Ekaterina Dadachova

..The study of breast cancer patients suggests that the tumor and normal organ dosimetry of 18F-FDG makes it suitable for therapy of this malignancy...

....

..The usefulness of radioimmunotherapy (RIT) for infectious diseases was recently demonstrated for several fungal and bacterial infections, but the mechanisms by which RIT is effective against microbes are uncertain...

..These results indicate that radiolabeled melanin-binding peptides are efficient and safe in treatment of melanoma and could be potentially useful against this tumor...

..However, considerable basic work remains to be done to ascertain the optimal conditions for the efficacy of RIT for infection...

..The aim of this proof-of-principle study was to demonstrate the efficacy of a therapeutic strategy of targeting and eliminating HIV-1-infected cells with radiolabeled antibodies specific to viral proteins in vitro and in vivo...

..RIT reduced mortality in high-burden infections, and we found no evidence for the development of radiation-resistant cells...

..Overall, we are hopeful that targeted radionuclide therapy of metastatic melanoma will become a reality within the next few years...

..We hypothesized that ionizing radiation could change the electronic properties of melanin and might enhance the growth of melanized microorganisms...

..RIT of VAC is fundamentally different from the previously described uses of RIT, which have targeted tumor-associated antigens that are "self" proteins...

....

..The availability of such antibodies would eliminate the necessity of having antibodies specific for each particular microorganism and would enormously enhance the development of RIT of infectious diseases...

..Melanin protected fungi against ionizing radiation and its radioprotective properties were a function of its chemical composition, free radical quenching, and spherical spatial arrangement...

..Here we carried out pre-clinical development of (188)Re-6D2 to accrue information necessary for a Phase I trial in patients with metastatic melanoma...

....

..The authors are optimistic that therapeutic agents targeting melanin to deliver radionuclide therapy could appear in the clinic within a decade...

....

..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...

..Dadachova and Casadevall anticipate that RIT can be developed for many types of infectious diseases, including microbes resistant to conventional antimicrobial therapy and agents of biological warfare...

....

..This review highlights the use of armed antibodies to target infected host cells or to target the microbes themselves, describing challenges and future directions for both approaches...

..01). The treatment did not cause hematological toxicity, as demonstrated by platelet counts. This feasibility study establishes that RIT can be applied to the treatment of bacterial infections...

..We conclude that RIT is more effective than amphotericin B against systemic infection with C. neoformans...

..The results point to the independence of RIT of the immune status of the host, which is encouraging for translation of this strategy into the clinic...

....

....

..Melanin, a high-molecular weight pigment that is ubiquitous in nature, protects melanized microorganisms against high doses of ionizing radiation. However, the physics of melanin interaction with ionizing radiation is unknown...

..Thus, these heptapeptides appear to have potentially significant advantages for targeted therapy of melanoma relative to existing melanin-binding peptides...

....

..In conclusion, RIT of metastatic melanoma can be effective over a wide range of tumor melanin concentrations. The results can be useful in the design of a clinical trial of melanin-targeting RIT in patients with metastatic melanoma...

..Based on our earlier proof-of-principle results targeting HIV-1 infected cells with radiolabeled antibody (mAb) to gp41 viral antigen, we embarked on identifying a suitable candidate mAb for preclinical development...

..We report the results of a therapy study with (131)I(-) and (188)ReO(4)(-) of breast cancer in polyoma middle T oncoprotein (PyMT) transgenic mice endogenously expressing the Na(+)/I(-) symporter (NIS)...

..anthracis Sterne spores. These results indicate that RIT with MAbs that target B. anthracis toxin components can be used to treat experimental anthrax infection and suggest that toxigenic bacteria may be targeted with radiolabeled MAbs...

..These results are important for the development of positherapy with (18)F-FDG for refractory metastatic breast and other cancers...

..However, that study opened the question whether radioimmunotherapy can suppress the growth of cervical tumors with low E6 and E7 expression, such as may be seen in patients...

..There is an urgent need to find new approaches to treatment and prevention of virus-associated cancers...

..We aimed at extending this approach to HPV-related head and neck cancer by performing radioimmunotherapy (RIT) targeting E6 and E7 oncogenes with radiolabeled mAbs...

..However, MAb 7.5G slowed the proteolytic digestion of PA by furin in vitro, suggesting a potential mechanism for Ab-mediated protection. These observations indicate that some Abs to domain 1 can contribute to host protection...

..We conclude that a specific receptor for IgG3 exists in mice that is structurally different from the known FcgammaRs...

..They hypothesized that the pretreatment of tumor cells with various agents that cause cell death and/or elevation of E6 levels would increase the accumulation of radiolabeled antibodies to E6 in cervical tumors...

..The ability of melanin-containing mushrooms to provide remarkable protection against radiation suggests that they could be developed into oral radioprotectors...

....

..neoformans is heterogeneous in its spatial distribution and changes with age. Furthermore, our results suggest several mechanisms by which the capsule may protect the fungal cell against exogenous environmental factors...

..neoformans in different substrates affected cell and capsule size but not capsule induction. Hence, the type of pigment produced by C. neoformans is dependent on the substrate and not all pigments meet the criteria for melanins...

..Our results show that melanin in C. neoformans cells is susceptible to some damage by hydroxyl radical formed in lethal radioactive aqueous environments and serves a protective role in melanized fungi that involves sacrificial breakdown...

....

..This approach was recently shown to target and eliminate HIV-1-infected cells in vitro and in mouse models, and provides a new approach for eliminating virally infected cells...

..HGA melanization was laccase dependent and repressed by high concentrations of glucose. The ability of C. neoformans to utilize a bacterial melanin precursor compound suggests a new substrate source for melanization in the environment...

..This observation provides a precedent that could explain the source of a substrate for C. neoformans melanization in the environment...

..These observations will help to improve the treatment protocols of radioimmunotherapy, as well as immunotherapy...

..Here we investigated the interaction of MSC with RIT as a possible mechanism for RIT efficacy...

..Cell wall pigmentation in W. dermatitidis depends on the WdPKS1 gene, which encodes a polyketide synthase required for generating the key precursor for dihydroxynaphthalene melanin biosynthesis...

..Hence, there is cautious optimism that the years ahead will see more mAbs in clinical use against microbial diseases...

..In contrast, in non-melanized cells visible light led to increase in ATP levels; gamma radiation did not cause any changes while UV exposure resulted in some ATP decrease, however, much less pronounced than in melanized cells...

..Our results indicate that C. neoformans capsular enlargement also occurs by apical growth and that budding results in capsular rearrangements...

....

....

..Also, recent developments in targeted PET imaging could increase the range of PET pharmaceuticals potentially useful for positron therapy of metastatic cancers because of increased specificity of these tracers in comparison with FDG...

....

....

..In addition, the creation of "panantibodies" for RIT which would recognize antigens shared by the whole class of pathogens such as fungi, for example, would facilitate the introduction of RIT into the clinic...

..As further validation of the use of 213Bi-HuCC49DeltaCH2 for RIT, a study using 131I was conducted. The overall survival of mice receiving 213Bi-HuCC49DeltaCH2 was greater than those that received 131I-HuCC49DeltaCH2...

..In this study, we endeavored to characterize the biologic behavior of perrhenate, especially in relation to iodide and pertechnetate, to better explore its possible therapeutic role...

..The maximum tolerated dose was also dependent on the tumor xenograft model used. These studies indicate that genetically engineered antitumor diabody molecules can be used as effective vehicles for radioimmunotherapy...

..Based on these in vitro and in vivo studies, the CHX-A" DTPA ligand should be considered a suitable bifunctional chelate for the radiolabeling of monoclonal antibodies with 177Lu for radioimmunotherapy applications...

..We found that gamma, beta, and alpha radiation affected cells through different pathways...

..These results have implications for the development of new antibody-based therapies...

..The long-term goal of this research is to contribute to the development of a novel cost-effective radionuclide therapy for treatment of breast cancer and, possibly, for other NIS-expressing cancers such as thyroid cancer. ..

..It will also provide some understanding of the fundamentals of interactions between microorganisms and antibodies radiolabeled with particulate-emitting radioisotopes in vitro and in vivo. ..

..Such knowledge will contribute to development of a novel therapeutic modality based on radioimmunotherapy for treatment of currently incurable or multidrug-resistant AIDS-associated opportunistic infections. ..

..Such knowledge will contribute to development of a novel therapeutic modality based on radioimmunotherapy for treatment of currently incurable or multidrug-resistant AIDS-associated opportunistic infections. ..

..Such knowledge will contribute to development of a novel therapeutic modality based on radioimmunotherapy for treatment of currently incurable or multidrug-resistant AIDS-associated opportunistic infections. ..