepatic (in 6 pts) and 26 liver tumor sites (in 10 pts), conventional procedures detected 5 abdominal extrahepatic (in 4 pts) and 36 hepatic lesions (in 10 pts). 111In-pentetreotide SPECT is more sensitive than planar scanning and conventional methods to detect abdominal c, and so may play a major role in the early and accurate mapping of tumour spread.

111In-pentetreotide detection of gastrinoma before and after surgery.

Eighteen patients with Zollinger-Ellison syndrome were studied with 111In-pentetreotide SPECT in order to localize gastrinoma, the tumour responsible for this pathology. NMR imaging was also carried out. Eight patients were operated. 111In-pentetreotide was reinjected 4 hours before operation and the radioactivity of the excised tumours counted. The nature of the withdrawn tissues was assessed by immunohistochemistry (chromogranina A). The scintigraphy was repeated 3-6 months after surgery. 111In pentetreotide SPECT was more sensitive than NMR. It was also absolutely specific because all the radioactive tumours excised showed positive chromogranin A staining. The radioactivity/gram counted in gastrinomas exceeded 10 fold the hepatic and biliary radioactivity and 20-100 folds the radioactivity of blood and omentum. In all the operated patients but three, the scintigraphy performed after surgery did not detect tumours. However complete eradication did not occur, because though 3-6 months after surgery the gastrinemia was significantly lower with respect to pre-surgery results it did not return to normal values in all patients but two.

Effects of N omega-nitro-L-arginine methyl ester on benzodiazepine binding in some limbic areas of hyperlipidaemic rats.

Quantitative autoradiography techniques were used to evaluate the chronic effects of the potent nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester, on the binding pattern of [3H]flunitrazepam (benzodiazepine agonist) in some behaviorally key limbic areas of the genetic hyperlipidaemic Pittsburg Yoshida rat. Administration of this potent synthase inhibitor was capable of supplying higher and moderately higher binding levels in the basolateral amygdala nucleus (+52%) and in the oriens-pyramidalis CA1 hippocampus layer (+38%), respectively. When we tested for the binding changes in the presence of GABA (principal benzodiazepine modulator) we noticed that a physiological concentration (20 microM) of this inhibitory neurotransmitter was sufficient to induce notable changes in other limbic areas. In fact, lower binding values (-65%) were reported for the bed nucleus of stria terminalis whereas moderately higher values (+38%) were obtained for the radiatum-lacunosum molecular CA1 hippocampus layer. From the saturation studies, it was possible to observe that the major receptor variations provoked by the potent synthase inhibitor were not only due to changes in the total number of binding sites because there were variations, as in the case of the basolateral amygdala nucleus, that were instead due to differences in the affinity binding state. These results provide evidences of a GABAergic-nitric oxide synthase inhibitor interaction that might also be involved in the regulation of convulsive, anxiolytic, and aggressive behaviors that are modulated at the benzodiazepine site.

99Tcm-sestamibi scintimammography in patients with suspicious breast lesions: comparison of SPET and planar images in the detection of primary tumours and axillary lymph node involvement.

Planar scintimammography with 99Tcm-sestamibi (99Tcm-MIBI) has been shown to be useful in diagnosing breast carcinoma. The aim of this study was to compare single photon emission tomography (SPET) and planar imaging for scintimammography with 99Tcm-MIBI in the detection of primary breast cancer and axillary lymph node involvement. Sixty-three females with mammographically suspicious lesions and 12 controls were evaluated. Dynamic images were acquired commencing immediately after the injection of the radiopharmaceutical, followed by multiple planar images in the supine and prone positions plus SPET supine imaging. A final histopathological diagnosis was achieved after surgery. A total of 66 breast lesions were considered. No focal uptake of 99Tcm-MIBI was observed in the breasts or axillas of the controls. In the patients with breast cancer, the sensitivity was 92.9% (39/42) for SPET, 71.4% (30/42) for supine and 85.7% (36/42) for prone planar imaging, respectively; the specificity was 87.5% for SPET and 91.6% for the planar scans. Metastatic axillary lymph node involvement was seen in 19 patients: the sensitivity was 84.2% (16/19) for SPET and 63.2% (12/19) for planar images; the specificity was 91.3% and 95.7% respectively. Our results confirm the high diagnostic accuracy of 99Tcm scintimammography in the diagnosis of breast cancer, and suggest that SPET is more sensitive than planar images, especially in detecting axillary lymph node involvement.

Brain natriuretic peptide (BNP)-like immunoreactivity in the central nervous system of the crested newt.

The distribution of brain natriuretic peptide (BNP)-like immunoreactivity (ir) was studied in the brain of a urodele amphibian, the crested newt Triturus carnifex Laur. BNP-like immunoreactive neurons were found mainly in the caudal hypothalamus (retro- and supra-chiasmatic areas) and in the preoptic area. A widespread innervation throughout the brainstem as far as the spinal cord was also observed. By double immunostaining (after section incubation with a-BNP and a-tyrosine hydroxylase-TH-antibodies), close topographical relationships between BNP-like and TH-like immunoreactive neurons within the hypothalamus were found.

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.

Immunoscintigraphy of venous thrombi: clinical effectiveness of a new antifibrin D-dimer monoclonal antibody.

Safety and thrombus imaging capabilities of the 99mTc-labeled form of a new F(ab')2 monoclonal antibody (MoAb) against fragment D dimers from cross-linked human fibrin, previously shown to be effective labeled to 131I in detecting venous thrombi in the rabbit, were investigated. Sixteen patients (seven men, mean age: 60+/-7 years) with deep (n = three) and superficial (n = 13) venous thromboses of the lower limbs documented at echo-Doppler study underwent, 24 hours before saphenous vein stripping, a scintigraphic study after IV injection of the 99mTc-MoAb (1,129+/-275 MBq/mL), acquiring dynamic images, as well as early and delayed static images of lower limbs. Tracer activity was compared in normal and pathologic areas. At the operation, vessel wall including the thrombotic lesion was isolated, weighed, and counted. Blood radioactivity and MoAb concentration were also measured. No adverse reaction was observed after MoAb administration. Thrombus site appeared as a focal area (hot spot) of asymmetrically increased tracer uptake, already detectable at early images in all patients. All thrombi detected at echo-Doppler study (n=25) were confirmed at scintigraphic study, which showed four additional hot spots subsequently confirmed to represent thrombi at operation. Average percent ratio between pathologic and normal regions was 1.51+/-1.34 (p < 0.05) at time-activity curves, 2.27+/-1.1 (p < 0.05) at early static images, and 2.15+/-1.2 (p < 0.05) at delayed images, respectively. Thrombus-to-blood uptake ratio was 4.3+/-0.9 (p < 0.01). The F(ab')2 MoAb proved to be safe, and low levels of antimouse antibodies were detected in response, although further studies are needed to assess tolerance and effectiveness in case of a second administration in the same patient. The 99mTc-labeled MoAb was very effective in identifying venous thromboses both at deep and superficial localizations, although its sensitivity and specificity need be evaluated in a more numerous group, including also patients with different and clinically more relevant localizations, such as caval thromboses. However, the possibility of obtaining high-quality images within 4 hours of MoAb administration is clinically relevant, and carries also therapeutic implications, especially in pulmonary thromboembolism.

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.