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Biomedical subjects

S D Yeh

Publications and source records attributed to S D Yeh.

At least 55 records · Page 3Linked to original sources

Radioimmunodetection of neuroblastoma with iodine-131-3F8: correlation with biopsy, iodine-131-metaiodobenzylguanidine and standard diagnostic modalities.

Iodine-131-3F8, a murine IgG3 monoclonal antibody specific for ganglioside GD2 was evaluated by radioimmunoscintigraphy in 42 patients with neuroblastoma. Comparison was made with 131I-metaiodobenzylguanidine (MIBG), 99mTc-methylene diphosphonate (MDP) bone scans, as well as computed axial tomography (CT) or magnetic resonance imaging (MRI). Iodine-131-3F8 detected more abnormal sites (283) than [131I] MIBG (138) or 99mTc-MDP (69), especially in patients with extensive disease. In 20 patients with soft-tissue tumors demonstrated by CT/MRI, 131I-3F8 detected the disease in 18. Upon surgical resection, two tumors interpreted as negative with 131I-3F8 imaging revealed ganglioneuroma, one showing microscopic foci of neuroblastoma. In contrast, 131I-3F8 imaging identified tumors that were confirmed histologically as neuroblastomas. In 26 patients with evidence of marrow disease by antibody scans, 14/26 had confirmation by iliac crest marrow aspirate/biopsy examinations. We conclude that 131I-3F8 scintigraphy has clinical utility in the management of patients with neuroblastoma by improving the sensitivity of tumor detection.

3-Iodobenzylguanidine↗

Quantitative analysis of antibody localization in human metastatic colon cancer: a phase I study of monoclonal antibody A33.

A33 is a mouse immunoglobulin G2a (IgG2a) monoclonal antibody (mAb) that detects a heat-stable, protease- and neuraminidase-resistant epitope. The antigen is homogeneously expressed by virtually all colon cancers and in the colon mucosa but not other epithelial tissues. The biodistribution and imaging characteristics of iodine-131 (131I)-mAbA33 were studied in colorectal carcinoma patients with hepatic metastases. Antibody labeled with 2 to 5 mCi of 131I was administered intravenously (IV) 7 to 8 days before surgery at five dose levels, ranging from 0.2 mg to 50 mg, with three or more patients entered at each dose level. In addition, three patients received 2 mg 131I-mAbTA99 (an isotype-matched control mAb) together with 125I-mAbA33. Evaluation included whole-body imaging with a gamma camera, technetium-99 (99mTc)-human serum albumin blood pool scans, liver/spleen scans, abdominal computed tomographic (CT) scans, hepatic arteriograms, antibody pharmacokinetics, and assessment of antibody distribution in biopsied malignant and normal tissues. Selective mAbA33 localization to tumor tissue was demonstrated in 19 of 20 patients, and external imaging correlated with surgical inspection, pathologic examination, and tissue radioactivity. One week after antibody administration, tumor:liver ratios ranged from 6.9:1 to 100:1 and tumor:serum ratios from 4.1:1 to 25.2:1. 99mTc-albumin blood pool studies showed that liver metastases were hypovascular, emphasizing the selective localization of mAbA33 despite poor tumor-blood flow. Control mAbTA99 studies showed mAbA33 localization was antigen-specific; tumor:liver ratios were 2.3- to 45-fold higher for specific antibody. In metastatic lesions, radioisotope was localized primarily in the viable periphery; however, even the necrotic tumor core concentrated specific antibody. External imaging showed isotope visualization in some patients' large bowel; whether this represents specific antibody uptake or gastric iodine secretion is unclear.

Adult↗

A phase I toxicity, pharmacology, and dosimetry trial of monoclonal antibody OKB7 in patients with non-Hodgkin's lymphoma: effects of tumor burden and antigen expression.

Eighteen patients with relapsed non-Hodgkin's lymphoma (NHL) were infused with escalating doses of monoclonal antibody (mAb) OKB7, trace-labeled with iodine-131 (131I), in order to study toxicity, pharmacology, antibody localization, and dosimetry of radioiodine. OKB7 is a noncytotoxic mouse immunoglobulin G2b (IgG2b) mAb reactive with B cells and most B-cell NHL. Three patients each were treated at six dose levels ranging from 0.1 mg to 40 mg. All patients had radionuclide imaging and counting daily, had serial blood sampling to study pharmacokinetics, human antimouse antibody (HAMA), and circulating antigen, and had a biopsy of accessible lymphoma to determine delivery of isotope to tumors and assess the effect of tumor antigen expression on mAb delivery. Bone marrow biopsies were also done in the majority of patients. There was no toxicity. Serum clearance showed a median early phase half-life of 1.9 hours and a later phase half-life of 21.7 hours. Median total body clearance half-life was 22 hours. Pharmacokinetics were not dose-related. HAMA was detected in five patients. Circulating blocking antigen was detected in the serum of four patients, but at levels that were of pharmacologic consequence only in one. Biopsied tumor tissue from five patients did not express OKB7 antigen. No significant uptake of antibody was seen in these tumor sites. Mean total uptake of isotope into lymphoma measured in biopsies correlated linearly over the 400-fold increase in injected mAb dose. However, the percent of injected dose found per gram of tumor was unrelated to dose, but correlated inversely with tumor burden. In two patients with minimal tumor burden, 1.0 mg and 5.0 mg doses of OKB7 resulted in tumor to body radioisotope dose ratios of 22 and 7, which would theoretically permit tolerable delivery of 4,400 and 1,400 rads to these tumors, respectively, if OKB7 were conjugated with higher doses of 131I.

Adult↗

Correlation between iodine-131 MIBG imaging and biological markers in advanced neuroblastoma.

I-131 metaiodobenzylguanidine (MIBG) imaging was performed in 38 patients with advanced neuroblastoma. Abnormal images were found in patients with elevations of urinary vanillylmandelic acid and dopamine and high serum neuron-specific enolase levels. Normal or minimal elevation of markers was seen in patients with negative images. In follow-up studies after chemotherapy, the disappearance of abnormal uptake was noted in those patients with normal marker values. A persistently abnormal uptake occurred in patients with high marker values. Conversion from a normal image to an abnormal image also occurred in patients whose markers became elevated. I-131 MIBG imaging is sensitive in detecting active foci of a neuroblastoma and is useful in monitoring chemotherapy in these patients.

3-Iodobenzylguanidine↗

Tc-99m diphosphonate uptake in malignant fibrous histiocytoma: a possible iron-related effect.

A man with malignant fibrous histiocytoma of the thigh had avid uptake of Tc-99m MDP in the lesion. Review of tissue sections showed considerable accumulation of iron in the tumor. Iron is known to be a potential nidus for deposition of the Tc-99m diphosphonates. A review was made of tissue sections from two other reported cases of malignant fibrous histiocytoma which also had significant accumulation of Tc-99m diphosphonates. Both revealed iron within the tumor. The origin of the iron is unknown (perhaps from necrosis and hemorrhage, from trauma, or from innate phagocytic activity of the histiocytes). However, this observation may serve as a stimulus to studies attempting to discern the underlying mechanisms of extraosseous deposition of the Tc-99m diphosphonates.

Adult↗

A complication of prolonged infusional chemotherapy masquerading as a bone metastasis in a patient with colorectal carcinoma.

A patient with metastatic colorectal carcinoma to the liver, who was being treated with a continuous systemic infusion of floxuridine (FUDR) through a permanent indwelling central venous catheter, developed bone pain. Bone imaging showed abnormal findings, without evidence of metastatic disease progression elsewhere. The patient's complaints and the abnormality seen on the bone scan resolved with removal of the catheter and discontinuation of the systemic infusion. Diagnostic and therapeutic considerations are discussed.

Adenocarcinoma↗

Imaging studies of patients with malignant fibrous histiocytoma using C-11-alpha-aminoisobutyric acid (AIB).

Alpha-aminoisobutyric acid (AIB), a synthetic, nonmetabolized amino acid which is rapidly transported into viable cells by the A-type or alanine-preferring amino acid transport system, has been labeled with the short-lived, positron-emitting radionuclide carbon-11. Carbon-11 labeled AIB is currently being evaluated as a tumor imaging agent for in vivo amino acid transport studies in patients with cancer. In this study, C-11 AIB was used to image two patients with malignant fibrous histiocytoma (MFH), a pleomorphic sarcoma. Following intravenous administration of C-11 AIB, tumors in the distal femur of one patient and in the anterior chest wall of another patient were well visualized using high energy gamma scintigraphy. Since therapy may alter the accumulation of amino acids in tumor tissue, studies using C-11 AIB in patients with MFH before and after chemotherapy are in progress.

Adult↗

Abnormal gallium scintigraphy in pulmonary alveolar proteinosis (PAP).

A patient with medulloblastoma of the cerebellum developed dyspnea and hypoxemia. Pulmonary function tests showed decreased lung volume and diffusing capacity, while the chest radiographs initially showed only mild interstitial infiltrates. Repeated gallium scans showed diffuse lung uptake and diagnosis of pulmonary alveolar proteinosis was made by open lung biopsy.

Adult↗

Simultaneous estimation of liquid and solid gastric emptying using radiolabelled egg and water in supine normal subjects.

To develop an additional method for the measurement of gastric emptying in supine subjects, 10 normal subjects were given a test meal containing 99Tc-labelled scrambled egg as the "solid" phase marker and 111In in tapwater as the marker for the "liquid" phase. The mean time for emptying 50% of the "solid" phase (t1/2) was 85 min and 29 min for the "liquid" phase. Three individuals were restudied with a mean difference between the two determinations of 10.8% for the "solid" phase and 6.5% for the "liquid" phase. Twenty-six additional studies attempted have been successfully completed in symptomatic patients with advanced cancer. This method provides a simple and reproducible procedure for the determination of gastric emptying that yields results similar to those reported for other test meals and can be used in debilitated patients.

Adult↗

Lymphoscintigraphic studies of lymphatic drainage from the testes.

Two colloidal radiopharmaceuticals, Au-198 and Tc-99m antimony, were used to evaluate the lymphatic drainage of the testis in experimental animals and humans. One to 24 hours after direct intratesticular injection of Au-198 colloid in dogs and 4-6 hours after injection of Tc-99m antimony colloid in men, distribution within retroperitoneal lymph nodes was demonstrated. Uptake within the para-aortic lymph nodes primarily draining the testis was decreased following proximal ligation of the spermatic vessels in dogs. Testicular lymphoscintigraphy successfully demonstrated an intact spermatic cord lymphatic communication to the para-aortic nodes in five of six patients with chronic lower-extremity lymphedema. When the intact testicle and spermatic cord were transposed to the thigh in a patient with chronic lymphedema of the lower extremity, percutaneous pedal lymphoscintigraphy successfully demonstrated uptake within the para-aortic lymph nodes draining the ipsilateral testis.

Adult↗

Long-term follow-up of cardiac function in patients with Hodgkin's disease treated with mediastinal irradiation and combination chemotherapy including doxorubicin.

Among 41 evaluable patients whose first treatment for advanced Hodgkin's disease had consisted of alternating cycles of mechlorethamine, vincristine, prednisone, and procarbazine (MOPP), and doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), in addition to low-dose mediastinal irradiation, 19 underwent retrospective cardiac evaluation by routine posteroanterior and lateral chest x-ray, 12-lead ECG, M-mode echocardiogram, and ECG-gated left ventricular blood pool scan at rest and during exercise. Fifteen patients had unequivocally normal left ventricular function by all these parameters. Two patients had minimally reduced left ventricular ejection fraction (LVEF) at rest with a normal increment with exercise. In two other patients with high normal resting LVEF and subnormal increment with exercise, the elevated resting values implied initial measurement in a nonbasal state. A twentieth patient (the oldest; one of two with active Hodgkin's disease at the time of evaluation and the stimulus for this study) had markedly reduced LVEF as determined by radionuclide cardiac angiography and had developed clinical congestive heart failure shortly before evaluation. Despite this patient, the study indicates that treatment with MOPP/ABVD and low-dose mediastinal irradiation entails low risk for cardiac complications.

Adult↗

Scintigraphic features of primary sacral tumors.

The bone scan features of different types of sacral tumors in 16 patients were assessed. Four out of five patients with chordoma, the most common sacral tumor, demonstrated either reduced uptake or normal distribution of isotope at the site of this midline tumor. Plasmacytoma, which is not usually central, also caused reduced uptake on the bone scan. Ewing's sarcoma gave no consistent pattern. All other tumors caused increased uptake except for one unusual case of osteogenic sarcoma. Bone scintigraphy can be very useful in the assessment of sacral tumors. A midline sacral tumor that is cold on the bone scan is very likely to be a chordoma.

Adolescent↗

Technetium-99m albumin scintigraphy in the diagnosis of protein-losing enteropathy.

While several studies have documented protein losing enteropathy by measuring the excretion of intravenously administered 131I- or 51Cr-labeled albumin, the efficacy of 99mTc-labeled albumin in detecting protein loss in the bowel has not been described. We report here a case of severe protein-losing enteropathy demonstrated by abnormal excretion of 99mTc albumin into the bowel.

Adult↗

Predicting tumor response in patients with colorectal hepatic metastases.

Until now, there has been no reliable means of predicting tumor response to chemotherapy in patients with metastatic colorectal cancer. Using arterial nuclide flow scans as a determinant of tumor response, the degree of tumor perfusion was evaluated in a blinded prospective study. Seventy-three patients with colorectal hepatic metastases received continuous hepatic arterial (N = 52) or systemic intravenous (N = 21) chemotherapy using an implantable pump. All patients had pretreatment hepatic arteriography and arterial flow scans using 99mTc macroaggregated albumin (99mTc-MAA). An arteriogram was characterized as positive if it showed tumor hypervascularity; the 99mTc-MAA flow scan was considered positive if it showed increased tumor uptake relative to the liver. Of 47 patients with an evaluable 99mTc-MAA flow scan who were treated with arterial infusion, 31 had a positive scan; in this group 16 responded to chemotherapy. The 99mTc-MAA scan was negative in 16 patients, of whom one responded to chemotherapy (p less than 0.006). The 99mTc-MAA scan had the greatest predictive value in previously untreated patients (sensitivity = 91%; specificity = 77%). The arteriogram was positive in 25 of 46 evaluable patients, but this finding had little predictive value for tumor response (sensitivity = 56%; specificity = 46%). Of 21 patients receiving systemic intravenous infusion, the scan was positive in nine patients, of whom seven responded to chemotherapy. The 99mTc-MAA scan was negative in 12 patients, of whom one responded to chemotherapy (sensitivity = 88%; specificity = 85%). When 99mTc-MAA-positive and -negative groups were compared, there were no differences in mean patient age, per cent liver involvement, tumor size, or plasma liver function tests. Hepatic tumor perfusion as determined by MAA arterial flow scan is a reliable predictor of tumor response in patients with metastases from large bowel cancer. The test provides a valuable criterion for selecting individuals for treatment of metastases from large bowel cancer by infusion chemotherapy.

Adult↗