{"id":950,"date":"2025-06-15T18:15:14","date_gmt":"2025-06-15T18:15:14","guid":{"rendered":"http:\/\/littleheroesfoundation.org\/?p=950"},"modified":"2025-06-15T18:15:14","modified_gmt":"2025-06-15T18:15:14","slug":"in-the188re-group-40-and-20-of-mice-were-alive-after-treatment-with-100-p-0","status":"publish","type":"post","link":"https:\/\/littleheroesfoundation.org\/?p=950","title":{"rendered":"\ufeffIn the188Re group, 40% and 20% of mice were alive after treatment with 100 (P< 0"},"content":{"rendered":"

\ufeffIn the188Re group, 40% and 20% of mice were alive after treatment with 100 (P< 0.005) and 50 Ci (P< 0.05) of188Re-18B7, respectively. reduced their organ fungal burden, and significantly prolonged their survival without apparent toxicity. This study establishes the principle that targeted radiation can be used for the therapy of an infectious disease, and suggests that it may have wide applicability as an antimicrobial strategy. Radiation possesses microbicidal properties and -irradiation is routinely used for the sterilization of medical supplies and certain foods. Ionizing radiation such as -rays, -particles, and especially -particles from external sources can kill different strains of bacteria and fungi such asEscherichia coli, Cryptococcus neoformans(CN), andMycobacterium tuberculosis(13). Despite its microbicidal properties, radiation is not used in current antimicrobial therapy. Dadachova (4) recently proposed using therapeutic radionuclides for the treatment of multidrug-resistant infections. However, to realize the full benefits of ionizing radiation as an anti-infective treatment, it is important that the radiation be specifically SB 203580 hydrochloride targeted to the sites of infection to minimize toxicity to the host. Evidence that radiation can be targeted to a focus of infection by specific antibody comes from the observation that radiolabeled antibodies can be used to visualize the sites of infection in patients withPneumocystis cariniipneumonia (5) and tuberculomas in rabbits infected withMycobacterium bovis(bacillus CalmetteGurin) (6). The use of antibodies to granulocytes for imaging the sites of infection in patients has also been reported (7). The fact that radiolabeled antibodies can detect foci of infectionin vivo(5,6) implies that antigenantibody interactions can be used to deliver radionuclides to microorganismsin vivo. Hence, the next logical step in developing radiotherapy for infectious diseases would be to ascertain whether particulate radiation could be targeted to kill microorganisms in the infectious foci by specific radiolabeled antibodies. This option is potentially very attractive as an antifungal strategy, because fungal cells in tissue are relatively large targets with dimensions that approximate the size of host cells. Furthermore, in contrast to tumor cells, yeast cells are antigenically very different from host tissue, and thus provide the potential for abundant antigenantibody interactions with the fungal cell and low crossreaction with the host tissue. Targeting fungi with radioimmunotherapy (RIT) makes sense, because fungal diseases are notoriously difficult to treat and currently constitute a major clinical problem (8). Despite its theoretical promise, we are not aware of attempts to explore the potential usefulness of RIT against infectious diseases. In this study, we explored the potential efficacy of RIT against an experimental fungal infection by using CN. CN is a major fungal pathogen that causes life-threatening meningoencephalitis in 68% of patients with AIDS. Cryptococcal infections in immunocompromised patients are often incurable, because antifungal drugs do not eradicate the infection in the setting of severe immune dysfunction (9,10). CN provides a good system to study the potential usefulness of RIT, because there are excellent mouse models available, well characterized mAbs to CN antigens exist, and immunotherapy of CN infection with passive antibody (11) is already in clinical evaluation. Two radioisotopes SB 203580 hydrochloride were evaluated in this study: a high-energy -emitter Rhenium-188 (188Re) and an -particle emitter Bismuth-213 (213Bi).188Re (t[1\/2]= 16.9 h) (Emax= 2.12 MeV) has recently emerged as an attractive therapeutic radionuclide for cancer radioimmunotherapy, palliation of skeletal bone pain, and endovascular brachytherapy to prevent restenosis after angioplasty (1214).213Bi (t[1\/2]= 45.6 min) emits SB 203580 hydrochloride a high linear energy transfer -particle withE= 5.9 MeV with a path length in tissue of 5080 m. Theoretically, a cell can be killed with one or two -particle hits.213Bi was proposed for use in single-cell disorders and some solid cancers (1518), and has been used to treat patients with leukemia in Phase I clinical trials (19,20). == Methods == CN.American Type Culture Collection strain 24067 (serotype D) was used in all experiments. It was grown in Sabouraud dextrose broth (Difco) for 24 h at 30C with constant shaking. Organisms were centrifuged three times with PBS, pH 7.2, at 200 g. Antibodies and Immunoreactivity Determination.MAb 18B7 (IgG1) was produced as described (21). MAb MOPC21 (ICN Biomedicals, Aurora, OH) was used as an irrelevant isotype-matched control mAb in therapy experiments. The immunoreactivity of 18B7 mAb radiolabeled with111In or99mTc was determined by ELISA as described in ref.22. Experiments were performed in triplicate. Conjugation of Bifunctional Chelate SCN-CHXAto Antibodies.mAbs 18B7 and MOPC21 were conjugated toN-[2-amino-3-(p-isothiocyanatophenyl)propy1]-trans-cyclohexane-1,2-diamine-N, N,N,N,N-pentaacetic acid (CHXA) as in ref.23, with an average number of chelates per antibody ranging from 0.7 to 3.0 as determined by the yttrium-arsenazo SB 203580 hydrochloride<\/a> III spectrophotometric method (24). Radioisotopes.Na99mTcO4was purchased from Syncor (Bronx, NY);111InC13was purchased from Iso-Tex Diagnostics, Mouse monoclonal to CD29.4As216 reacts with 130 kDa integrin b1, which has a broad tissue distribution. It is expressed on lympnocytes, monocytes and weakly on granulovytes, but not on erythrocytes. On T cells, CD29 is more highly expressed on memory cells than naive cells. Integrin chain b asociated with integrin a subunits 1-6 ( CD49a-f) to form CD49\/CD29 heterodimers that are involved in cell-cell and cell-matrix adhesion.It has been reported that CD29 is a critical molecule for embryogenesis and development. It also essential to the differentiation of hematopoietic stem cells and associated with tumor progression and metastasis.This clone is cross reactive with non-human primate<\/a> Friends-wood, TX;188Re in the form of Na perrhenate Na188ReO4was eluted from a188W\/188Re generator (Oak Ridge National Laboratory, Oak Ridge, TN); and Actinium-225 (225Ac) for construction of.<\/p>\n","protected":false},"excerpt":{"rendered":"

\ufeffIn the188Re group, 40% and 20% of mice were alive after treatment with 100 (P< 0.005) and 50 Ci (P< 0.05) of188Re-18B7, respectively. reduced their organ fungal burden, and significantly prolonged their survival without apparent toxicity. This study … \n\n

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