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Biomedical subjects

E A Silverstein

Publications and source records attributed to E A Silverstein.

10 recordsLinked to original sources

A phase I escalating-dose safety, dosimetry and efficacy study of radiolabeled monoclonal antibody LYM-1.

Thirteen patients with relapsed or refractory Non-Hodgkin's Lymphoma were treated with 131I-Lym-1 during the course of a dose escalation trial. Principal aims were to establish the maximum tolerated single dose (MTD), as well as to assess clinical and dosimetric effects of the MTD. Patients were eligible if > 25% of tumor cells bound Lym-1 on immunohistochemistry, stain intensity was +2/4 or greater and human anti-mouse antibody (HAMA) assay was negative. Radioimmunotherapy was performed with escalating doses at levels of 50 mCi, 65 mCi/m2 and 80 mCi/m2 (50-139 mCi total). Patients were eligible for retreatment after 6-10 weeks if there was no severe toxicity, their disease was at least stable and HAMA remained negative. Three were retreated. Four have achieved partial responses which lasted 11, 11, 18 and 22 weeks. Acute toxicities included rigors (69%), fever (62%), nausea (46%), vomiting (46%), pruritus (23%), urticaria (23%), chest pain (23%) and bronchospasm (15%). HAMA developed in 3 patients. Myelosuppression, manifested as thrombocytopenia and neutropenia, was dose-limiting and defined the single dose MTD at 65 mCi/m2. Plasma radioactivity clearance was biphasic, with a 0.9 hr alpha-T1/2 and a 19.8 hr beta-T1/2. At completion of Lym-1 infusion, a mean of 45% of the injected dose was recoverable in the circulation. Images obtained within the first 2 hours indicated mean hepatic and splenic uptake was 29% and 11%, respectively. Radiation absorbed doses to tumor ranged from 18-61 rads; mean doses to whole body ranged from 17 to 71 rads.

Adult↗

Nuclear medicine imaging workstations based on personal computer technology.

The development of personal computer technology has resulted in extremely powerful, inexpensive computers available as consumer items. With the addition of suitable hardware for gamma camera interfacing and image display, such systems can be transformed into fully functional nuclear medicine computers capable of performing all of the acquisition and processing tasks required in a modern radioisotope imaging department. Such an approach to nuclear medicine computerization offers many advantages in terms of flexibility, speed, cost, and expandability.

Hospital Departments↗

Radioimmunotherapy of patients with cutaneous T-cell lymphoma using an iodine-131-labeled monoclonal antibody: analysis of retreatment following plasmapheresis.

Radioimmunotherapy retreatment of patients receiving radiolabeled murine monoclonal antibodies is difficult because of human antimurine antibody (HAMA) formation. Retreatment therapy was initiated in three patients at the time of disease progression using a radioiodinated monoclonal antibody (T101). The clinical protocol consisted of a two day plasma exchange (4-6 L) to reduce HAMA titers. Immunoimaging was performed with 5 mCi 131I-T101 (10 mg). Gamma scintillation images were obtained 18 hr postinfusion, and radiation dosimetry estimates were performed. At 24 hr postinfusion, each patient received a 100-mCi 131I-T101 (10 mg) therapy dose. Results obtained after plasmapheresis showed a significant reduction, ranging from 28%-61%, in HAMA titers. Blood clearances were markedly different between initial therapy and retreatment therapy for patient with high HAMA titers, reflecting immune complex formation. Two patients responded to retreatment therapy with responses lasting 1 to 2 mo. Minimal acute and no chronic toxicities were observed during the retreatment protocol.

Antibodies, Monoclonal↗

Considerations for tomographic imaging of monoclonal antibodies.

Monoclonal antibodies have begun to assume a significant role in clinical research. The ability to label these agents has initiated research in the areas of radioimmunodetection and radioimmunotherapy. In the case of antibodies directed against tumor antigens, imaging has been employed to help assess location and extent of disease, and to provide information and extent of disease, and to provide information concerning biodistribution to be used in subsequent dosimetric calculations. Because of the low counting statistics characteristic of such images, the use of single photon emission computed tomography (SPECT) is suggested as a potential method of improving the diagnostic yield from image data. Careful attention to acquisition parameters and image processing options is needed if these goals are to be achieved.

Antibodies, Monoclonal↗

Radioimmunoimaging of human small cell lung carcinoma with I-131 tumor specific monoclonal antibody.

In this study, an IgM monoclonal antibody (MAb600D11) directed against human small cell lung cancer (NCI-H69) was radiolabeled with iodine-131, and the biodistribution and image quality of the radiolabeled antibody was evaluated. Radiolabeling was achieved in a solid-phase system consisting of 1,3,4,6-tetrachloro-3a,6a-diphenylglycoluril. Labeling efficiencies and protein purification were accomplished using gel exclusion chromatography while radioimmunoreactivity was determined using a solid-phase radioimmunoassay procedure. The biodistribution of I-131-labeled MAbs was determined in Sprague-Dawley rats up to 7 days after injection. Highest organ concentrations were observed in liver (3.91 +/- 0.47 (SD) and 0.17 +/- 0.04 (SD) mean percent injected dose at 1-7 days after injections) and in thyroid (5.33 +/- 0.71 (SD) and 5.32 +/- 2.01 (SD) mean percent injected dose at 1-7 days after injection). Nude mice, bearing either a small cell lung tumor (NCI-H69) or a nonspecific tumor (adenocarcinoma), were injected with 400-800 microCi of I-131 labeled monoclonal antibody. Optimum tumor visualization was observed 2-4 days after injection with tumor concentrations as high as 10.4% of the initial injected dose. The results demonstrated that radioimmunoimaging of human small cell lung carcinoma was feasible with the tumor-specific IgM I-131-labeled MAb.

Adenocarcinoma↗

Manganese-52m, a new short-lived, generator-produced radionuclide: a potential tracer for positron tomography.

A new generator system has been developed using the Fe-52 leads to Mn-52m parent-daughter pair. Fe-52, half-life 8.3 hr, is isolated on an anion-exchange column, and Mn-52m is eluted in hydrochloric acid. Breakthrough is less than 0.01% and the yield is 75%. The 21.1-min half life of Mn-52m is ideal for use in sequential studies, but is long enough to permit radiochemical manipulations to control biodistribution. Animal studies indicate that Mn-52m is an ideal nuclide for myocardial imaging, combining rapid blood clearance and high concentration in the myocardium. An added advantage is that Mn-52m decays 98% by positron emission and is useful for positron computer tomography.

Animals↗

Cardiac blood pool imaging over the complete cardiac cycle with a multiformat imager.

A new method of obtaining scintigraphic images of the cardiac blood pool for the study of ventricular wall motion is described. The method, which is based upon an inexpensive modification of a commercial multiformat imaging device, yields a set of serial gated images covering the entire cardiac cycle. These images may be converted into a film loop to yield a continuous motion picture of the mechanical cycle of the heart.

Heart Function Tests↗

Assay of 32P-sodium phosphate using a commercial dose calibrator.

Dose calibrators are not usually used to measure the activity of pure beta-emitting radionuclides. In this work, the activity of 32P-sodium phosphate was accurately measured with a Capintec CRC-2 dose calibrator. Using a calibration knob setting of 012 on the 1-mCi range, the 32P dose (in mCi) could be calculated directly simply by multiplying the instrument readout by 10. The dose calibrator response was found to be linear at this knob setting and moderate alterations in geometry produced no significant changes.

Phosphorus Radioisotopes↗

The allotransplantation of partial joints in the treatment of osteoarthritis of the knee.

Nine allografts replacing part of the knee have been carried out in 8 patients. In all patients the graft was incorporated without clinical evidence of rejection. In one case a low grade infection was brought under control without surgery and thus far has not impaired the results. All patients have a good functional range of movement and the alignment of the knee has been maintained by the grafts which display little or no collapse at all. Histological evidence in one case revealed cartilage viability at 14 months. Two years interim observations are encouraging enough to continue on with this technique in the knee with disease severe enough not to be helped by osteotomy but not so diffusely damaged as to require total knee arthroplasty.

Aged↗