Chacko, Ann-Marie

PhD

Assistant Professor

Cancer & Stem Cell Biology Programme

+65 6601 1671

Email 1:

ann-marie.chacko@duke-nus.edu.sg

https://www.duke-nus.edu.sg/vivo-molecular-imaging-facility

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Research

Research Interest:

Translational Image-Guided Drug Delivery with Radiopharmaceuticals

Molecularly targeted agents have tremendous potential as specific drug-delivery vehicles, for a variety of relevant diseases, such as adult and pediatric cancer, inflammation, and infectious disease. In addition, they can be used as specific and/or sensitive diagnostics agents to detect the presence of cancer cells, and other pathologic tissues. The Chacko Laboratory combines unique expertise in radiopharmaceutical chemistry, biochemistry, pharmacology, and in vivo nuclear/fluorescent imaging and therapy. The goal is to develop and fully characterize ligands and drug delivery systems directed to different molecular targets, be they stand-alone diagnostics and therapeutics, or combined “theranostics”.

The laboratory has several active areas of research, including those listed below, which strongly complement the translational, and clinical research programmes of our collaborators at Duke-NUS, SGH, NTU, and internationally:

1. Platform technologies for imaging cancer immunotherapy;

2. Image-guided delivery approaches for overcoming the systemic blood-brain barrier;

3. Optimization and translation of small molecule radiotherapeutic ¹³¹I-MIBG for neuroendocrine cancers; and

4. Development of imaging biomarkers in infectious disease as surrogate clinical endpoints in disease management.

Selected Publications:

Cancer Imaging

• Chacko AM, Li C, Nayak M, Mikitsh JL, Hu J, Hou C, Grasso L, Nicolaides NC, Muzykantov VR, Divgi CR, Coukos G. Development of 124I-Immuno-PET Targeting Tumor Vascular TEM1/Endosialin. J Nucl Med. 55(3): 500-7. (2014) (Highlighted as Top Story: SNMMI SmartBrief Feb 2014 Molecular Imaging News)

• Chacko AM, Blankemeyer E, Lieberman BP, Qu W, Kung HF. 5-[18F]Fluoroalkyl pyrimidine nucleosides: probes for positron emission tomography imaging of herpes simplex virus type 1 thymidine kinase gene expression. Nucl Med Biol. 36(1):29-38. (2009) (Highlighted in: SNM PET Center of Excellence Newsletter 2009)

Infectious Disease Imaging

• Victorio CBL, Tham JY, Watanabe S, Sekula A, Ong J, Reolo MJ, Low J, Vasudevan SR, Chacko AM. FDG-PET/CT imaging of Zika virus infection in a murine model. J Nucl Med. 59(1):448. (2018)

• Chacko AM, Watanabe S, Herr KJ, Kalimuddin S, Serrano RMF, Ong J, Tham JY, Reolo M, Cheung YB, Low JGH, Vasudevan SG. 18F-FDG as an Inflammation Biomarker for Imaging Dengue Virus Infection and Treatment Response. JCI Insight. 2(9):e93474. (2017) (Media Highlights: EurekaAlert, ScienceDaily, Infectious Disease Hub, BioSpectrumAsia)

Brain Drug Delivery

• Mikitsh JM, Chacko AM. Pathways for small molecule delivery to the central nervous system across the blood brain barrier. Perspect Medicin Chem. 6:12-44. (2014)

• Chacko AM, Li C, Pryma DA, Brem S, Coukos G, Muzykantov VR. Delivery of antibody-targeted therapeutic and imaging agents to CNS tumors: crossing the blood-brain barrier divide. Expert Opin Drug Delivery. 10(7): 907-26. (2013) (Editorial pick July 2013)

Pulmonary Drug Delivery And Imaging

• Kiseleva R, Greineder CF, Villa CH, Hood ED, Albelda SM, Chacko AM, Abraham V, DeLisser HM, and Muzykantov VR. Mechanism of collaborative enhancement of binding of paired antibodies to distinct epitopes of PECAM-1. PLoS One. 12(1): e0169537. (2017)

• Chacko AM, Han JY, Greineder CF, Zern BJ, Mikitsh JL, Nayak M, Menon D, Johnston IH, Poncz M, Eckmann DM, Davies PF and Muzykantov VR. Enhancement of nanocarrier targeting to vascular endothelium via collaborative epitope engagement. ACS Nano. 9(7):6785-93. (2015)

Nanomaterial Contrast Agents

• Tang C, York AW, Mikitsh JL, Wright AC, Chacko AM,Elias DR. Xu Y, Lim HK, Prud’homme RK. Preparation of PEGylated Iodine‐Loaded Nanoparticles via Polymer‐Directed Self‐Assembly. Macromol. Chem. Phys. 219 (11):1700592. (2018)

• Choi H, Liu T, Qiao H, Chacko AM, Hu SH, Chen SY, Zhou R, Chen IW. Biomimetic nano-surfactant stabilizes sub-50 nanometer phospholipid particles enabling high paclitaxel payload and deep tumor penetration. Biomaterials. 181:240-251. (2018)

• Tang C, Edelstein J, Mikitsh JL, Xiao E, Hemphill III AH, Pagels R, Chacko AM, and Prud’homme RK. Biodistribution and pharmacokinetics of core-labeled 125I polymeric nanoparticle prepared by Flash NanoPrecipitation (FNP). J Material Chem B Mater Biol Med. 4(14):2428-2434. (2016)

• Paik TJ, Chacko AM, Mikitsh JL, Pryma DA, Friedberg J and Murray CB. Synthesis of yttrium-90 doped rare earth metal nanocrystals for multimodality imaging. ACS Nano. 9(9):8718-8728. (2015)

Radiochemistry

• Janabi M, Pollack C, Chacko AM, Hunter DH. Resin-Supported Arylstannanes as Precursors for Radiolabeling with Iodine: Benzaldehydes, Benzoic acids, Benzamides and NHS ester. Can J Chem. 93(2): 207-217. (2015)

• Chacko AM, Divgi CR. Radiopharmaceutical chemistry with iodine-124: A non-standard radiohalogen for Positron Emission Tomography. Med Chem. 7(5): 388-405. (2011)

Other Contrast Agents

• Cook S, Ng B, Dong J, Viswanathan S, Dagostino G, Widjaja A, Lim WW, Ko N, Tan J, Chothani S, Huang B, Xie C, Chacko AM, Guimaraes-Camboa N, Evans S, Byrne A, Maher T, Liang J, Noble P, Schafer S. IL-11 is a therapeutic target in idiopathic pulmonary fibrosis. bioRxiv. 336537. (2018) doi: https://doi.org/10.1101/336537

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