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D Front

Publications and source records attributed to D Front.

At least 37 records · Page 2Linked to original sources

Blood-brain barrier permeability of human gliomas as determined by quantitation of cytoplasmic vesicles of the capillary endothelium and scintigraphic findings.

The number of cytoplasmic vesicles in the capillary endothelium was determined by ultrastructural morphometry and correlated with the uptake of technetium-99m pertechnetate used in brain scintigraphy. Ten gliomas were studied for uptake rates of 99mTc pertechnetate. Three gliomas from the different groups of uptake rates were quantitatively analyzed for cytoplasmic vesicle content. Capillaries of tumors without uptake had a low content of cytoplasmic vesicles, which was similar to that obtained in normal brain control. In tumors with low and moderate uptake rates, the cytoplasmic vesicles content increased significantly (p less than 0.05) by about 300% and 400%, respectively, as compared with that found in impermeable tumor and in normal brain. The correlation found between the cytoplasmic vesiculation of the endothelial cells in gliomas' capillaries and the uptake of 99mTc pertechnetate suggests that pinocytosis might be a factor in the uptake of the radionuclide. The present findings might be applicable to treatment with hydrophilic chemotherapeutic agents in moderate and highly permeable tumors.

Blood-Brain Barrier

Quantitation of renal uptake of technetium-99m DMSA using SPECT.

Quantitative single photon emission computed tomography (SPECT) methodology based on calibration with kidney phantoms has been applied for the assessment of renal uptake of [99mTc]DMSA in 25 normals; 16 patients with a single normal kidney; 30 patients with unilateral nephropathy; and 17 patients with bilateral nephropathy. An excellent correlation (r = 0.99, s.e.e. = 152) was found between SPECT measured concentration and actual concentration in kidney phantoms. Kidney uptake at 6 hr after injection in normals was 20.0% +/- 4.6% for the left and 20.8% +/- 4.4% for the right. Patients with unilateral nephropathy had a statistically significant (p less than 0.001) low uptake in the diseased kidney (7.0% +/- 4.7%), but the contralateral kidney uptake did not differ from the normal group (20.0% +/- 7.0%). The method was especially useful in patients with bilateral nephropathy. Significantly (p less than 0.001) decreased uptake was found in both kidneys (5.1% +/- 3.4% for the left and 6.7% +/- 4.2% for the right). The total kidney uptake (right and left) in this group showed to be inversely correlated (r = 0.83) with serum creatinine. The uptake of [99mTc]DMSA in single normal kidney was higher (p less than 0.001) than in a normal kidney (34.7% +/- 11.9%), however, it was lower than the total absolute uptake (RT + LT = 41.5% +/- 8.8%) in the normal group. The results indicate that SPECT is a reliable and reproducible technique to quantitate absolute kidney uptake of [99mTc]DMSA.

Adolescent

Quantitative bone scintigraphy using SPECT.

A quantitative single photon emission computed tomography (SPECT) technique for measuring radiopharmaceutical uptake in humans has been applied to bone scintigraphy. The method was validated by comparing SPECT measured percent of injected [99mTc]MDP in 16 normal skulls with well counter measurements of samples of the same bones obtained at surgery. A very good correlation (r = 0.96) was found. A very good interobserver correlation (r = 0.99) and agreement were also obtained when using quantitative bone scintigraphy (QBS). Control SPECT studies of uptake in the right and left iliac bones and the right and left sacroiliac regions in each patient showed no significant differences between the contralateral sides. Studies done in seven subjects at 2 and 4 hr after the same injection and in nine subjects 4 to 8 mo later in the same subjects showed a very good agreement and no significant differences between the two measurements were found. QBS is suggested as an accurate and reproducible index for assessment of the mass of remodeling bone. Preliminary results showed differences in QBS of normal subjects at different ages. A group of 68 young patients aged 18-26 yr showed a significant higher QBS (p less than 0.001) when compared to an older group of 62 patients aged 50-85 yr. There was, however, a wide range of uptake values for the same bone in the same group, suggesting that the method should best be used for following individual patients over time.

Adult

Radionuclide ventriculography and central aorta pressure change in noninvasive assessment of myocardial performance.

Systolic pressure-volume diagrams were obtained noninvasively by measuring the systolic central aortic pressure with a new device and by combining the pressure measurements, thus obtained, with absolute volume measurements obtained by radionuclide ventriculography during ejection. By dividing the peak power by the time elapsed from the beginning of ejection to the peak power point, the ejection rate of change of power (ERCP) was calculated. The ability of this index to assess left ventricular function at rest and exercise was evaluated in ten healthy subjects. ERCP proved to be more sensitive than global left ventricular ejection fraction increasing fivefold from rest to exercise compared with only 20% increase in global ejection fraction. ERCP increased dramatically postexercise from 3411 +/- 2173 to 18,162 +/- 14,633 gm/sec2, median 12,750, 95% confidence interval 9700-29,600, in healthy, while in patients it increased twofold from 2637 +/- 824 to 5062 +/- 1897 gm/sec2, median 4070, 95% confidence interval 2800-7030, p less than 0.001. ERCP had an excellent discriminative power in differentiating healthy subjects from patients, having 100% sensitivity, 90% specificity, 95% accuracy, 95% positive predictive value, and 90% negative predictive value. Thus, this noninvasive index seems to have a more comprehensive ability to evaluate changes in left ventricular function and shows a promising potential for clinical applications.

Adult

Gallium 67 imaging in monitoring lymphoma response to treatment.

The value of gallium 67 (Ga) imaging in monitoring lymphoma response to treatment was assessed in 25 patients with Ga-avid tumors and compared to body computed tomography (CT), chest radiographs, and palpation of tumor infiltrated peripheral lymph nodes. Ga imaging was negative in 95% (20/21) of the patients who were clinically considered to be in remission and in whom treatment was stopped. The disease did not recur during a follow-up of 12 to 26 months in 15 patients. Six patients developed recurrence of the disease 3 to 12 months after treatment was stopped. In all six patients Ga imaging became positive again at the time of the appearance of active disease. In the group of patients in remission, CT was negative in 57% (11/19), chest x-rays in 55% (6/11) and peripheral lymph nodes were palpated in none of the patients (13/13). In four patients that did not achieve remission after treatment, Ga scans were positive. Ga imaging appears useful in monitoring lymphoma response to treatment. This is probably because Ga imaging monitors tumor cell viability, whereas body CT and chest radiographs show the tumor mass, which may consist of fibrotic or necrotic tissue.

Adolescent

SPECT quantitation of cobalt-57 bleomycin delivery to human brain tumors.

A newly developed and validated noninvasive quantitative SPECT method was used to measure the in vivo uptake of [57Co]bleomycin (Co-bleo) in 13 human brain tumors and the uptake of [99mTc]glucoheptonate (GH) in 23 brain tumors. Significant differences in tumor uptake were found. The tumor concentration over time, the tumor to blood radio at 30 min and the tumor cumulative concentration of radioactivity showed marked differences even between tumors with the same histology. Only a weak correlation was found between tumor concentration of Co-bleo and of GH. Therefore a simple imaging agent such as GH cannot, at the present time, serve as an indicator of individual tumor uptake and further experience with other agents is still necessary. Contrary to the generally held view, no correlation was found between the concentration of drug in the blood and its tumor concentration. It is suggested therefore that the level of a drug in the blood cannot be used as a criterion of the amount that will penetrate the tumor. Direct SPECT measurement of the concentration of the drug in the tumor itself should be performed. The bioavailability of a drug is critical in order for it to exert it tumoricidal effect. The results, showing marked differences in uptake between brain tumors, suggest that before chemotherapy is administered, uptake of the chemotherapeutic drug in the individual tumor to be treated should be assessed and comparisons should be made between the uptake of a series of drugs to determine which drug would be most efficacious on the basis of its uptake as well as its tumor cell killing potential.

Biological Availability

Normal and abnormal single photon emission computed tomography of the skull: comparison with planar scintigraphy.

Using a rotating gamma camera the normal single photon emission computed tomography (SPECT) anatomy of the skull was defined in eight subjects. The value of SPECT as compared with planar scintigraphy was assessed in 34 patients with known or suspected disease of the skull. Seven patients had normal planar scintigraphy and SPECT. In 12 of 27 patients with bone involvement SPECT and planar scintigraphy showed essentially the same findings. In 15 patients SPECT was superior to planar scintigraphy. In three of these patients SPECT detected lesions while planar scan was normal. In the other 12 patients SPECT showed better anatomic localization and defined the full extent of the lesion. This was most obvious in patients with involvement of sphenoid, petrous, clivus, maxilla, and zygomatic bones. Our findings confirm the potential of SPECT to detect lesions in deep bones that are overlapped by superficial bony structures that cannot be visualized clearly with planar scintigraphy.

Bone Diseases

Method for noninvasive measurement of central aortic systolic pressure.

A method for noninvasive generation of central aortic systolic pressure curves is presented. The method is based on plotting the occlusive pressure values applied at the brachial artery level against the time intervals needed for the aortic pressure wave to equalize and break through the occlusive pressure at the brachial artery level. These time intervals were obtained by measuring the time from the beginning of depolarization (the QRS complex) to the detection of the pressure wave at the temporarily occluded brachial artery. The validity of the method was documented by 3 different approaches. The pressure values measured by a device developed by us were superimposed on the simultaneously measured central intra-aortic pressure waves and all values were within one standard deviation from the central aortic recordings in 8 of the 10 patients studied. At the same time, the noninvasively recorded pressure waves were completely different from the peripheral artery pressure recorded simultaneously at the femoral artery site. The DP/DT values derived from the central aortic recordings and the noninvasive device correlated (r = 0.83). These results indicate that the noninvasive device measures the central aortic pressure or a close approximation of it. By combining noninvasive pressure measurements with volume measurements obtained by radionuclide angiography, noninvasive pressure-volume curves were generated in 10 subjects. Possible clinical application of the systolic noninvasive pressure-volume curves is suggested.

Aorta

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