Professor, Department of Radiology (Nuclear Medicine)
Professor, Department of Microbiology & Immunology
Sylvia and Robert S. Olnick Faculty Scholar in Cancer Research
Molecular nuclear medicine plays an important role in the diagnosis and therapy of cancer and infectious diseases. Molecular nuclear medicine agents are compounds which are labeled with radioisotopes. Depending on the properties of a radioisotope, such compounds can be used for diagnostic or therapeutic purposes or both. For example, radioimmunotherapy takes advantage of the specificity of the antibody-antigen interaction to deliver a radioisotope which emits microbicidal radiation to a target, either a cancer cell or a microbe.
Radioimmunotherapy is currently used successfully for the treatment of non-Hodgkin lymphoma in patients who failed all other treatments. We are interested in applying radioimmunotherapy to treatment of metastatic melanoma - one of the few cancers with the increasing incidence for which there is no effective cure once it spreads. This project is already in the clinic with Phase I/II trial on-going in Hadassah, Israel. Another novel application of radioimmunotherapy which has been discovered in our laboratory is treatment of infectious diseases. This is important because of the urgent need for new approaches to treat infectious diseases caused by the increasing prevalence of highly resistant microorganisms and by occurrence of many infections in immunosuppressed individuals in whom standard antimicrobial therapy is not effective. In addition, the HIV epidemic is now 30 years old and there are still no vaccine and no cure. We are developing a treatment strategy for HIV both systemically and in the central nervous system by targeting gp41 viral antigen expressed on the surface of the host HIV-infected cells. This project is being supported by the Bill and Melinda Gates Foundation. Yet another novel application of targeted therapy which our laboratory is interested in is radioimmunotherapy of viral cancers such as HPV-related cervical and head and neck cancers and hepatitis B-related liver cancer. By targeting radiolabeled antibodies to viral antigens which cancer cells continue to express – we are hoping to achieve exquisite specificity and low toxicity of treatment.
As we are a radiation therapy lab, we are also thinking how to protect the healthy tissues in patients undergoing radiation therapy from harmful radiation side effects. We have discovered that a naturally occuring pigment melanin is capable of dissipating incoming radiation photons and catching damaging free radicals thus minimizing the radiation damage. We are developing melanin based radioprotectors such as melanin nanoparticles for bone marrow protection and melanin-containing foods for protection of the gastrointestinal tract.
Jandl T, Revskaya E, Jiang Z, Harris M, Dorokhova O, Tsukrov D, Casadevall A, Dadachova E. Melanoma stem cells in experimental melanoma are killed by radioimmunotherapy. Nucl Med Biol. 2012 Nov 9. E pub ahead of print
E. Revskaya, P.Chu, R.C. Howell, A.D. Schweitzer, R.A. Bryan, M. Harris, G. Gerfen, Z.Jiang, T. Jandl, K.Kim, L-M. Ting, R.S. Sellers, A. Casadevall, E. Dadachova Compton scattering by internal shields based on melanin-containing mushrooms provides protection of gastrointestinal tract from ionizing radiation. Cancer Biother. Radiopharm. 27(9):570-6 (2012).
Dufresne SF, Datta K, Li X, Dadachova E, Staab JF, Patterson TF, Feldmesser M, Marr KA. Detection of Urinary Excreted Fungal Galactomannan-like Antigens for Diagnosis of Invasive Aspergillosis. PLoS ONE 7(8):e42736 (2012).
R.A. Bryan, A.J. Guimaraes, S. Hopcraft, Z. Jiang, K. Bonilla, A. Morgenstern, F. Bruchertseifer, M. Del Poeta, A.Torosantucci, A. Cassone, J.D. Nosanchuk, A. Casadevall, and E. Dadachova Towards developing a universal treatment for fungal disease using radioimmunotherapy targeting common fungal antigens. Mycopathologia 73(5): 463-471 (2012)
Z. Jiang, R. A. Bryan, A. Morgenstern, F. Bruchertseifer, A. Casadevall and E. Dadachova Treatment of early and established Cryptococcus neoformans infection with radiolabeled antibodies in immunocompetent mice. Antimicrob. Agents Chemother. 56(1):552-4 (2012)
E. Dadachova, S.G. Kitchen, G. Bristol, G.C. Baldwin,E. Revskaya, C. Empig, G.B. Thornton, M. K. Gorny, S. Zolla-Pazner, A. Casadevall Pre-clinical evaluation of a 213Bi-labeled 2556 antibody to HIV-1 gp41 glycoprotein in HIV1 mouse models as a reagent for HIV eradication. PLOS ONE 7(3): e31866 (2012).
S. Jaini and E. Dadachova 18FDG for Therapy of Metabolically Active Tumors. Sem. Nucl. Med. 42(3):185-9 (2012).
Nosanchuk JD, Dadachova E. Radioimmunotherapy of fungal diseases: the therapeutic potential of cytocidal radiation delivered by antibody targeting fungal cell surface antigens. Front Microbiol. 2:283 (2012)
Dadachova E, Casadevall A. Cryptococcus neoformans as a Model for Radio-immunotherapy of Infections. Interdiscip Perspect Infect Dis. 830286 (2011)
M. Harris, X-G. Wang, Z. Jiang, G. L. Goldberg, A. Casadevall, and E. Dadachova Radioimmunotherapy of experimental head and neck squamous cell carcinoma (HNSCC) with E6-specific antibody using a novel HPV-16 positive HNSCC cell line. Head Neck Oncol. 3(1):9 (2011).
A. P. Johnson, L. M. Pratt, T. A. Vishnivetskaya, S. Pfiffner, R. A Bryan, E. Dadachova, L. Whyte, K. Radke, E. Chan, S. Tronick, G. Borgonie, R. L. Mancinelli, L. J. Rothschild, D. A. Rogoff, D. D. Horikawa, T. C. Onstott Extended Survival of Several Organisms and Amino Acids under Simulated Martian Surface Conditions. Icarus 211(2):1162-1178 (2011).
Turick CE, Ekechukwu AA, Milliken CE, Casadevall A, Dadachova E. Gamma radiation interacts with melanin to alter its oxidation-reduction potential and results in electric current production. Bioelectrochemistry. 82(1):69-73 (2011).
A. Khajo, R.A. Bryan, Y. Levitsky, M. Friedman, R. Burger, A. Casadevall, R. Magliozzo and E. Dadachova Protection of melanized Cryptococcus neoformans from lethal dose gamma irradiation involves changes in melanin's chemical structure and paramagnetism. PLOS ONE 6(9): e25092 (2011).
R. A. Bryan, Z. Jiang, M. Friedman, andE. DadachovaThe effects of gamma radiation, UV and visible light on ATP levels in yeast cells depend on cellular melanization. Fungal Biol. 115(10): 945-949 (2011).
B. Ballard, Z. Jiang, C. E. Soll, E. Revskaya, C. S. Cutler, E. Dadachova, L. C. FrancesconiIn vitro and in vivo evaluation of melanin-binding decapeptide 4B4 radiolabeled with 177Lu, 166Ho and 153Sm radiolanthanides for the purpose of targeted radionuclide therapy of melanoma. Cancer Biother. Radiopharm. 26(5): 547-556 (2011).
M. Paroder-Belenitsky, M. J. Maestas, O. Dohán, J. P. Nicola, A. Reyna-Neyra, A. Follenzi, E. Dadachova, S. Eskandari, L. M. Amzel, N. Carrasco Mechanism of Anion Selectivity and Stoichiometry of the Na+/I- Symporter (NIS). PNAS 108(44):17933-8 (2011)
C.A. Saylor, E. Dadachova, A. Casadevall Murine IgG1 and IgG3 isotype switch variants promote phagocytosis of Cryptococcus neoformans through different receptors. J. Immunol. 184:336-343 (2010).
R. Phaeton, X.G. Wang, M. H. Einstein, G. L. Goldberg, A. Casadevall, and E. Dadachova The influence of proteasome inhibitor MG132, external radiation and unlabeled antibody on the tumor uptake and biodistribution of 188Re-labeled anti-E6 C1P5 antibody in cervical cancer in mice. Cancer 116(S4):1067-1074 (2010).
Winterroth L, Rivera J, Nakouzi AS, Dadachova E, Casadevall A. A neutralizing monoclonal antibody to edema toxin and its effect on murine anthrax.Infect Immun. 78(6):2890-8 (2010).
A. D. Schweitzer, E. Revskaya, P. Chu, V. Pazo, M. Friedman, J.D. Nosanchuk, S. Cahill, S. Frases, A. Casadevall, and E. Dadachova Melanin-covered nanoparticles for protection of bone marrow during radiation therapy of cancer. Intern. J. Rad. Oncol. Biol. Physics. 78(5):1494-502 (2010).
R. A. Bryan, Z. Jiang, R. C. Howell, A. Morgenstern, F. Bruchertseifer, A. Casadevall, and E. Dadachova Radioimmunotherapy is More Effective than Antifungal Treatment in Experimental Cryptococcal Infection. J. Infect. Dis. 202(4): 633-7 (2010)
R. Phaeton, M. Harris, Z. Jiang, X-G. Wang, M. H. Einstein, G. L. Goldberg, A. Casadevall, and E. Dadachova Radioimmunotherapy with antibody to HPV-16 E6 oncoprotein is effective in experimental cervical tumor expressing low levels of E6. Cancer Biol. Ther. 10(10): 1041-1047 (2010).
E. Dadachova Therapy of cancer with alpha-emitters labeled peptides. Semin. Nucl. Med. 40:204-208 (2010).
More Information About Dr. Ekaterina Dadachova
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Montefiore Medical Park
1695A Eastchester Road , Room 103
Bronx, NY 10461
NBC News features Dr. Ekaterina Dadachova and her focus on radioimmunotherapy. Preclinical research shows it has the potential to eradicate HIV.
Science features new research by Drs. Claudia Gravekamp and Ekaterina Dadachova that uses radioactive bacteria to destroy metastatic pancreatic cancer.