Eszter Boros, PhD

Assistant Professor (September 1, 2017 -) Department of Chemistry (co-appointed with Departments of Pharmacology and Radiology) Stony Brook University 100 Nicolls Road, Stony Brook, NY 11790, USA

Education & Harvard Medical School/ Massachusetts General Hospital Charlestown, MA, USA Positions held Instructor in Radiology, Assistant in Chemistry. Athinoula A. Martinos Center for Biomedical Imaging. Research focus on multimodal imaging probes (PET/fluorescence) for pulmonary fibrosis and breast cancer. (Aug 2015 – Aug 2017)

Harvard Medical School/ Massachusetts General Hospital Charlestown, MA, USA Postdoctoral fellow, Department of Radiology. Athinoula A. Martinos Center for Biomedical Imaging. Research focus on single amino acid Gadolinium MRI probes. (Nov 2011 – July 2015)

University of British Columbia Vancouver, BC, Canada PhD, Department of Chemistry, November 2011. Research focus on acyclic chelates for the radioactive imaging with radiometals. (Sept 2007 – Nov 2011)

University of Zurich Zurich, ZH, Switzerland MSc, Department of Chemistry, August 2007. Design and synthesis of bifunctional [2+1] Re/Tc complexes for nuclear targeting of cells with auger-emitters. (Aug 2006 – Aug 2007)

Awards Alfred Werner Fellowship, University of Zurich (2005/2006/2008), University of British Columbia Graduate Scholarship (2009-2011), First Place Travel Award ACS Division of Nuclear Chemistry and Technology (2010), Swiss National Science Foundation early postdoc mobility grant (2011-2013), Outstanding Poster Award Metals in Medicine Gordon Research Conference (2012), Student Travel Stipend Award of the World Molecular Imaging Congress (2013), Swiss National Science Foundation advanced postdoc mobility grant (2013-2014), SNMMI Future Leaders Academy (2015), K99 NHLBI Pathway to Independence Award (2015-2017), First place Young Investigator Award, SNMMI (Radiopharmaceutical Science Council) (2017), Top Oral Presentation EuroBIC14 (2018), “One to watch” 2019 (SNMMI), Young Academic Inventor’s Award 2019 (SBU Chapter of The National Academy of Inventors).

Research Experience Harvard Medical School/ Massachusetts General Hospital (Radiology, Postdoc) Advisor: Peter Caravan Explored the synthesis of a single amino acid gadolinium chelate as a tool for targeted high-relaxivity MRI contrast agents and PET-fluorescence multimodal imaging probes for fibrosis and breast cancer imaging. Work involved organic synthesis, inorganic chemistry, analytical chemistry, radiochemistry, polyacrylamide gel electrophoresis, solid-phase peptide synthesis, cell culture, small animal surgery, small animal imaging with preclinical PET/CT and MRI scanners.

University of British Columbia (Chemistry, PhD) Advisors: Chris Orvig, Michael J. Adam Developed acylic chelators for the stable complexation and imaging with radiometals. Work involved organic synthesis, inorganic chemistry, analytical chemistry, radiochemistry, NMR spectroscopy, HPLC, column chromatography.

University of Zurich (Chemistry, BSc, MSc) Advisor: Roger Alberto Developed rhenium and technetium complexes with capabilities of targeting the cell nucleus and binding to DNA for theranostic applications in cancer. Work involved organic synthesis, inorganic chemistry, radiochemistry, NMR spectroscopy, HPLC, column chromatography, cell culture, fluorescence microscopy.

Activities Young Professionals Council (SNMMI) (2015- present), Board Intern of the Center for Molecular Imaging Innovation and Translation (2012-2015), Graduate Student Council UBC Chemistry (2007- 2009). Reviewer for: Journal of the American Chemical Society, International Edition, Chemical Communications (RSC), Journal of Nuclear Medicine, Journal of , Chemistry A European Journal, Nanomedicine, Inorganic Chemistry, Journal of Inorganic Biochemistry, Nanoscale (RSC), Advanced Materials (), ACS Medicinal Chemistry Letters, Bioorganic & Medicinal Letters, Dalton Transactions, ChemMedChem, ChemPlusChem, PLOS ONE, Journal of Visualized Experiments (JoVE), Organometallics, Nuclear Medicine and Biology, Cancer Biotherapy and Radiopharmaceuticals (Editorial Board)

Teaching experience 2004-2006: General Chemistry Undergraduate Laboratory, University of Zurich. Supervised and instructed students in general chemistry techniques.

2007-2008: General Chemistry Undergraduate Laboratory, University of British Columbia. Supervised and instructed students in general chemistry techniques.

2008-2011: Inorganic Chemistry Undergraduate Laboratory, University of British Columbia. Supervised and instructed students in inorganic chemistry techniques.

2017 Fall: Organic Chemistry Laboratory Lecture (CHE 327)

2018 Spring - current: Inorganic Chemistry 1 (CHE 375), Stony Brook University. Development of course material, lecture, problem sets, examinations.

2019 Spring - current: Inorganic Chemistry 2 (CHE 376/514), Stony Brook University. Development of course material, lecture, problem sets, examinations.

Publications

1. Boros E, Hafeli UO, Patrick BO, Adam MJ, Orvig C. Design, Synthesis, and Imaging of Small Amphiphilic Rhenium and 99mTechnetium Tricarbonyl Complexes. Bioconjugate Chem. 2009, (20) 1002-1009. 2. Boros E, Ferreira CL, Cawthray JF, Price EW, Patrick BO, Wester DW, Adam MJ, Orvig C. Acyclic Chelate with Ideal Properties for 68Ga PET Imaging Agent Elaboration. J. Am. Chem. Soc. 2010, (132) 15726-1533.

3. Boros E, Ferreira CL, Patrick BO, Adam MJ, Orvig C. New Ga Derivatives of the H2dedpa Scaffold with Improved Clearance and Persistent Heart Uptake. Nucl. Med. Biol. 2011 (38), 1165-1174. 4. Boros E, Lin YHS, Ferreira, CL, Patrick BO, Hafeli UO, Adam MJ, Orvig C. One to chelate them all: investigation of a versatile, bifunctional chelator for 64Cu, 99mTc, Re and Co. Dalton Trans. 2011, (40), 6253-6259.

5. Boros E, Ferreira CL, Yapp DTT, Gill RK, Price EW, Adam MJ, Orvig C. Conjugates of the H2dedpa Scaffold: Synthesis, Labeling and Imaging with 68Ga. Nucl. Med. Biol. 2012, (39), 785-794.

6. Price EW, Cawthray JF, Bailey GA, Ferreira CL, Boros E, Adam MJ, Orvig C. H4octapa: An Acyclic Chelator for 111In Radiopharmaceuticals. J. Am. Chem. Soc. 2012, (134), 8670-8683.

7. Boros E, Cawthray JF, Ferreira CL, Adam MJ, Orvig C. Evaluation of the H2dedpa Scaffold and its cRGDyK Conjugates for Labeling with 64Cu. Inorg. Chem. 2012, (51), 6279-6284. 8. Ferreira CL, Yapp DTT, Mandel D, Gill RK, Boros E, Wong MQ, Jurek P, Kiefer GE. 68Ga Small Peptide Imaging: Comparison of NOTA and PCTA. Bioconjugate Chem. 2012, (23), 2239–2246. 9. Bayley GA, Price EW, Zeglis BM, Ferreira CL, Boros E, Lacasse MJ, Patrick, BO, Lewis, JS, Adam MJ, Orvig C. 67 64 111 177 H2azapa: a Versatile Acyclic Multifunctional Chelator for Ga, Cu, In, and Lu. Inorg. Chem. 2012 (51), 12575– 12589. 10. Boros E, Polasek M, Zhang Z, Caravan P. Gd(DOTAla) – A single amino acid Gd-complex as a modular tool for high relaxivity MR contrast agent development. J. Am. Chem. Soc. 201, (134), 19858–19868. 11. Boros E, Caravan P. Structure relaxivity relationships of serum albumin targeted MRI probes based on a single amino acid Gd complex. J. Med. Chem. 2013, (56), 1782–1786. 12. Yapp DTT, Ferreira CL, Gill RK, Boros E, Wong MQ, Mandel D, Jurek P, Kiefer GE. Imaging Tumor Vasculature Noninvasively with Positron Emission Tomography and RGD Peptides Labeled with -64 using the Bifunctonal Chelates DOTA, Oxo-DO3A and PCTA. Mol. Imaging. 2013, (12) 263-227. 13. Boros E,* Rybak-Akimova, E, Holland J, Rietz TA, Rotile NJ, Blasi F, Day H, Latifi R, Caravan P. Pycup – A bifunctional, cage-like ligand for 64Cu radiolabeling. Mol. Pharmaceutics. 2014, (11) 617–629. 14. Boros E, Karimi S, Kenton N, Helm L, Caravan P. Gd(DOTAlaP): Exploring the Boundaries of Fast Water Exchange in Gd-Based MRI Contrast Agents. Inorg. Chem. 2014(53) 6985-6994.

16. Ramogida CF, Cawthray JF, Boros E, Ferreira CL, Patrick BO, Adam MJ, Orvig C. H2CHXdedpa and H4CHXoctapa – Chiral Acyclic Chelating Ligands for 67/68Ga and 111In Radiopharmaceuticals. Inorg. Chem. 2015, (54), 2017–2031 17. Boros E, Caravan P. Probing the Structure-Relaxivity Relationship of Bishydrated Gd(DOTAla) Derivatives. Inorg. Chem. 2015, (54), 2403-2410. 18. Boros E, Bowen AM, Josephson L, Vasdev N, Holland JP. Chelate-free metal ion binding and heat-induced radiolabeling of oxide nanoparticles. Chem. Sci. 2015, (1), 225-236. 19. Boros E, Gale EM, Caravan P. MR Imaging Probes: Design and Applications. Dalton Trans. 2015, (44), 4804-4818. 20. Meimetis LG, Boros E,* Carlson JC, Ran C, Caravan P, Weissleder R. Bioorthogonal Fluorophore Linked DFO- Technology Enabling Facile Chelator Quantification and Multimodal Imaging of Antibodies. Bioconjugate Chem. 2016, (27), 257-263. 21. Boros E,* Holland JP, Kenton N, Rotile N, Caravan P. Macrocycle-Based Hydroxamate Ligands for Complexation and Immunoconjugation of 89Zirconium for Positron Emission Tomography (PET) Imaging. ChemPlusChem 2016, (81), 274-281. 3+ 22. Iki N, Boros E, Nakamura M, Baba R, Caravan P. Gd3TCAS2: An Aquated Gd -Thiacalix[4]arene Sandwich Cluster with Extremely Slow Ligand Substitution Kinetics. Inorg. Chem. 2016, 55, 4000-4005. 23. Ramogida, CF, Boros E, Patrick BO, Zeisler SK, Kumlin J, Adam, MJ, Schaffer P, Orvig, C. 2016. Evaluation of 64 H2CHXdedpa, H2dedpa-and H2CHXdedpa-N,N′-propyl-2-NI ligands for Cu(II) radiopharmaceuticals. Dalton Trans. 2016, (45), 13082-13090. 24. Boros E, Srinivas R, Kim H-K, Raitsimring A, Astashkin A, Poluektov O, Niklas J, Horning A, Tidor B, Caravan P. Intramolecular Hydrogen Bonding to Restrict Gd-Aqua Ligand Dynamics. Angew. Chem. Int. Ed. 2017, (20), 5603- 5606. 25. Adams CJ, Wilson JJ, Boros E.* Multifunctional desferrichrome analogues as versatile 89Zr(IV) chelators for immunoPET probe development. Mol. Pharmaceutics 2017, (14) 2831–2842 26. Knopf KM, Murphy BL, MacMillan SN, Baskin JM, Barr MP, Boros E, Wilson JJ. In Vitro Anticancer Activity and in Vivo Biodistribution of Rhenium(I) Tricarbonyl Aqua Complexes. J. Am. Chem. Soc. 2017, (139), 14302-14314. 27. Boros E,* Pinkhasov O, Caravan P. Metabolite profiling with HPLC-ICP-MS - a rapid and simple way to assess in vivo behavior of imaging probes. EJNMMI Radiopharm. Chem., 2018, (3), 2-6 28. Boros E,* Holland J. P.* Chemical aspects of metal ion in the synthesis and application of antibody- based radiotracers. J. Label. Compd. Radiopharm. 2018, (61), 652-671. 29. Ahn S.H., Boros E.* Nuclear and Optical Bimodal Imaging Probes Using Sequential Assembly: A Perspective. Cancer Biother Radiopharm. 2018, (8), 308-315. 30. Cosby A.G., Ahn S.H., Boros E.* Cherenkov Radiation Mediated In Situ Excitation of Discrete Luminescent Lanthanide Complexes. Angew. Chem. Int. Ed. 2018, 57, 15496-15499. 31. Boros E,* Packard A.B.* Radioactive transition metals for imaging and therapy. Chem Rev. 2019, (119), 870–901. 32. Ahn SH, Thach D, Vaughn B, Alford V, Preston A, Laughlin ST, Boros E.* Linear Desferrichrome-linked silicon- rhodamine antibody conjugate enables targeted multimodal imaging of HER2 in vitro and in vivo. Mol Pharmaceutics 2019, (16), 1412-1420 33. Konkankit CC, Vaughn B, McMillan SJ, Boros E., Wilson J.J. Combinatorial Synthesis to Identify a Potent, Necrosis-Inducing Rhenium Anticancer Agent. Inorg. Chem. 2019, (58), 3895-3909. 34. Cosby AG, Quevedo G, and Boros E.* A High-Throughput Method To Measure Relative Quantum Yield of Lanthanide Complexes for Bioimaging. Inorg. Chem. 2019; (58), 10611-10615 35. Racow EE, Kreinbihl J, Cosby AG, Yang Y, Pandey A, Boros E*, Johnson CJ*. General Approach to Direct Measurement of the Hydration State of Coordination Complexes in the Gas Phase: Variable Temperature Mass Spectrometry. J. Am. Chem. Soc. 2019, (141), 14650-14660. 36. Rodríguez-Rodríguez A, Shuvaev S, Rotile N, Jones CM, Probst CK, Dos Santos Ferreira D, Graham-O’Regan G, Boros E., Knipe RS, Griffith JW, Tager AM, Bogdanov A Jr, Caravan P. Peroxidase Sensitive Amplifiable Probe for Molecular Magnetic Resonance Imaging of Pulmonary Inflammation. ACS Sensors. 2019, (4), 2412-2419. 37. Pandey A, Savino C, Ahn SH, Yang Z, Van Lanen SG, Boros E.* Theranostic Gallium Siderophore Ciprofloxacin Conjugate with Broad Spectrum Antibiotic Potency. J. Med. Chem. 2019, (62), 9947-9960. 38. Vaughn BA, Ahn SH, Aluicio-Sarduy E, Devaraj J, Olson AP, Engle JW and Boros E.* Chelation with a Twist: A Bifunctional Chelator to Enable Room Temperature Radiolabeling and Targeted PET Imaging with Scandium-44. Chem. Sci. Chem. Sci. 2020, (11), 333 - 342 39. Aluicio-Sarduy E, Thiele NA, Martin KE, Vaughn BA, Devaraj J, Olson AP, Barnhart TA, Wilson JJ*, Boros E*, and Engle JW*. Establishing Radiolanthanum Chemistry for Targeted Nuclear Medicine Applications Chem. Eur. J. 2020, (26), 1238-1242

* = Denotes corresponding authorship.

Patent 1. Bifunctional Chelating Agents - PCT Patent Application WO2011100829. Filed as: EP3318555A1. Applications Co-inventor. The invention describes acyclic chelators for the fast and efficient radiolabeling with the radiometals 67/68Ga, 64Cu, 111In, and 177Lu.

2. Peptidic structures incorporating an amino acid metal complex and applications in magnetic resonance imaging - PCT Patent Application WO2014075079. Filed as US20150297761. Co-inventor. This application describes MRI contrast agents that have high relaxivity and high fields.

3. Triazamacrocycle-derived chelators for the coordination of imaging and therapy metal ions and methods of using same – Filed US application. Co-inventor. This application describes bifunctional chelators for rapid complexation of Cu and Sc isotopes.

Issued Patents 1. EP2536691B1: Bifunctional chelating agents (Issued by the European Patent Office) 2. JP5856982B2 Bifunctional chelating agents (Issued by Japan Patent Office) 3. US8772446 Bifunctional chelating agents (Issued in the US Patent Office)

Funding support (awarded)

a) Source of Support: Department of Defense Ovarian Cancer Research Program Pilot Award (Subcontract) Grant Number: W81XWH-17-1-0097 Title: Multimodal Theranostic Anticancer Complexes of Rhenium to Circumvent Resistance in Relapsed Ovarian Cancer Total Award Period Covered: 03/01/17 – 02/28/20 Total Amount (Direct): $23,838 (Subcontract – Wilson PI) Person Months Effort: 0.6 calendar months effort Goals of Project: This pilot award was funded to develop folate receptor-targeted rhenium anticancer agents for the treatment of ovarian cancer.

b) Source of Support: Industrial Research agreement with Sutro Biopharma Grant Number: n/A Title: Evaluation of site-specific 89Zr-anti-HER2 conjugates for PET imaging in nonclinical murine models Total Award Period Covered: 12/1/17 – 02/01/20 Total Amount (Direct): $8,410 Goals of Project: The purpose of this proof of concept study is the development of companion imaging tracers for site-specifically functionalized antibody drug conjugates and the assessment of their in vivo behavior in non-clinical murine models of disease (HER2+ ovarian cancer).

c) Source of Support: Long Island Bioscence Hub Grant Number: U01HL127522 - 18150031 Title: Radioactive Scandium Complexes to Image Prostate Cancer with Positron Emission Tomography Total Award Period Covered: 03/01/18 - 02/28/19 Total Amount (Direct): $49,999 Person Months Effort: 0 calendar month effort Goals of Project: Scandium radioisotopes provide opportunities for PET imaging and subsequent radiotherapy. However, the as the aqueous chemistry of Sc(III) is underexplored, effective chelation strategies are lacking. This REACH grant proposes to develop new chelation approaches to Sc(III) and apply them to image the prostate specific membrane antigen (PSMA) in a mouse xenograft model.

d) Source of Support: National Institute of Health Pathway to Independence Award K99/R00 (NHLBI) Grant Number: R00HL125728 Title: Development of Zr-89 based ImmunoPET agents for Idiopathic Pulmonary Fibrosis Total Award Period Covered: 02/01/18 - 01/31/21 Total Amount (Direct): $396,350 Person Months Effort: 2.4 calendar month effort Goals of Project: Idiopathic pulmonary fibrosis (IPF) is a progressively fibrotic, fatal lung disease with an average survival of only 2-3 years from the time of diagnosis. This proposal aims to develop a positron emission tomography imaging probe to noninvasively diagnose IPF, stage disease, monitor therapy response, to select patients that would benefit from new treatments for IPF currently in clinical trials.

e) Source of Support: Long Island Bioscence Hub Grant Number: U01HL127522 - 19150054 Title: Radioactive Scandium Complexes to Image and Treat Prostate Cancer Total Award Period Covered: 03/01/20 - 02/28/21 Total Amount (Direct): $100,000 Person Months Effort: 0 calendar month effort Goals of Project: This REACH grant utilizes previously developed chelation approaches to Sc(III) for the imaging and treatment of prostate cancer in preclinical models followed by preparation for clinical translation.

f) Source of Support: NSF CAREER Grant Number: CHE 1942434 Title: CAREER: Exploring Cherenkov Radiation for the In Situ Excitation of Discrete Luminescent Lanthanide Complexes Total Award Period Covered: 09/01/20 - 08/31/25 Total Amount (Direct): $405,000 Person Months Effort: 2.4 calendar month effort Goals of Project: This proposal aims to develop new discrete luminescent lanthanide complexes that can be efficiently excited with Cherenkov radiation emitted by radioactive isotopes utilized in nuclear medicine. This in situ excitation method paves the way for lanthanide-based optical imaging probes with enhanced depth penetration and improved biocompatibility.

Invited Lectures

12/2012 “Ga-68 PET Tracer Development: Coordination Chemistry to the Rescue” Nuclear Medicine and Molecular Imaging Seminar Series, MGH/HMS, Boston, MA, USA 08/2013 “Development of Metal-based PET and MR Imaging probes - Or two tales of how the ligand makes all the difference.” EPFL Lausanne, Switzerland. 08/2013 “Bimodal Imaging Probes: Design, Synthesis, and Applications” European Association of Nuclear Medicine (EANM) Annual Meeting, Lyon, France 11/2013 “Hot and Cold: Adventures in Coordination Chemistry for Molecular Imaging Agent Development”, JPNM seminar series, Harvard Medical School, Boston, USA 11/2013 “Adventures in Coordination Chemistry for Molecular Imaging Agent Development” Northeastern University, Chemistry Seminar Series, Boston, MA, USA 12/2013 “PET Imaging Agent Development with Radiometals” Annual WIN (Women in Nuclear) Meeting, Boston, MA, USA. 06/2014 “Hot and Cold: Adventures in Chelator Design for Molecular Imaging” 97th Canadian Chemistry Conference, Vancouver, BC, Canada 05/2015 “Optimizing Coordination Chemistry for Metal-based Imaging” Invited lecture, Universitatsklinikum Freiburg, Germany 03/2016 “Metal-based molecular imaging” Molecular Imaging Program Stanford (MIPS), Stanford, CA, USA 07/2017 “Molecular Imaging with Antibodies” Sutro Biopharma, South San Francisco, CA, USA 11/2017 “Multimodal ImmunoPET Probes”, City University of New York (CUNY) Radiometals symposium, New York, NY, USA 12/2017 “HPLC-ICP-MS: A powerful tool for metabolite profiling of metal-based tracers and therapeutics”, DKFZ Universitaetsklinikum Heidelberg, Germany 03/2018 “Zr-89 Based Multimodal Probes” ACS national spring meeting, New Orleans, USA. 04/2018 “Metal-Based Molecular Imaging” Boston Regional Inorganic Colloquium 46, Brown University, Providence, USA. 08/2018 “Cerenkov radiation mediated in situ excitation of lanthanide luminescence” European Biological Inorganic Chemistry Conference (EuroBIC), Birmingham University, Birmingham, UK. 09/2018 “From worker bee to queen bee: On the transition from postdoc to faculty” Educational program WMIC 2018, Seattle, USA . 10/2018 “In situ excitation of luminescent lanthanide complexes for biomedical imaging” Inorganic and Organometallic Topical Group of the NY ACS Local Section, Columbia University, New York City, USA 03/2019 Iona College, New Rochelle, USA, invited talk, “Tracing iron metabolism of bacteria to develop better diagnostics and therapeutics for infection: A medicinal inorganic chemistry challenge” 06/2019 ISMEC 2019, Debrecen, Hungary – Invited keynote address 06/2019 CSC 2019, Quebec City, Canada – Bioinorganic symposium, Invited talk, 06/2019 CSC 2019, Quebec City, Canada – Radiochemistry symposium, Invited talk 06/2019 NERM 2019, Saratoga Springs, USA – Radiochemistry symposium, Invited talk 10/2019 University of Kentucky School of Pharmacy – Departmental Seminar, Invited talk 12/2019 Hunter College, CUNY, Manhattan, NY – Departmental Seminar 02/2019 Brown University, Providence, RI – Departmental Seminar 03/2020 ACS national spring meeting, Radiotherapeutics symposium, Philadelphia, USA, Invited talk 03/2020 ACS national spring meeting, Award symposium for Katherine Franz, Philadelphia, USA, Invited talk 06/2020 29th Rare Earth Research Conference (RERC 29), Invited talk 06/2020 Metals in Medicine Gordon Conference, Andover, USA, Invited talk 08/2020 ACS national fall meeting, "Advances in Metallodrugs and Metallodiagnostics” symposium – declined 08/2020 EuroBIC 2020, Rejkjavik, Iceland – declined 10/2020 University of New Hampshire, Durham, NH – Departmental Seminar 12/2020 Pacifichem “Innovative Uses of Metals in Medicine Symposium”, Honolulu, USA, Invited talk 12/2020 Pacifichem “Metal anticancer agents with unconventional modes of action”, Honolulu, USA, Invited talk