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Biomedical subjects

D Front

Publications and source records attributed to D Front.

At least 73 records · Page 4Linked to original sources

Labeling of sarcoma associated monoclonal antibody with 111In, 67Ga and 125I.

Labeling of human sarcoma-associated murine monoclonal antibody (MAb) 23H7 with 67Ga and 111In by the bifunctional ligand method is reported. 67Ga was chelated to the MAb via desferrioxamine B and 111In via the cyclic anhydride of DTPA. Higher specific activity was obtained with 67Ga (4-5 microCi/micrograms) as compared with 111In (2 microCi/micrograms). The binding capacity of the MAb was confirmed by repeated indirect immuno-fluorescence assays performed before and after labeling. A fast blood clearance was observed: 33% recovered dose (R.D.) blood level 3 h post-injection as compared with 56% after injection of control polyclonal IgG. Preliminary results on chemically induced sarcoma bearing mice showed a relatively high tumor uptake of the labeled antibody.

Animals↗

Radionuclide angiography of azygos continuation of inferior vena cava in left atrial isomerism (polysplenia syndrome).

Interruption of the inferior vena cava with azygos continuation is present in at least 65% of the patients suffering from left atrial isomerism (polysplenia syndrome). First-pass radionuclide angiography using a peripheral vein of the foot correctly diagnosed interruption of the inferior vena cava in seven patients. Four had azygos continuation to the right superior vena cava and in three it was to the left superior vena cava. In all the patients, cardiac catheterization confirmed the diagnosis. Four underwent surgical correction (or palliation), three are waiting for an operation. Radionuclide angiography is a simple outpatient procedure and useful in the clinical diagnosis of this syndrome.

Abnormalities, Multiple↗

Osteomyelitis and soft-tissue infection: differential diagnosis with 24 hour/4 hour ratio of Tc-99m MDP uptake.

The lesion-to-nonlesion 24 hour/4 hour ratio of technetium-99m methylene diphosphonate (MDP) uptake was used to distinguish osteomyelitis from increased bone uptake caused by adjacent soft-tissue infection. In a prospective study, this ratio was measured in 38 patients with 41 sites of increased uptake that were suspected to be osteomyelitis. The mean ratio was 1.18 +/- 0.18 in patients with proved osteomyelitis, which was significantly higher (P less than .001) than that in patients with increased uptake resulting from soft-tissue infection (0.98 +/- 0.05). On the basis of a receiver operating characteristic curve, a ratio of 1.06 was selected as the cutoff for differentiating osteomyelitis from soft-tissue infection. This method resulted in a sensitivity of 82%, a specificity of 92%, and an accuracy of 85%, and it appears to be more reliable than three- and four-phase scintigraphy, which are subjective and nonquantitative techniques.

Adolescent↗

In vivo quantitation using SPECT of radiopharmaceutical uptake by human meningiomas.

A single photon emission computed tomographic method was designed for the measurement of radiopharmaceutical uptake in brain tumors. Results of phantom studies showed a correlation coefficient of .99 when measured volume was compared with actual volume. The correlation coefficient for measured radioactivity concentration compared with the actual concentration was .97. In 13 meningiomas the correlation between in vivo SPECT measurements of uptake and in vitro measurements in samples of the same tumors removed surgically was .84; when two tumors that contained regions of necrosis and fibrosis were excluded it was .93. This method can be used for in vivo quantitative assessment of pharmacokinetics of labeled drug uptake in human brain tumors.

Evaluation Studies as Topic↗

Human lung tumors: SPECT quantitation of differences in Co-57 bleomycin uptake.

A newly developed single photon emission computed tomography (SPECT) method was used to measure noninvasively the concentration of labeled drugs in human lung tumors. The validity of the method was established by the high correlation (r = .92) between in vivo SPECT measurement of the concentration of glucoheptonate labeled with technetium-99m and in vitro measurement of the concentration of the drug in specimens of nine of the same tumors obtained at surgery. The in vivo concentration of intravenously injected bleomycin labeled with cobalt-57 was measured over time in 14 human lung tumors. Significant differences were found in the uptake of bleomycin by the tumors, even those with the same histologic characteristics, when the concentration over time, the tumor/blood ratio at 30 minutes, and the tumor cumulative concentration were measured in vivo. Since the drug concentration in the blood was not related to the concentration in the tumor (r = .54), uptake of chemotherapeutic drugs should be measured in each patient individually.

Adenocarcinoma↗

Monitoring of 57Co-bleomycin delivery to brain metastases and their tumors of origin.

The concentration of cobalt-57 (57Co)-labeled bleomycin delivered to three brain metastases and to their tumors of origin in the lungs was measured using a single-photon emission computerized tomography technique. In two brain metastases the 57Co-bleomycin concentration measured at different times after the intravenous injection was significantly lower than that in the originating lung tumors (p less than 0.01 and p less than 0.001). In these two patients, the tumor cumulative concentration (TCC) of drug in the brain neoplasm compared to the lung carcinoma was 12.92 versus 15.12 and 10.30 versus 19.74 micrograms/cc/min. In the third patient there was no significant difference in drug concentration between the tumor in the brain and in the lung (TCC 16.02 vs. 15.09 micrograms/cc/min). There was a significant difference in the drug TCC between the three brain metastases: the difference between the lowest and highest concentrations was more than 50% (10.3 vs. 16.02 micrograms/cc/min). When the concentration in the tumor over time (CT(t)) of the 57Co-bleomycin was compared in the brain and lung tumors, a good correlation was found in each of the three cases (r = 0.93, 0.99, and 0.97). This suggests that the difference in drug uptake between brain metastases and their originating lung tumor is a quantitative rather than a qualitative phenomenon. The results show that the amount of drug to which brain metastases are exposed varies and may be very low in some tumors; therefore, effectiveness of drug delivery may play a role in the nonresponsiveness of brain metastases to treatment.

Bleomycin↗

Human sarcoma-associated murine monoclonal antibody labeled with indium-111, gallium-67, and iodine-125.

Monoclonal antibody (MAb) 23H7 is a hybridoma-derived IgG that is generated following fusion of mouse myeloma cell line P3U1 and spleen cells from BALB/c mice hyperimmunized with a human fibrosarcoma. It detects a mesenchymal antigen of 23KD expressed on human sarcoma tissues and other neoplasms, including myeloid leukemias, but it rarely binds to normal tissues. The MAb 23H7 was labeled with 67Ga and 111In using the bifunctional ligand method. The 67Ga was chelated to the MAb via desferrioxamine B, while 111In was chelated via the cyclic anhydride of diethylenetriamine pentaacetic acid. Higher specific activity was obtained with 67Ga than with 111In (4.5 and 2 muCi/microgram, respectively); both gave stable complexes. When 23H7 was labeled with 125I, considerable breakdown was observed. This, together with the physical shortcomings of this isotope, emphasizes the advantages of labeling with 111In and 67Ga. The rapid blood clearance of the labeled sarcoma-associated MAb may be beneficial for early tumor uptake and for imaging shortly after injection.

Animals↗

Decrease in global ejection fraction after volume challenge in long-standing hypertension.

An easy noninvasive volume challenge method which takes advantage of the diastolic filling differences existing between patients with recent onset and long-standing hypertension is presented. By passively elevating the patients' legs at 45 degrees for 5 minutes, a sudden increase in venous return was induced in 14 healthy and in 42 hypertensive subjects. The global ejection fraction measured by radionuclide ventriculography increased markedly in both 14 normal subjects and in 18 patients with recent onset hypertension (67 +/- 9% to 75 +/- 6%, p less than 0.001 and 64 +/- 10% to 71 +/- 11%, p less than 0.001, respectively). In contrast, a decrease in global ejection fraction was found in all patients with long-standing hypertension (66 +/- 4% to 58 +/- 10%, p less than 0.001). Similar results were obtained when echocardiographic measurements were made after the legs-up procedure in 24 patients. The correlation with the radionuclide measurements done in the same patients was excellent, r = 0.89. In 20 patients with long-standing hypertension in whom exercise radionuclide ventriculography was done, a marked elevation in global left (LVEF) and right ventricular ejection fraction (RVEF) was found (65 +/- 5% to 71.5 +/- 11% LVEF, and 42 +/- 5% to 45 +/- 7% RVEF, p less than 0.01), whereas the legs-up procedure induced a significant reduction in both global LVEF and RVEF (65 +/- 5% to 57 +/- 6% LVEF, and 44 +/- 7% to 37 +/- 5% RVEF, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Superior sagittal sinus thrombosis: assessment with Tc-99m labeled red blood cells.

The diagnostic value of scintigraphy with technetium-99m labeled red blood cells (Tc-RBC) was assessed in 19 patients with clinical suggestion of superior sagittal sinus thrombosis (SSST). Comparison of Tc-RBC static images with dynamic flow studies in the brain showed a sensitivity of 100%, specificity of 86%, and accuracy of 94% for static studies and values of 87%, 20%, and 61%, respectively, for the flow studies. Tc-RBC scintigraphy enables direct visualization of the integrity of the superior sagittal sinus, whereas CT scanning shows various but nonspecific changes in the brain associated with SSST. Single-photon emission CT study using Tc-RBC, performed in six patients, appears to have potential in the diagnosis of SSST, allowing separation of vascular structures that are superimposed on the superior sagittal sinus in planar scintigraphy study.

Adolescent↗

Improved radionuclide method for assessment of pulmonary artery pressure in COPD.

An improved method of noninvasive assessment of pulmonary arterial pressure is presented. The already existing radionuclide method for assessment of pulmonary arterial pressure based on right ventricular ejection fraction, although having a relatively good positive predictive accuracy (75 percent), lacks in specificity and correlates only weakly with pulmonary arterial pressure, r = .66. In the present study a diastolic index of the ventricular performance (right atrial early diastolic emptying rate) was used to improve the predictive value of the right ventricular ejection fraction. Phase image analysis was used to differentiate the right atrium from the rest of the cardiac structures, and right atrial emptying rate was calculated after time activity curves were generated. A reasonably good correlation was found between right atrial emptying rate and pulmonary arterial pressure, r = .75. This diastolic index, however, was limited in its ability to detect patients with COPD and normal pulmonary arterial pressure (negative predictive value 62 percent). In order to improve the predictive value of right ventricular ejection fraction, having low specificity (33 percent) but high sensitivity (93 percent), a score index was constructed, combining right ventricular ejection fraction with right atrial emptying rate (having high specificity 100 percent, but modest sensitivity 78 percent). Score index proved to be an excellent indicator of pulmonary arterial hypertension (positive predictive value 93 percent, negative predictive value 100 percent.

Adult↗

Quantitative analysis of tight junctions and the uptake of 99mTc in human gliomas.

The structural dimensions of capillary tight junctions and the uptake of 99mTc pertechnetate in human gliomas were studied. Quantitative analysis revealed a correlation between the uptake of radionuclides and the length of endothelial tight junctions. It is suggested that brain scintigraphy might be used for the selection of malignant brain tumors with altered tight junctions which might be accessible to chemotherapy with water-soluble agents.

Blood-Brain Barrier↗

Scintigraphic findings in Gaucher's disease.

Gaucher's disease involves the liver, the spleen, and the bone. Liver-spleen and bone scintigraphy were used during an 8-yr period to evaluate changes caused by this disease. Patients were investigated with a liver-spleen scan for abdominal pain, mechanical discomfort, enlarged liver or spleen on physical examination, abdominal mass, abnormal liver function tests, and symptoms of hypersplenism. Fourteen liver-spleen scans were performed in nine patients. Liver scintigraphy showed various degrees of enlargement and inhomogeneous uptake. In two patients focal defects were detected. In one, focal defects were due to liver involvement with Gaucher's disease, but in the other they were caused by metastatic pancreatic carcinoma. The study was also useful in detecting splenic infarction and in following enlargement of the spleen after partial splenectomy. The main indication for bone scintigraphy in six patients was bone pain. This was found to be caused by either aseptic necrosis of the head of the femur, bone infarction, pathological fractures, or osteomyelitis. Loosening after total hip replacement was ruled out in three patients and missed in one patient. Scintigraphy appears to be a simple, sensitive test for evaluation of the liver, spleen, and bony skeleton in patients with symptomatic Gaucher's disease.

Bone Diseases↗

Early detection of diastolic impairment in long-standing hypertension by a noninvasive volume challenge method.

A simple, easily reproducible, noninvasive, provocative test for the assessment of early diastolic impairment in long-standing hypertension is presented. Volume challenge of the heart was produced by elevating the subject's legs to 45 degrees for 5 minutes, thus increasing the venous return to the right heart. Using gated radionuclide ventriculography and Fourier analysis, the atrial structures were delineated and time-activity curves were generated. Early diastolic emptying slope of the left atrium was used to assess left ventricular compliance changes in hypertensives. The left atrial early diastolic emptying rate was markedly reduced in 38 hypertensive patients (45.5 +/- 15.4 counts/s) when compared with 14 healthy subjects (78 +/- 16 counts/s). The legs-up procedure induced subsequent decrease in left atrial emptying rate in patients with long-standing hypertension and left ventricular hypertrophy (-27.4 +/- 11%). In patients with recent onset hypertension there was a depressed early diastolic emptying rate (55.79 +/- 10 counts/s), but a "normal" response to the legs-up procedure (an increase in left atrial emptying rate: 12.84 +/- 7%). Global ejection fraction was normal in all subjects studied, decreasing after induction of augmented venous return in long-standing hypertension. Reduction in left atrial early diastolic emptying rate, caused by the legs-up manoeuvre appears to be an early and sensitive indicator of the left ventricular diastolic impairment in essential hypertension.

Blood Volume↗

Stress fractures and bone pain: are they closely associated?

The relationship between bone pain and stress fractures diagnosed by bone scintigraphy was investigated in military recruits during active training. In three patients pain appeared in the site of abnormal uptake 7-14 days after the bone scan in a previously asymptomatic site. One hundred and twenty-four sites of stress fractures were found in 64 patients; 32 (26 per cent) were asymptomatic. In 38 patients (59 per cent) there were multiple stress fractures; 32 (33 per cent) had asymptomatic stress fractures. Fifty-three per cent of the regions with abnormal uptake in the femur were painless, compared with 17 per cent in the tibia. The necessity for imaging all bones susceptible to stress fractures, even when asymptomatic, is stressed. It is suggested that diagnosis of stress fracture should be made when typical abnormal uptake appears on scintigraphy. Bone pain in such cases may be delayed.

Adolescent↗

24-Hour/4-hour ratio of technetium-99m methylene diphosphonate uptake in patients with bone metastases and degenerative bone changes.

The uptake of [99mTc]MDP in metastatic lesions of the vertebrae was compared with the uptake in normal vertebrae. The ratio of these lesion-to-nonlesion uptakes at 4 and 24 hr was called the 24-hr/4-hr ratio (TF ratio). A similar ratio was measured for lesions in the spine due to degenerative bone disease. Lesions in vertebrae with degenerative bone disease and treated metastases had a significantly lower TF ratio than lesions in vertebrae with untreated bone metastases. These findings suggest that the TF ratio might be a reliable method for separating metastatic lesions from degenerative changes in the vertebral column, and could be especially useful in cancer patients whose bone scans demonstrate a single lesion in the spine.

Adult↗