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Biomedical subjects

W D Kaplan

Publications and source records attributed to W D Kaplan.

At least 55 records · Page 3Linked to original sources

Thallium-201 brain tumor imaging: a comparative study with pathologic correlation.

In patients with gliomas who were stable or improving, we noted a disparity between clinical status and computed tomography (CT) brain scan results. To elucidate this finding, 29 patients were sequentially scanned with 2.0 mCi of 201Tl (5-30 min), 20 mCi [99mTc]gluceptate (GH) (3-4 hr) and 7-10 mCi 67Ga (48-72 hr). A total of 198 images were obtained. A set of three scans at a midpoint in follow up was selected for analysis. Seven patients who died had neuropathologic data available; brain sections were reconstructed to match radionuclide views without knowledge of image results. In the seven patients with autopsy data, 201Tl offered the most accurate correlation with viable tumor. Gallium-67 gave similar results in patients not receiving steroids. Technetium-99m GH scans could not allow differentiation between tumor, necrosis, and edema. Similarly, the CT scan could not routinely differentiate between fibrotic, nonfibrotic, necrotic, and neoplastic tissue. In the 22 patients without autopsy data, 201Tl scans commonly showed smaller and more focal abnormal uptake when compared with [99mTc]GH and 67Ga scans. Thallium-201 scans more accurately reflect viable tumor burden than other radionuclide studies of primary brain tumors, are minimally affected by concomitant steroid administration, can be performed immediately following tracer administration, and complement the anatomic data obtained from CT scans.

Adolescent↗

Radioiodinated B6.2 monoclonal antibody: further characterization of a potential radiopharmaceutical for the identification of breast tumors.

A monoclonal antibody (B6.2) directed against human breast carcinomas and its F(ab')2 and Fab' fragments were labeled with 125I using Iodogen. Solid phase radioimmunoassay was used to evaluate the in vitro binding of the labeled antibodies to a human breast tumor metastasis to the liver, the MCF-7 breast tumor cell line and normal liver tissue. Scatchard analysis revealed that 125I-labeled B6.2 IgG and F(ab')2 bound to both breast tumors with affinity constants in the range 1.2-4.4 X 10(9) M-1, while the affinity constant for the binding of the 125I-labeled Fab' fragment to the metastasis and the MCF-7 line was 5.9 and 9.1 X 10(8) M-1, respectively. Serial blood sampling indicated that blood clearance of 125I activity decreased with increasing protein size. A comparison of tumor-to-tissue ratios at two doses of 125I-B6.2 IgG and F(ab')2 suggests that the optimal dose of antibody may depend on the imaging time. A comparison of the blood clearance of 125I activity following injection of 125I-B6.2 and nonspecific 125I-MOPC 21 demonstrated that the specific antibody cleared much more rapidly. When 125I-B6.2 was injected into mice bearing either breast or melanoma tumors, the thyroid uptake of 125I was significantly greater in mice with breast tumors. These results suggest that the catabolism of radiolabel from the specific antibody in the presence of tumor is greater and that this may be an important factor in determining the optimal radiolabel for immunoscintigraphy.

Animals↗

Clinical significance of solitary rib lesions in patients with extraskeletal malignancy.

A retrospective review of 2,851 bone scans done at a cancer center over a period of 4 yr revealed 41 patients having a single abnormality in a rib as their first abnormal scintigraphic finding. The scan findings in these cases were correlated with clinical, scintigraphic, and radiographic follow-up to ascertain their etiology and course. Four lesions (9.8%) were due to malignant disease, 16 (39%) were associated with benign fractures demonstrated on x-ray, 11 (27%) were associated with primary or postoperative radiation therapy. The remaining ten patients (24.2%) with normal x-rays and no association with radiation therapy or subsequent development of metastasis were assigned to benign etiology. This experience suggests that solitary rib lesions in cancer patients are uncommon and are most frequently (90%) associated with benign etiology.

Bone Diseases↗

Clinical comparison of two radiocolloids for internal mammary lymphoscintigraphy.

Recent studies suggest that 99mTc-labeled radiocolloid (SC) compounded with hydrogen sulfide can be used to visualize lymph channels and nodes. Our study prospectively compared SC with 99mTc antimony sulfide (SbS) colloid, in 28 patients undergoing internal mammary lymphoscintigraphy. Images were recorded on a scintillation camera and computer at 0.5, 1.0, and 3.0 hr. Quantitative analysis included assessment of percent (%) injected dose in nodes, the percent remaining at the injection site, and the relative intensity of the most cephalad node compared to a 57Co standard. The mean (means) % injected dose of both radiocolloids within visualized nodes was less than 1% at each time interval, with no significant differences between means's. The means % injected dose remaining at the injection site at 3.0 hr was 83 for SbS and 76 for SC not statistically significant (N.S.). The means of the ratio of counts within the most cephalad node at 3.0 hr to counts within a 57Co standard was 0.98 for SbS and 1.03 for SC (N.S.). Clinical assessment of number of nodes visualized and extent of radiocolloid migration showed no difference between the two agents. The biological and clinical parameters for the two colloids appear similar when used for internal mammary lymphoscintigraphy.

Adult↗

Role of 99mTc methylene diphosphonate bone imaging in the management of lymphoma.

The role of modern techniques of 99mTc methylene diphosphonate bone imaging in the management of lymphoma patients was assessed by comparing results of 107 bone scans in 16 patients with Hodgkin's disease, and 45 patients with non-Hodgkin's lymphoma to simultaneous radiologic, clinical, and histopathologic features as well as to subsequent disease course. The sensitivity and specificity were both greater than or equal to 0.96 in both Hodgkin's disease and non-Hodgkin's lymphoma and the overall accuracy by site was 98%. The scan proved to be useful in the definition and follow-up of skeletal lymphomatous disease in both symptomatic and asymptomatic patients, and defined abnormalities which were not predicted by either serum alkaline phosphatase activity or the presence of bone marrow involvement. In no patient, however, did the bone scan result by itself alter either initial staging or estimates of extent of disease at the time of relapse. Bone scanning, therefore, cannot be recommended as a screening procedure in patients with lymphoma; rather, this test is best reserved for the definition and follow-up of skeletal metastases in patients with active, concomitant, extraosseous disease.

Bone Neoplasms↗

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↗

Uptake of 99mTc-MDP by pseudomyxoma peritonei: a case report.

A patient with pseudomyxoma peritonei secondary to a mucin-secreting adenocarcinoma demonstrated striking, diffuse uptake of 99mTc-MDP throughout the abdomen. The radiopharmaceutical distribution accurately delineated the region of tumor involvement within the peritoneal cavity.

Adult↗

High-dose gallium imaging in lymphoma.

The role of gallium-67 imaging in the management of patients with lymphoma, traditionally assessed using low tracer doses and the rectilinear scanner, was assessed when using larger doses (7 to 10 mCi) and a triple-peak Anger camera. Gallium scan results in 51 patients with non-Hodgkin's lymphoma and 21 patients with Hodgkin's disease were compared with simultaneous radiologic, clinical, and histopathologic reports. Subsequent disease course was also evaluated in light of radionuclide findings. Sensitivity and specificity of the scans were 0.90 or greater for both non-Hodgkin's lymphoma and Hodgkin's disease, and overall accuracy by site was 96 percent. Although there are insufficient numbers of pretreatment scans to allow any conclusions, our data suggest that newer approaches to gallium scanning in treated patients are (1) highly specific in all lymphomas and most sensitive in high-grade non-Hodgkin's lymphoma and Hodgkin's disease; (2) valuable in assessing the mediastinum in both non-Hodgkin's lymphoma and Hodgkin's disease; and (3) helpful adjuncts to computed tomographic scanning and ultrasonography in assessing abdominal node disease.

Gallium Radioisotopes↗

Iliopelvic lymphoscintigraphy.

In patients with genitourinary cancers, it is critically important that lymph node metastases be detected prior to surgery. Information regarding the status of these nodes will influence the type and extent of therapy. Radiologic tests currently available for lymph node imaging--contrast lymphangiography, ultrasound, and computed tomography--are sometimes associated with a high false-negative rate. Iliopelvic lymphoscintigraphy, when performed following bilateral perianal injections of 99mTc-antimony trisulfide colloid, offers a physiologic method for visualizing these nodes and allows demonstration of the internal iliac chain, often not visualized on contrast lymphangiographic studies. Additionally, data from initial patient trials suggest that this technique offers a clinically acceptable level of sensitivity and specificity. This article details the methodology of the technique, and addresses reproducibility, sensitivity, specificity, and image interpretation.

Antimony↗

Iliopelvic radionuclide lymphoscintigraphy in patients with testicular cancer.

The utility of iliopelvic lymphoscintigraphy was assessed in 21 patients with testicular cancer (six seminoma patients, 15 nonseminoma patients). Normal lymphoscintiscans demonstrated symmetric uptake of technetium-99m-labeled radiocolloid throughout the lymphatic chain, from the internal iliac nodes to the level of the renal hilum. Signs of abnormality included decreased or no uptake of radionuclide in consecutive nodes of a lymphatic chain or in an entire lymphatic chain, and diminished uptake at the level of the renal hilum. In the 15 patients with nonseminomatous germ cell cancer, correlation of the results of scanning with pathologic specimens obtained upon dissection of retroperitoneal lymph nodes revealed a sensitivity of 0.89 and a specificity of 0.83. In the six patients with seminoma, there was good correlation between scan findings and results of other radiologic tests. This study suggests that iliopelvic lymphoscintigraphy is a sensitive means of determining whether lymph node metastases are present in patients with testicular cancer.

Abdomen↗

Long-term hepatic arterial infusion of 5-fluorodeoxyuridine for liver metastases using an implantable infusion pump.

Twenty-one patients with liver metastases of various histologies (predominantly colorectal carcinoma) underwent Infusaid pump implantation for long-term hepatic arterial 5-fluorodeoxyuridine (5-FUdR) infusion. Patients received 5-FUdR infusion on a 2-wk cycle alternating with a 2-wk saline--heparin infusion. A dosage of 0.2-0.3 mg/kg/day (average 0.23 mg/kg/day) was infused for a cumulative 5-FUdR administration of 1940 days. Six patients (29%) responded to therapy (five colorectal, one carcinoid); median response duration was 6 mo. Median survival for the treated group was 17 mo from diagnosis of liver metastases and 13 mo from pump implantation. Median survival among the six responding patients was 15 mo from diagnosis of liver metastases and 11 mo from pump implantation. Comparison of survival from the diagnosis of liver metastases of the treated group to ten patients found ineligible for the study by virtue of extrahepatic metastases revealed no significant difference in median (18 mo for ineligible group) or overall survival. However, median survival for the treated group after pump implantation (13 mo) was significantly better than the median survival of the ineligible group after evaluation for this study (4 mo). Toxicities of therapy included fatigue, anorexia, nausea, vomiting, toxic hepatitis, epigastric pain, and diarrhea. No patients died of toxicity, but six patients required hospitalization for management of pain or vomiting. No serious technical complications developed in any patient except separation of the infusion catheter at its junction with the pump in one patient, necessitating pump replacement for continuation of therapy. These survival data suggest identification of new anticancer agents for hepatic arterial infusion.

Adult↗

Utilization of parasternal lymphoscintigraphy in radiation therapy of breast carcinoma.

In radiation therapy of patients with breast carcinoma, the ipsilateral internal mammary lymph nodes are either irradiated by a separate anterior field or included by isocentric opposing tangential fields, which also treat the breast and chest wall. To determine the acceptability of a particular treatment setup, the positions of the nodes must be determined with respect to the treatment fields. For the anterior field technique the problem is two-dimensional and is solved by simply superimposing the treatment field onto an anterior lymphoscintigram. For treatment by opposing tangential fields the problem is three-dimensional and more complex. The solution described in this note is to project the three-dimensional lymph node positions, obtained by a stereo-lymphoscintigraphic procedure, onto the tangential field radiographs. A mathematical expression is given to perform the required projection of the node positions onto the radiographs.

Breast Neoplasms↗

Therapeutic intraperitoneal 32P: a clinical assessment of the dynamics of distribution.

With an Anger camera for scintigraphic recording of bremsstrahlung radiation from phosphorus-32, the distribution of intraperitoneal colloidal chromic phosphate was followed in patients with gynecologic tumors. Sequential pelvic, abdominal, and thoracic scintiphotos over a three-week period revealed rapid and persistent focal aggregation of the radiocolloid with no change in pelvic or peritoneal radionuclide distribution patterns. Visualization of intrathoracic lymph node uptake did not correlate with the presence of diaphragmatic tumor. This study demonstrates the utility of scintigraphy for monitoring the distribution of intraperitoneal beta emitters and the need for developing alternative methods of administering these therapeutic agents to achieve more uniform patterns of distribution.

Brachytherapy↗

Inhalation patterns and predominant site of bronchoconstriction in healthy subjects.

To determine the relationship between changes in density dependence of maximal expiratory flow and changes in the predominant site of bronchoconstriction, we altered the pattern of inhalation of a methacholine aerosol to achieve deposition either centrally (by short choppy breaths) or peripherally (by slow deep breaths). Partial expiratory flow volume curves on air and on 80% helium-20% oxygen (HeO2) were recorded in six healthy subjects before and after each pattern of methacholine inhalation. We varied concentrations of methacholine and number of inhalations to achieve equivalent degrees of bronchoconstriction as assessed by decreases in maximal flow (Vmax) on air, which fell 27% from control values. Vmax on HeO2 also fell after both inhalation patterns. Density dependence (Vmax on HeO2 divided by Vmax on air) decreased following slow deep breaths of bronchoconstrictor aerosol, and increased following short choppy breaths. In three subjects, inhalation of radiolabeled methacholine aerosol confirmed that the slow deep pattern was associated with a diffuse, more peripheral deposition, whereas the short choppy pattern led to central deposition. We conclude that changes in density dependence reflect the predominant site of obstruction after acute methacholine aerosol challenge in healthy subjects.

Adult↗

Mediastinal lymphoscintigraphy in ovarian cancer using intraperitoneal autologous technetium-99m-labelled erythrocytes.

99Tcm-labelled autologous erythrocytes (approximately 2.0 ml and 2.0 mCi) were administered intraperitoneally (IP) to 15 patients with ovarian cancer. Anterior abdominal images were then collected for up to six hours to evaluate both the dynamics of intraperitoneal tracer distribution and the potential for visualizing internal mammary lymph nodes as correlated with the presence of diaphragmatic tumour. Results indicated that dispersion of red cells closely resembled that seen during IP contrast studies; the distribution patterns were heterogeneous, remained constant with time, and were intimately related to bowel peristalsis. Visualization of internal mammary lymph nodes indicated patency of diaphragmatic lymphatics; non-visualized nodes correlated with the presence of diaphragmatic tumour. The test had a sensitivity of 0.80 and a specificity of 0.90 for defining disease. Results of this study suggest use of 99Tcm-red blood cells as a diagnostic test for diaphragmatic involvement by ovarian cancer and as a method for monitoring the effects of therapy.

Diaphragm↗

The use and limitations of serial plasma carcinoembryonic antigen (CEA) levels as a monitor of changing metastatic liver tumor volume in patients receiving chemotherapy.

Nine patients with liver-predominant or liver-only metastatic adenocarcinoma, who received hepatic intra-arterial and peripheral intravenous chemotherapy, were evaluated to determine if changes in plasma CEA accurately indicated changes in liver tumor volume as estimated from serial liver scan defect sizes, and if the two were quantitatively related. When selected periods of tumor remission or progression were studied during chemotherapy, the index of change of serial CEA values correlated positively (r = 0.764, P = 0.01) with the index of change of liver tumor volume in all 9 cases. Changes in absolute CEA values, however, aid not correlate significantly with changes in absolute liver tumor volumes when assessed either during these selected periods or throughout individual patient courses. Biologic and methodologic factors that influence the quantitative relation between liver tumor volume and plasma CEA are discussed.

Adenocarcinoma↗