Academic literature on the topic 'Radioisotopes in hematology'

Abstract Radioisotope Synovectomy (RS) is defined as the intra-articular injection of radioisotopic agents with the aim of fibrosis on hypertrophic synovium in the target joint for hemophilia. Yttrium90 (Y90) and Rhenium186 (Re186) are approved isotopes in Europe. The only radioisotope which approved in the USA for RS is Phosphorus 32 (P32). We have successfully used Y90 and Re186 for 8 years in target joints of hemophiliac patients. For the last 30 years, no malignant transformation has been reported in hemophilia with RS. However, recently, development of acute lymphoblastic leukemia in two hemophiliac children after RS has been reported in the USA. Even though P32 was the responsible radioisotopic agent, safety concerns have arisen due to exposure to all type of radioisotopic agents which may cause chromosomal breakages (CBs) and oncological transformation. The aim of this prospective and Ethics commitee-approved study was to investigate the early genotoxic effect on peripheral blood lymphocytes induced by Y90 and Re186 in children who underwent RS for chronical synovitis. All patients and parents were informed according to Helsinki Decleration. Thirty-three patients with persistent synovitis (23 hemophilia-A, 9 hemophilia-B,1 FVII deficiency) were enrolled to the study. All patients were male except one case. The mean age was 16.4 ±6.2 years (range:8–40). RS was performed as an outpatient procedure by using Y90 for knees (n=9)(5 mCi) and Re186 for elbows and ankles (n=14)(2 mCi)(CIS Bio International/Gif-sur-Yvett Cedex-France). In 6 patients, both agents were used simultaneously in one session. No radioisotope leakage away from the injection site was observed during and after procedure. Heparinised peripheral blood samples were obtained for lymphocyte cultures from all patients at three different time points (prior to RS, after 3 days and after 90 days). Diepoxybutane (DEB) test was used for the evaluation of chromosomal breakages in patients by culturing their blood along with blood from a sex-matched control with a working solution of 11 ug/ml. Five μl pure DEB was added to 5 ml of sterile dH2O. Afterwards, 10 μl of the first solution was added to 1 ml of sterile dH2O. This is the working solution at 11 ug/ml. A total of 50 metaphases from each culture were examined and scored according to the procedure. All cytogenetic analysis were performed in the Medical Genetics Laboratory of Ege University Hospital. Due to technical problems, parameters of 29 patients were evaluated. Chromosomal breakages (CB) were found in 20 patients prior to treatment. We have found CBs in 4 additional patients after 3 days of RS. However, all these CBs were disappeared 90 days after. CBs were found to be persisted in 17 patients. Mean frequency of CBs was (0.0707±0.0829/1000 cells) and was not significantly increased after 3 days (0.0828±0.0747) but significantly decreased at 90 days (0.0379±0.0456). The difference of the results of two radioisotopes were not significant. In conclusion, although RS with Y90 and Re186 does not seem to induce the genotoxic effects significantly on peripheral blood lymphocytes in hemophilic children, the significant decrease in the number of CBs between the 3rd and 90th days may be accepted as a warning for the requirement of risk/benefit ratios which should be taken into account for any individual patient. Therefore medical treatment in hemophilia for synovitis should be suggested before RS and families should be informed properly.

Background: The introduction of monoclonal antibodies, either as native molecules or conjugated to radioisotopes or other toxins, has led to new therapeutic options for patients with hematologic malignancies. In addition, the use of small molecules against specific cell surface receptors, enzymes, and proteins has become an important strategy in the treatment of such disorders. Methods: The author reviewed the published clinical trials of monoclonal antibody and other targeted therapies in hematologic malignancies. Results: Results from several trials demonstrate a therapeutic benefit for the use of monoclonal antibodies (either native or conjugated) and other targeted therapies, used alone or in combination with standard cytotoxic chemotherapy. Conclusions: Targeted therapy of hematologic malignancies seems to be an effective and less toxic approach to the treatment of such disorders. Nevertheless, additional studies are needed to determine where and when such management fits into a therapeutic regimen for any given disorder, whether upfront or as salvage therapy, alone or in combination with chemotherapy (concurrent or sequential).

Abstract Background: Viral vectors based on the Edmonston strain of measles virus (MV-Edm) selectively destroy all tumor cell lines tested in vitro. The oncolytic activity of the virus is enhanced by expression of the thyroidal sodium iodide symporter (MV-NIS) that allows selective 131I uptake by infected tumor cells and eliminates myeloma tumor xenografts that are resistant to the parent virus. MV-NIS is being considered for therapy of patients with relapsed or refractory multiple myeloma. Advanced myeloma is associated with significant immunosuppression with the potential risk of uncontrolled virus proliferation. The number of agents with activity against MV is limited. Low energy (Auger) electrons have a short path length and selectively damage cells in which the isotope decays. Thus, we hypothesized that the Auger electron emitting isotope 125I, selectively taken up by cells expressing NIS, can be used to control viral proliferation. Methods: A replication competent MV that expressed both a soluble form of carcinoembryonic antigen (CEA) and NIS (MV-NICE) was rescued and characterized. Cells were infected with MV-NICE or control vectors and exposed to 125I with appropriate controls. CEA expression and viral titers were determined at different time points. The role of free radical generation on virus replication was explored. In vivo control of MV-NICE replication with 125I was attempted. Results: MV-NICE replication in vitro is inhibited by the selective uptake of 125I by cells expressing NIS. Extracellular decay of the isotope has no effect on virus proliferation. Auger electron damage is in part mediated by free radicals and abrogated by glutathione. In myeloma xenografts, control of MV-NICE with 125I was not possible under the conditions of the experiment. Conclusion: MV-NICE does not replicate faster in the presence of radiation under our experimental conditions. Auger electron emitting isotopes effectively stop propagation of MV vectors expressing NIS in vitro. Additional work is necessary to translate these observations in vivo.

AbstractMonoclonal antibody therapy with rituximab in combination with standard chemotherapy has improved the survival of patients with advanced-stage follicular lymphoma (FL). A series of next-generation anti-CD20 antibodies may be less immunogenic and have even greater antitumor activity through augmented interactions with host effector mechanisms responsible for tumor cell kill. Additional approaches with patient-specific immunoglobulin idiotype vaccines; novel monoclonal antibodies binding to biologically active cell-surface antigen are also demonstrating early clinical activity. Antibodies targeting radioisotopes, toxins or drugs are also slowly entering clinical trials and practice. Last, allogeneic stem cell transplantation following reduced-intensity conditioning provides graft-versus-tumor immune responses that may be able to control FL and allow this risky but potentially curative treatment option to older patents or those with comorbidities.

Cancer is second only to trauma as a cause of death in children, accounting for approximately 10% of all childhood deaths. The application of radioisotopes in the treatment of malignant diseases in children consists of detecting and estimating the degree of tumour spread by application of tumour-specific and non-specific radiopharmaceuticals, as well as the treatment of some malignant diseases. Paramount to any successful nuclear medicine examination is the establishment of acquisition protocols that allow high quality images to be obtained while ALARA principles are followed. Pediatric-specific issues should be anticipated and addressed in the planning of the studies to maximize the utility of the technique in this challenging group of patients, so the goal of this article is to summarize general prerequisites for the application of nuclear medicine diagnostic procedures in pediatric oncology patients.

SummaryAn enzyme-linked immunosorbent assay (ELISA) for the measurement of human tissue-type plasminogen activator (t-PA) was developed. Microtiter plates were coated with a mixture of two monoclonal antibodies and bound t-PA was quantitated with a third monoclonal antibody linked to peroxidase. The lower limit of sensitivity of the assay was 0.2 ng of t-PA per ml. The concentration of antigen in citrated plasma of human subjects was found to be 3.4 ± 0.8 ng/ml. The assay had a good reproducibility with values of 3.8, 6.5 and 4.9 percent respectively for the intra-, inter-assay and inter-dilution variation coefficients. The results of the ELISA assay on plasma samples from patients during thrombolytic therapy with t-PA correlated very well, over a wide concentration range, with those obtained with a previously described two-site immuno-radiometric assay (r = 0.96). This ELISA with monoclonal antibodies constitutes a stable and reproducible set of reagents for the measurement of t-PA antigen in biological fluids, avoiding the disadvantages of the use of radioisotopes and of polyclonal antibodies.