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In vivo technetium-99m S12 antibody imaging of platelet alpha-granules in rabbit endothelial neointimal proliferation after angioplasty.

To examine the specificity of technetium-99m monoclonal antibody (S12) imaging for identifying activated platelets at interventional injury sites in atherosclerotic rabbit arteries, subgroups of unheparinized rabbits (n = 39) underwent serial percutaneous transluminal aortic angioplasty (PTA) procedures (with or without intravascular stent placement) followed by in vivo and then ex vivo gamma camera imaging, scanning, and immunoelectron microscopy to determine the intravascular loci of S12 Fab' antibody binding. Despite angiographic vessel patency, image-derived ratios of in vivo S12 binding in injured versus uninjured vascular segments were significantly increased (p less than 0.05) after one PTA (1.3 +/- 0.17, n = 7), PTA twice at 6-week intervals (1.4 +/- 0.22, n = 7), and PTA plus stent placement (1.6 +/- 0.28, n = 7) compared with control experiments (1.1 +/- 0.13, n = 7). Ex vivo imaging of blood-free excised aortas confirmed S12 localization at PTA (2 +/- 0.4, n = 3) and PTA plus stent placement (5 +/- 3.8, n = 7) sites (both p less than 0.05 versus controls). S12 antibody uptake decreased significantly (p less than 0.05) at 1 week after PTA plus stent placement in vivo (1.1 +/- 0.10, n = 4) and ex vivo (1.6 +/- 0.7, n = 3). Electron microscopic studies confirmed dense platelet, fibrin, and red blood cell deposition in regions of acute injury, with endothelial neointimal proliferation at 1 week after PTA. Immunoelectron microscopic studies confirmed specific in vivo S12 binding (22:1 versus nonrelevant IgG) at sites of alpha-granule GMP-140 expression in activated platelets. Therefore, S12 studies may be useful to localize sites of platelet-derived mitogen release at arterial PTA injury sites.

Angioplasty, Balloon↗

Noninvasive identification of myocardium at risk in patients with acute myocardial infarction and nondiagnostic electrocardiograms with technetium-99m-Sestamibi.

BACKGROUND: Patients who have chest pain without electrocardiographic ST elevation are not candidates for thrombolytic therapy in most clinical trials. This study examined the value of technetium-99m-Sestamibi tomographic imaging to assess myocardial perfusion in patients during chest pain without ST elevation. METHODS AND RESULTS: Tc-99m-Sestamibi was injected in 14 patients who had chest pain without ST elevation, who subsequently developed enzymatic evidence of myocardial infarction within 24 hours. Tomographic imaging was performed 1-6 hours after injection. Thirteen of 14 patients showed significant perfusion defects indicative of acute myocardial infarction consistent with absent perfusion (20 +/- 15% of the left ventricle; range, 2-53%); one patient had normal images. Because of the absence of definitive electrocardiographic changes, only five patients received reperfusion therapy within 6 hours of the onset of chest pain. Regional wall motion abnormalities were present in nine of nine patients undergoing contrast ventriculography and correlated with the location of the Tc-99m-Sestamibi perfusion defect. At the time of subsequent coronary angiography, total arterial occlusion was present in 11 of the 14 patients. The infarct-related artery could be identified in 13 of the 14 patients. In six of these 13 patients, the left circumflex was the infarct-related artery. CONCLUSIONS: Patients who have chest pain without electrocardiographic ST elevation may have arterial occlusion and significant myocardium at risk. Tc-99m-Sestamibi imaging may be of benefit in identifying these patients early so that they can be considered for acute reperfusion therapy.

Aged↗

Imaging multidrug resistance P-glycoprotein transport function using microPET with technetium-94m-sestamibi.

The best characterized mechanism of multidrug resistance (MDR) in cancer involves the MDR1 efflux transporter P-glycoprotein (Pgp). The positron-emitting radiotracer hexakis(2-methoxyisobutylisonitrile)-(94m)Tc ((94m)Tc-MIBI) was synthesized and validated in cell transport studies as a substrate for MDR1 Pgp. In vivo small-scale PET imaging and biodistribution studies of mdr1a/1b (-/-) gene deleted and wild-type mice demonstrated the use of (94m)Tc-MIBI to detect Pgp function. The reversal effect of a Pgp modulator was shown in tissue distribution studies of KB 3-1 (Pgp-) and KB 8-5 (Pgp+) tumor-bearing nude mice. The current (94m)Tc-MIBI experiments parallel previous studies employing (99m)Tc-MIBI, showing essentially identical performance of the two technetium radiotracers and providing biological validation of (94m)Tc-MIBI for PET imaging of multidrug resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Effect of pattern of aerosol inhalation on clearance of technetium-99m-labeled diethylenetriamine pentaacetic acid from the lungs of normal humans.

The clearance rate of inhaled aerosols of technetium-99m-labeled diethylenetriamine pentaacetic acid (99mTc-DTPA) from the lungs provides a rapid, clinically useful, noninvasive index of pulmonary epithelial permeability. In order to identify a method that minimizes intrasubject and intersubject variability and thereby provides a reliable means to identify patients with abnormal values, we administered a submicronic aerosol of 99mTc-DTPA to 10 healthy, nonsmoking male subjects with either tidal breathing (Vtidal) or multiple vital capacity maneuvers (VVC). Subjects then spontaneously breathed room air while counting continued for 30 min. Monoexponential clearance rates over 7, 15, and 30 min were compared with a two-compartment, biexponential analysis over 30 min. Intrasubject reproducibility was evaluated by repeating clearance 2 to 156 days later. Monoexponential clearance following VVC at 30 min equaled 1.36 +/- 0.55%/min compared with 0.83 +/- 0.25%/min for Vtidal (p less than 0.025). VVC inhalations resulted in a larger fast compartment of 16 +/- 12% compared with 3 +/- 2% with tidal breathing (p less than 0.01). The least intrasubject variability with coefficient of variation (CV) of +/- 18% was obtained with monoexponential analyses after Vtidal during 15 min of scanning and with either breathing maneuver over 30 min. Monoexponential clearance for 30 min with Vtidal gave the least scatter between subjects, with CV of +/- 30%. These data show that simple tidal inhalations of 99mTc-DTPA followed by a monoexponential analysis of the 30-min time-activity curve from both lungs minimize the degree of variability between and among subjects and provide a predicted normal value of clearance of 0.83 +/- 0.25%/min. The development of a more rapid curvilinear clearance followed by delivery VVC suggests that several deep breaths transiently increase epithelial permeability or reduce the volume of liquid in the alveolar subphase in some regions. Resting for 20 min prior to inhaling the aerosol of 99mTc-DTPA is recommended to avoid alterations in clearance rates from deep breathing.

Administration, Inhalation↗

Pathophysiology of technetium-99m stannous pyrophosphate and thallium-201 scintigraphy of acute anterior myocardial infarcts in dogs.

In 17 dogs with acute myocardial infarcts produced by ligation of the proximal left anterior descending coronary artery, a comparative study was made of myocardial scintigrams obtained with technetium-99m stannous pyrophosphate (99mTc-PYP) and thallium-201 (201T1), tissue levels of 99mTc-PYP and 201T1 uptake, histopathologic alterations, and regional myocardial perfusion measured with radioactive microspheres. 9 of the 10 hearts examined histologically had transmural infarcts with outer peripheral, inner peripheral, and central zones characterized by distinctive histopathologic features. A progressive reduction in myocardial blood flow was demonstrated between normal myocardium and the centers of the infarcts, and correlated well with progressive reduction in 201T1 upatke in the same regions. Marked 99mTc-PYP concentration occurred in areas with partial to homogeneous myocardial necrosis and residual perfusion located in the outer peripheral regions of the infarcts. The latter areas also were characterized by the presence of muscle cell calcification. The patterns of distribution of 99mTc-PYP and 201T1 explained the filling defects on 201T1 myocardial scintigrams and the doughnut patterns on 99mTc-PYP myocardial scintigrams in dogs with transmural infarcts. One dog with a subendocardial infarct had a small homogeneous area of activity on the 99mTc-PYP myocardial scintigram, and showed marked uptake of 99mTc-PYP in subendocardial areas of extensive necrosis and calcification still receiving some coronary perfusion. Thus, the data indicate that the status of regional myocardial perfusion is a key determinant for the occurrence of distinctive patterns of myocardial necrosis and for the scintigraphic detection of acute myocardial infarcts with 99mTc-PYP and 201T1.

Acute Disease↗

Sites and mechanisms of localization of technetium-99m phosphorus radiopharmaceuticals in acute myocardial infarcts and other tissues.

This study was performed to elucidate the localization at the cellular level of technetium-99m phosphorus ((99m)Tc-P) radiopharmaceuticals in acute myocardial infarcts and the mechanisms responsible for (99m)Tc-P uptake in acute myocardial infarcts and other tissues. In 20 dogs with proximal left anterior descending coronary arterial ligation for 1-3 days, elevated calcium levels were measured at all sites of increased (99m)Tc-P uptake (acute myocardial infarcts, necrotic thoracotomy muscle, lactating breast, and normal bone); however, a consistent linear relationship between (99m)Tc-P and calcium levels was not observed. A strong correlation (r = 0.95 and 0.99, n = 2 dogs) was demonstrated between levels of (3)H-diphosphonate and (99m)Tc-P in infarcted myocardium. Autoradiographic studies with (3)H-diphosphonate revealed extensive labeling in the infarct periphery which contained necrotic muscle cells with features of severe calcium overloading, including widespread hypercontraction as well as more selective formation of mitochondrial calcific deposits. Autoradiography also demonstrated labeling of a small population of damaged border zone muscle cells which exhibited prominent accumulation of lipid droplets and focal, early mitochondrial calcification. Cell fractionation studies revealed major localization of both (99m)Tc-P and calcium in the soluble supernate and membrane-debris fractions of infarcted myocardium and less than 2% of total (99m)Tc-P and calcium in the mitochondrial fractions; however, electron microscopic examination showed that mitochondria with calcific deposits were not preserved in the mitochondrial fractions. In vitro studies evaluating the role of serum protein binding on tissue uptake of (99m)Tc-P agents demonstrated that, in spite of significant complexing with serum proteins, serum (99m)Tc-P activity retained the ability to adsorp to calcium hydroxyapatite and amorphous calcium phosphate. In vivo studies showed that concentration of human serum albumin (labeled with iodine-131) in infarcted myocardium reached a maximum of only 3.8 times normal after a circulation time of 96 h, whereas (99m)Tc-P uptake was at least 10 times normal after a circulation time as short as 1 h. It is concluded that: (a) (99m)Tc-P uptake in acutely infarcted myocardium, and possibly other types of soft tissue damage, is limited to necrotic and severely injured cells; (b) concentration of (99m)Tc-P results from selective adsorption of (99m)Tc-P with various forms of tissue calcium stores, including amorphous calcium phosphate, crystalline hydroxyapatite, and calcium complexed with myofibrils and other macromolecules, possibly supplemented by calcium-independent complexing with organic macromolecules; and (c) lack of a linear relationship between (99m)Tc-P and tissue calcium levels mainly results from local differences in composition and physicochemical properties of tissue calcium stores and from local variations in levels of blood flow for delivery of (99m)Tc-P agents.

Animals↗

Lupus carditis: evaluation with technetium-99m MIBI myocardial SPECT and heart rate variability.

The objective of this paper was to investigate the incidence of myocardial perfusion defects in patients with systemic lupus erythematosus (SLE) associated with dysautonomic alterations. Twenty patients without any sign or symptoms of heart disease, selected from a larger population of patients with SLE, underwent technetium-99m sestamibi (Tc-99m MIBI) single photon emission computed tomography (SPECT), at rest and after dipyridamole infusion; they also underwent heart rate variability (HRV) examination by a 24 hour ambulatory electrocardiography, analyzing in the time domain the standard deviation of the R-R intervals average (SDNN) and the percentage of R-R adjacent intervals differing from each other more than 50 msec (pNN50); in the frequency domain the low (LF) and high frequencies (HF) were analyzed. Twenty healthy volunteers served as control group for heart rate variability. At MIBI-SPECT examination, the scan was found abnormal in 15 patients and normal in five: three patients demonstrated reversible defects in the anteroseptal region, four had irreversible defects in a region (two in the anteroseptal region and two in the lateral region), two had rest defects in two different regions (lateral and inferior, lateral and anteroseptal) that improved during dipyridamole scan, and six had both reversible and irreversible defects: four in a single segment (three anteroseptal and one lateral, and two in two different regions, particularly anteroseptal and lateral, lateral and inferior). All 20 patients showed significantly lower HRV parameters in comparison with the control group, except for pNN50, which indicates decreased physiologic periodic fluctuations of the autonomic nervous system. In six patients who underwent coronary angiography, the epicardial vessels were found completely normal. In view of the high incidence of myocardial hypoperfusion in patients with HRV alterations, the authors hypothesize that autonomic dysfunction may be associated with microvascular disease or metabolic alteration. They also believe that MIBI scintigraphy is a suitable technique in detecting myocardial damage in SLE patients free of clinical manifestation.

Adolescent↗

Evaluation of nasal mucociliary clearance function in allergic rhinitis patients with technetium 99m-labeled macroaggregated albumin rhinoscintigraphy.

Nasal mucociliary clearance is the first line of defense of the ciliated epithelium of the respiratory tract against inhaled particles. Several rhinopathic conditions involve alterations in nasal mucociliary clearance. The purpose of this study was to assess the clinical role of rhinoscintigraphy in evaluation of nasal mucociliary clearance function in allergic rhinitis patients and in sinusitis patients and healthy controls for comparison. A technetium 99m-labeled macroaggregated albumin (Tc-99m MAA) drop was deposited on the floor of the nasal meatus about 1 cm behind the mucocutaneous junction, and its course was followed with a gamma camera. The nasal mucociliary clearance function was measured as the velocity of the nasal mucociliary transport of the Tc-99m MAA droplet. The mean velocity of nasal mucociliary transport in the allergic rhinitis patients was 2.71 +/- 0.76 mm/min (2.65 +/- 0.76 mm/min in the right nostril; 2.77 +/- 0.76 mm/min in the left nostril). The mean velocity of nasal mucociliary transport in the sinusitis patients was 1.80 +/- 0.64 mm/min (1.79 +/- 0.65 mm/min in the right nostril; 1.82 +/- 0.63 mm/min in the left nostril). The mean velocity of nasal mucociliary transport in the 25 healthy controls was 4.28 +/- 1.38 mm/min (4.30 +/- 1.35 mm/min in the right nostril; 4.27 +/- 1.42 mm/min in the left nostril). A significant difference in nasal mucociliary clearance was observed among the 3 groups. We suggest that Tc-99m MAA rhinoscintigraphy may be a useful noninvasive tool to evaluate the nasal mucociliary clearance function in allergic rhinitis patients.

Adult↗

Detection of recurrent nasopharyngeal carcinomas with technetium-99m methoxyisobutylisonitrile single photon emission computed tomography in patients with indeterminate magnetic resonance imaging findings after radiotherapy.

The aim of this study was to evaluate the effectiveness of technetium-99m methoxyisobutylisonitrile (Tc-99m MIBI) single photon emission computed tomography (SPECT) for detecting recurrent nasopharyngeal carcinomas (NPCs) when magnetic resonance imaging (MRI) findings are indeterminate. Twenty-eight NPC patients who had received radiotherapy and had indeterminate MRI findings were included in the study. We performed MRI, Tc-99m MIBI SPECT, and biopsy at least 4 months after radiotherapy and within 1 week. The final results were based on histopathologic findings and clinical follow-up after 6 or more months. For detecting recurrent NPC in indeterminate MRI findings, the sensitivity, specificity, and accuracy of Tc-99m MIBI SPECT were 85.7%, 92.9%, and 89.3%, respectively. Our findings suggest that Tc-99m MIBI SPECT may be an effective tool for detecting recurrent NPC when MRI findings are indeterminate.

Adult↗

Preliminary study on immunoscintigraphy of a murine lymphoma using technetium-99M labeled chicken antibody.

AIMS AND BACKGROUND: Radiolabeled antibodies generated against tumor-associated antigens are used for immunoscintigraphy to detect tumors and tumor metastases. Although successful tumor imaging has been achieved using trace-labeled murine monoclonal antibodies, such antibodies often lead to the development of human anti-murine antibodies (HAMA), which limit their subsequent administration for tumor imaging and therapy. It has been reported recently that chicken polyclonal antibodies have high affinity and specificity for the antigen against which they are raised and do not have any immunological cross-reactivity with HAMA. METHODS: The present study deals with immunoscintigraphy of Dalton's lymphoma, an experimental tumor model using chicken antibodies generated against Dalton's lymphoma-associated antigen (DLAA) and labeled with technetium-99m ((99m)Tc). RESULTS: Scintigrams showed specific uptake of the radiolabel resulting in clear tumor images. The radioactivity uptake of the chicken anti-DLAA antibody was about twofold higher than that of the non-specific chicken antibody. CONCLUSIONS: The results demonstrate the potential of chicken antibody for in vivo radioimmunodetection and localization of tumors.

Animals↗

Technetium 99mTc-HMPAO SPECT in children and adolescents with neurologic disorders.

We evaluated regional cerebral blood flow with technetium 99mTc hexamethylpropyleneamineoxime single photon emission computed tomography (SPECT) in 20 children and adolescents with neurologic dysfunction of varied etiology and abnormal electroencephalograms (EEGs). All patients were also examined with computed tomography (CT) and magnetic resonance imaging (MRI). Abnormal perfusion was found in 17 (85%) of 20 SPECT scans. Abnormal CT or MRI scans were noted in nine (45%) and in 10 (50%) of 20 cases, respectively. In eight (73%) of 11 cases with normal CT scans and in seven (70%) of 10 with normal MRI scans, the SPECT scan was abnormal. Abnormal regional cerebral blood flow on SPECT scans correlated better with EEG abnormalities than with neurologic examination or CT or MRI scan findings. We conclude that in children and adolescents with a spectrum of neurologic diseases and abnormal EEGs, abnormalities of brain structure or function are more likely to be documented by SPECT than by CT or MRI scans. SPECT findings correlate well with the location and type of EEG abnormality.

Adolescent↗

Distribution of technetium-99m-labelled QVAR delivered using an Autohaler device in children.

QVAR, an extrafine hydrofluoroalkane/beclomethasone dipropionate formulation, has been shown to double lung deposition in adults. The aim of the present study was to assess the total body deposition and distribution of technetium-99m-labelled (99mTc) QVAR in children after inhalation via an Autohaler. Sixteen male asthmatic children (5-14 yrs) inhaled labelled drug (<4 MBq 99mTc; 100 microg beclomethasone dipropionate) via an Autohaler within 30 min after salbutamol (200 microg) administration. Simultaneous anterior and posterior planar scintigraphic scans (120 s acquisition time) were collected after inhalation of labelled drug. Mean+/-SD lung deposition of labelled drug (attenuation-corrected; percentage of ex-actuator dose) was 36.9+/-9.2, 46.5+/-11.6 and 54.1+/-10.7% in children aged 5-7, 8-10 and 11-14 yrs, respectively. Combined oropharyngeal and gastrointestinal deposition was 59.7+/-8.2, 48.9+/-12.3 and 40.3+/-11.8%. Lung deposition positively correlated with the forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). Gastrointestinal dose negatively correlated with the FEV1, FVC, height and age. In older children (11-14 yrs), lung deposition was almost identical to that reported in adults using QVAR. In children aged 5-10 yrs, lung deposition using QVAR was greater than the levels measured using other commercial aerosol delivery systems. Oropharygeal and gastrointestinal deposition was inversely related to age.

Administration, Inhalation↗

Clearance of technetium-99m-DTPA and HRCT findings in the evaluation of patients with Idiopathic Pulmonary Fibrosis.

BACKGROUND: Clearance of inhaled technetium-labeled diethylenetriamine pentaacetate (99mTc-DTPA) is a marker of epithelial damage and an index of lung epithelial permeability. The aim of this study was to investigate the role of 99mTc-DTPA scan in patients with Idiopathic Pulmonary Fibrosis (IPF). Our hypothesis is that the rate of pulmonary 99mTc-DTPA clearance could be associated with extent of High Resolution Computed Tomography (HRCT) abnormalities, cell differential of bronchoalveolar lavage fluid (BALF) and pulmonary function tests (PFTs) in patients with IPF. METHODS: We studied prospectively 18 patients (14 male, 4 female) of median age 67 yr (range 55-81) with histologically proven IPF. HRCT scoring included the mean values of extent of disease. Mean values of these percentages represented the Total Interstitial Disease Score (TID). DTPA clearance was analyzed according to a dynamic study using a Venticis II radioaerosol delivery system. RESULTS: The mean (SD) TID score was 36 +/- 12%, 3 patients had mild, 11 moderate and 4 severe TID. Abnormal DTPA clearance half-time (t1/2 < 40 min) was found in 17/18 (94.5%) [mean (SD) 29.1 +/- 8.6 min]. TID was weakly correlated with the DTPA clearance (r = -0.47, p = 0.048) and with % eosinophils (r = 0.475, p = 0.05). No correlation was found between TID score or DTPA and PFTs in IPF patients. CONCLUSION: Our data suggest that 99mTc-DTPA lung scan is not well associated with HRCT abnormalities, PFTs, and BALF cellularity in patients with IPF. Further studies in large scale of patients are needed to define the role of this technique in pulmonary fibrosis.

Aged↗

Single photon emission computerised tomography in elderly patients with Alzheimer's disease and multi-infarct dementia. Regional uptake of technetium-labelled HMPAO related to clinical measurements.

Single photon emission computerised tomography (SPECT) was used to measure regional brain uptake of technetium-99m hexamethylpropyleneamine oxine (Tc99m-HMPAO) in elderly patients with Alzheimer's disease (AD), multi-infarct dementia (MID) and normals (n = 20 in each group). Different patterns of uptake were found between groups when cortical uptake was normalised to cerebellar uptake. Reductions occurred in all regions in AD, being most marked in temporal and posterior parietal areas. Significant correlations were found in AD between memory impairment and decreased temporal uptake bilaterally, and between duration of illness and reduced uptake in most brain regions. MID patients showed higher uptake in the anterior parietal region than did the other groups. A variable comparing anterior to posterior uptake significantly discriminated the two patient groups.

Aged↗

Pulmonary uptake of technetium 99m macroaggregated albumin: a predictor of gastrointestinal toxicity during hepatic artery perfusion.

Hepatic artery infusion of 5-fluoro-2-deoxyuridine (5-FUdR) provides high hepatic drug levels but little systemic toxicity, since, by this route of administration, the drug is detoxified by the hepatocytes. Slow infusion of technetium 99m- (99mTc) labeled macroaggregated albumin (MAA) through the hepatic artery is an aid in catheter placement, in predicting response of liver metastases to therapy, and in identifying extra-hepatic flow in the gastroduodenal or splenic arteries as an indicator of systemic toxicity. Marked pulmonary uptake of this tracer after slow radionuclide hepatic angiography was noted in four patients who showed major gastrointestinal (GI) toxicity. A retrospective examination of pulmonary accumulation of 99mTcMAA as a predictor of GI toxicity is the subject of this paper. Two groups of patients were evaluated. The first group consisted of 14 consecutive patients in whom continuous infusion of drug was administered by an external pump by way of a percutaneous catheter. Patients received baseline and follow-up (seven to 27 days) slow-infusion tracer studies (2 to 4 mCi 99mTcMAA at 10 to 21 mL/h). The second group included 14 consecutive patients who were receiving intraarterial chemotherapy by a totally implantable pump system. All received baseline slow-infusion studies (2 to 4 mCi 99mTcMAA at approximately 0.5 to 1.0 mL/min). The percentage of the injected dose in the lung was determined. Patients with greater than 20% of tracer in the lung after radionuclide hepatic angiography had significantly greater severe GI toxicity than patients with baseline values of less than 20%. Our findings support the existence of hepatic arteriovenous (A-V) communications in some patients and suggest that they are present pretherapy. Presence of these A-V communications, which can result in a vascular bypass of normal hepatic parenchyma and the subsequent decrease in hepatic detoxification of chemotherapeutic agents, is the likely cause of GI toxicity. Pulmonary uptake of tracer injected in the hepatic artery may be useful in quantifying the degree of shunting and facilitate the monitoring of potential systemic toxicity.

Antineoplastic Agents↗

Role of technetium 99m-labeled monoclonal antibody in the management of melanoma patients.

PURPOSE: A study was performed to assess the usefulness of a radiolabeled monoclonal antibody (MoAb; technetium 99m NR-ML-05 Fab) as a detecting agent, as well as to evaluate its role in the overall decision-making process in the management of cutaneous malignant melanoma. PATIENTS AND METHODS: Twelve patients with histologically confirmed primary cutaneous melanoma and palpable regional nodes were injected with MoAb NR-ML-05 Fab, radiolabeled with 20 to 30 mCi of 99mTc. Whole-body anterior and posterior images were obtained. Left and right lateral views of the head and anterior and posterior views of the chest, abdomen, pelvis, and extremities were obtained, as were selected single-photon emission computed tomographic (SPECT) views of regional lymph nodes and areas of known or suspected lesions. RESULTS: In nine of 12 patients, clinical and/or MoAb evolution identified 30 discrete sites of suspected melanoma. The remaining three patients showed no positive sites, and there was no evidence of metastatic melanoma. All 30 sites were examined microscopically, and melanoma was confirmed histologically in 23. The remaining seven were negative. MoAb imaging detected 21 (true-positive) but failed to detect two (false-negative) lesions. Sensitivity was 91% (21 of 23); positive predictive value was 95% (21 to 22). CONCLUSIONS: MoAb imaging seems to provide an excellent way to obtain information with regard to the metastatic status of melanoma patients. Immunocytochemistry showed that MoAb (NR-ML-05) is as sensitive as the S-100 antibody and probably more sensitive than the commercially available antimelanoma antibody HMB-45.

Adult↗

Technetium 99m-labeled IMMU-4, a monoclonal antibody against carcinoembryonic antigen, for imaging of occult recurrent colorectal cancer in patients with rising serum carcinoembryonic antigen levels.

PURPOSE: We tested whether nuclear imaging with technetium 99m-labeled murine monoclonal antibody (MoAb) against carcinoembryonic antigen (CEA) IMMU-4 will detect recurrent colorectal disease in patients with a rising serum CEA level but negative abdominal and pelvic computed tomographic (CT) scan, chest radiograph, and colonoscopy, or barium enema. PATIENTS AND METHODS: Sixteen patients with completely resected, CEA-producing colorectal cancer were given 1 mg of 99mTc-labeled IMMU-4 intravenously with no toxic side effects. Planar and single-photon emission CT (SPECT) scans were acquired at 6 hours. Fifteen patients underwent an exploratory laparotomy at 24 hours. Results of the scintigraphy were correlated with surgical findings. RESULTS: Twelve of 15 patients (80%) had true-positive (TP) scans when correlated with surgery. Two of 15 (13%) had true-negative (TN) scans inasmuch as exploratory laparotomy failed to detect recurrent disease. A false-positive (FP) scan was obtained in one of 15 (7%). There were no false-negative (FN) scans. Sensitivity, specificity, accuracy, and the positive predictive value (PPV) were 100%, 67%, 93%, and 92%, respectively. Twenty-six histologically confirmed areas of malignancy were found and correlated with areas of increased activity seen on IMMU-4 scintigraphy. Twenty-one were TP; five were not detected by scintigraphy and were thus considered to be FN. There were five FP lesions and 25 TN regions. Sensitivity, specificity, accuracy, and the PPV in these 26 cancer tissues were 81%, 83%, 82%, and 81%, respectively. The median radioactivity ratio of tumorous tissue to normal tissue was 3.33, with a range of 0.89 to 17.16. CONCLUSIONS: These results suggest that 99mTc IMMU-4 scintigraphy is an important addition to the armamentarium available for diagnostic imaging and may help detect occult metastatic cancer missed by abdominal and pelvic CT in patients with rising CEA levels.

Adult↗