OMB No. 0925-0001 and 0925-0002 (Rev. 10/2021 Approved Through 01/31/2026)

NAME: Hanieh Karimi

eRA COMMONS USER NAME (credential, e.g., agency login): hk0050

POSITION TITLE: Postdoctoral fellow

EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable. Add/delete rows as necessary.)

1. Personal Statement

 I am a Postdoctoral Fellow at the department of Radiology, Nemours Children’s Health, Wilmington, Delaware. My research is mainly in the field of cancer studies, tumor targeting, drug delivery, radiopharmaceutical biodistribution, quality control of drugs and radiolabeled compounds, SPECT/PET/MRI imaging, animal model, and data analysis. I have earned a Ph.D. in Biophysics with a focus on tissue engineering, bioluminescence techniques, micro-CT imaging, o-Ps (new biomarker) to differentiate between malignant and non-malignant tumors, glucose distribution in tumor cells and hypoxia. My research journey has been driven by a passion for advancing cancer diagnosis and treatment through innovative approaches, from developing novel radiolabeled peptides for glioma detection to exploring the properties of 3D melanoma cell cultures and delving into Immunotherapy and Immuno-PET imaging.

 My foundational education equipped me with the skills to use medical imaging tools for cancer detection. I gained expertise in preparing radiopharmaceuticals for various diseases, including cancer and image analysis.

 I pursued an advanced degree to expand my expertise in tumor targeting, drug delivery, radiopharmaceutical biodistribution, quality control of drugs and radiolabeled compounds, and data analysis. My research was centered on the development of a novel radiolabeled peptide (RGD) designed to specifically target glioma cancer cells using Tc-99m for precise detection. During this phase, my objective was to enhance the specific targeting of glioma cancer cells, particularly in malignant brain tumors, through the utilization of a newly developed radiolabeled peptide. This effort aimed to reduce the background-to-tumor ratio, a crucial factor in cancer cell recognition. The improved specificity not only facilitates the surgeon in accurately determining the tumor's location, size, and shape before removal but also assists radio pharmacists and doctors in making informed decisions about the subsequent steps of treatment.

My doctoral research involved the use of 3D cell cultures (spheroids) to bridge the gap between in vitro and in vivo conditions. I explored the physiological and morphological characteristics of metastatic and non-metastatic melanoma cells, utilizing bioluminescence techniques and micro-CT imaging. 3D spheroids, with their multi-layer structures, mimic the physiological and anatomical properties of real tumors. Comparing 3D cell cultures to monolayers revealed specific physiological and morphological characteristics, including cell-to-cell and cell-matrix interactions, cell signaling, proliferation, necrosis, and metastasis. Subsequently, I studied the lifetime of o-Ps (a new biomarker) in two melanoma spheroids with different malignancy rates—WM266-4 as a malignant melanoma cell line and WM115 as a primary melanoma cell line. These studies aimed to determine if cancer cells at different stages exhibit distinct molecular properties, as indicated by the o-Ps lifetime measurement. Exploring the uptake rate of essential nutrients such as glucose and oxygen in cancer cells, I investigated the dependency of o-Ps lifetime on milieu characteristics using 3D spheroids.

One of my significant accomplishments is successful immunotherapy and anticipation of immunotherapy responses using Anti-CD69 diabody to target T-cells in glioblastoma mice model, where I worked on Immunotherapy and Immuno-PET imaging utilizing CD69 diabody which is the early activator on T-cells in GBM microenvironment. In this project, I conjugated purified Diabody with an appropriate chelator, NOTA, then radiolabeled with radiotracer Cu-64. Different In vitro studies such as BCA assay, SDS-PAGE, ELISA, Immunoreactivity, Cell based assay and stability tests were performed to evaluate the different properties of conjugated and radiolabeled CD69-Db. I also cultured GL261 cells for mice brain inoculation. In this project, I have done brain surgery on mice to inoculate GL261 cells on mouse brain. PET-CT and MRI imaging was done to evaluate the tumor properties and radiotracer uptake in mice brains. I conducted immunotherapy (ICI therapy) after tumor inoculation to determine the T-cell activation in the GBM microenvironment. During my scientific journey, my works have been published in reputable journals such as nature communication, Science advances, Scientific reports and cancer research communication. I have also presented at major conferences, earning recognition for the best abstracts and talks.

2. Positions, Scientific Appointments and Honors

Positions, Scientific Appointments

2022-2024        Postdoctoral Fellow, University of Missouri, Columbia, MO

2024-Present    Postdoctoral Fellow, Nemours Children’s Health, Wilmington, DE

      Honors

• Invited speaker for the best abstract in Ellis Fishel Cancer Research, Columbia, Mo, 2024
• Selected as one of the best abstracts in SNMMI conference and invited speaker, Chicago, 2023
• Gain 1st place in PhD of Biophysics in Jagiellonian university. 2020
• Gain ranking 1 student scholarship from Jagiellonian university. 2020  
• Selected as the best speaker in the Nano Tech Poland 2021 Conference.                                                 
• Gain IUBMB Special Meeting Fellowship. 2020
• Gain scholarship from Faculty of Physics, Astronomy, and applied computer sciences for new research proposal in second year of Ph.D. 2020
• Gain scholarship from Faculty of Physics, Astronomy and applied computer sciences for new research proposal in first year of Ph.D. 2019
• Gain scholarship from The Foundation for Polish Science and join to J-PET team project. 2018
• Gain 3rd place in university entrance exam, master’s degree.2014
• Achieved 2nd place in university entrance exam, BSc. Degree.2012    

3. Contributions to Science

1. Development of the ¹⁸F labeled vorasideni

Vorasidenib is a recently FDA-approved small molecule that targets mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2), which are implicated in various gliomas, including glioblastoma, the most aggressive form of brain cancer. While vorasidenib shows promise in treating IDH-mutant gliomas, glioblastoma remains challenging to diagnose and monitor due to its heterogeneity and infiltrative nature. Fluorine-18 PET imaging offers a noninvasive and highly sensitive method to visualize metabolic and molecular processes in real time. By radiolabeling vorasidenib with F-18, researchers aim to develop a novel imaging tool for assessing IDH activity, enabling more accurate diagnosis, treatment planning, and monitoring of glioblastoma, ultimately improving patient outcomes.

2. Preclinical evaluation of the ¹⁸F-vorasideni in glioma animal model using PET imaging

During my postdoctoral fellowship, I played a pivotal role in advancing PET radiotracers designed to target specific receptors within the tumor microenvironment, with the goal of monitoring immune responses to cancer therapies. A successful biomarker requires high binding affinity, stability in vivo, and specificity to effectively target receptors for both diagnostic and therapeutic applications. My work integrated diverse disciplines, including conjugation chemistry, radiochemistry, biology, drug delivery, antibody and peptide purification, biochemical assays, and immuno-oncology. I also gained substantial hands-on experience with animal models, particularly in tumor cell inoculation and brain surgeries in mice, enabling me to explore immunotherapeutic interventions in depth. This work, published in Cancer Research Communications (2023, H. Karimi et al.), highlighted my contributions to cancer immunotherapy research. Currently, we aim to develop a glioma xenograft model with high IDH expression and evaluate tumor progression through immunohistochemistry (IHC), in vitro studies, and PET imaging. Our goal is to establish correlations between PET imaging results and tumor stage, leveraging [18F]vorasidenib as a potential tool for assessing tumor malignancy, improving diagnostic accuracy, and monitoring therapeutic outcomes.

       D. Scholastic Performance

1. 3D melanoma spheroid model for the development of positronium biomarkers. H. Karimi, P. Moskal, A. Żak & E. Stępień. Scientific Reports, 2023. PMCID: PMC10175546, DOI: 10.1038/s41598-023-34571-4

2. Testing CPT symmetry in ortho-positronium decays with positronium annihilation tomography. P. Moskal , A. Gajos , M. Mohammed, J. Chhokar, N. Chug, C. Curceanu , E. Czerwiński ,M. Dadgar, K. Dulski , M. Gorgol , J. Goworek , B. C. Hiesmayr , B. Jasińska, K. Kacprzak, Ł. Kapłon, H. Karimi, D. Kisielewska, K. Klimaszewski, G. Korcyl, P. Kowalski, N. Krawczyk, W. Krzemień, T. Kozik, E. Kubicz, S. Niedźwiecki, S. Parzych, M. Pawlik-Niedźwiecka, L. Raczyński, J. Raj, S. Sharma , S. Choudhary, R. Y. Shopa, A. Sienkiewicz , M. Silarski, M. Skurzok, E. Ł. Stępień, F. Tayefi & W. Wiślicki. Nature communications, 2021. PMCID: PMC8476595, DOI: 10.1038/s41467-021-25905-9

3. Positronium imaging with the novel multiphoton PET scanner. P. Moskal, K. Dulski, N. Chug, C. Curceanu, E. Czerwiński, M. Dadgar, J. Gajewski, A. Gajos, G. Grudzień, B. Hiesmayr,

K. Kacprzak, Ł. Kapłon, H. Karimi, K. Klimaszewski, G. Korcyl, P. Kowalski, T. Kozik, N. Krawczyk, W. Krzemień, E. Kubicz, P. Małczak, S. Niedźwiecki, M. Pawlik-Niedźwiecka, M. Pędziwiatr, L. Raczyński, J. Raj, A. Ruciński, S. Sharma, Shivani, R. Shopa, M. Silarski, M. Skurzok, E. Stępień, M. Szczepanek, F. Tayefi, W. Wiślicki. Science advances. 2021.DOI: 10.1126/sciadv.abh4394 PMCID: PMC11559468, DOI: 10.1126/sciadv.abh4394

4. Immuno-PET Imaging of CD69 Visualizes T-Cell Activation and Predicts Survival Following Immunotherapy in Murine Glioblastoma. M. Nisnboym, S. Vincze, Z. Xiong, C. Sneiderman, R. Raphael, B. Li, A. Jaswal, R. Sever, K. Day, J. LaToche, L. Foley, H. Karimi, T.K Hitchens, S. Agnihotri, B. Hu, D. Rajasundaram, C. Anderson, D. Blumenthal, T. Pearce, S. Uttam, J. Nedrow, A. Panigrahy, I. Pollack, F. Lieberman, J. Drappatz, I. Raphael, W. Edwards, and G. Kohanbash. Cancer Research Communications. 2023. PMCID: PMC10324623, DOI: 10.1158/2767-9764.CRC-22-0434

5. Estimating the relationship between the Time Over Threshold and energy loss by photons in plastic scintillators used in the J-PET scanner. S. Sharma , J. Chhokar , C. Curceanu , E. Czerwiński , M. Dadgar , K. Dulski , J. Gajewski , A. Gajos , M. Gorgol , N. Gupta-Sharma , R. Del Grande , B. C. Hiesmayr , B. Jasińska , K. Kacprzak , Ł. Kapłon , H. Karimi , D. Kisielewska , K. Klimaszewski , G. Korcyl , P. Kowalski , T. Kozik , N. Krawczyk , W. Krzemień , E. Kubicz , M. Mohammed , Sz. Niedzwiecki , M. Pałka , M. Pawlik-Niedźwiecka , L. Raczyński , J. Raj , A. Ruciński , S. Shivani , R. Y. Shopa , M. Silarski , M. Skurzok , E. Ł. Stępień , W. Wiślicki , B. Zgardzińska , P. Moskal. EJNMMI Phys. 2020. PMCID: PMC7275104, DOI:10.1186/s40658-020-00306-x

6. Performance assessment of the 2gamma positronium imaging with the total-body PET scanners. P. Moskal , D. Kisielewska , R. Y. Shopa , Z. Bura , J. Chhokar , C. Curceanu , E. Czerwiński , M. Dadgar , K. Dulski , J. Gajewski , A. Gajos , M. Gorgol , R. Del Grande , B. C. Hiesmayr , B. Jasińska , K. Kacprzak , A. Kamińska , Ł. Kapłon , H. Karimi , G. Korcyl , P. Kowalski , N. Krawczyk , W. Krzemień , T. Kozik , E. Kubicz , P. Małczak , M. Mohammed , Sz. Niedźwiecki , M. Pałka , M. Pawlik-Niedźwiecka , M. Pędziwiatr , L. Raczyński , J. Raj , A. Ruciński , S. Sharma , S. Shivani , M. Silarski , M. Skurzok , E. Ł. Stępień , S. Vandenberghe , W. Wiślicki , B. Zgardzińska  EJNMMI Phys. 2020.  PMCID: PMC7326848, DOI:10.1186/s40658-020-00307-  w

7. Synchronisation and calibration of the 24-modules J-PET prototype with a 300 mm axial field of view. P. Moskal, T. Bednarski , Sz. Nied´zwiecki , M. Silarski , E. Czerwi´nski , T. Kozik , J. Chhokar , M. Bała , C. Curceanu , R. Del Grande , M. Dadgar , K. Dulski , A. Gajos , M. Gorgol , N. Gupta-Sharma , B. C. Hiesmayr , B. Jasi´nska , K. Kacprzak , Ł. Kapłon , H. Karimi , D. Kisielewska , K. Klimaszewski , G. Korcyl , P. Kowalski , N. Krawczyk , W. Krzemie´n , E. Kubicz , M. Mohammed , M. Pałka , M. Pawlik-Nied´zwiecka , L. Raczy´nski , J. Raj , S. Sharma , Shivani , R. Y. Shopa , M. Skurzok , E. St¸epie´n , W. Wi´slicki , and B. Zgardzi´nska. IEEE Transactions on Instrumentation and Measurement. DOI: 10.1109/TIM.2020.3018515

8. From tests of discrete symmetries to medical imaging with J-PET detector. P. Moskal, J. Baran, N. Chug, C. Curceanu, E. Czerwiński, M. Dadgar, K. Dulski, J. Gajewski, A. Gajos, M. Gorgol, B.C. Hiesmayr, B. Jasinska, K. Kacprzak, Ł. Kapłon, H. Karimi, K. Klimaszewski, P. Konieczka, G. Korcyl, T. Kozik, N. Krawczyk, W. Krzemień, E. Kubicz, D. Kumar, S. Niedźwiecki, D. Panek, S. Parzych, E. Perez, L. Raczyński, J. Raj, A. Ruciński, S. Sharma, S. Shivani, R.Y. Shopa, M. Silarski, M. Skurzok, E.Ł. Stępień, M. Szczepanek, F. Tayefi and W. Wiślicki. 2022. POS Proceedings of Science. DOI:10.22323/1.380.0033

9. The J-PET detector-a tool for precision studies of ortho-positronium decays. K. Dulski, S.D. Bass, J. Chhokar, N. Chug, C. Curceanu, E. Czerwiński, M. Dagdar, J. Gajewski , A. Gajos, M. Gorgol, R. DelGrande, B.C. Hiesmayr, B. Jasińska, K. Kacprzak, Ł. Kapłon, H. Karimi, D. Kisielewska, K. Klimaszewski, P. Kopka, G. Korcyl, P. Kowalski, T. Kozik, N. Krawczyk, W. Krzemień, E. Kubicz, P. Małczak, M. Mohammed, Sz. Niedźwiecki, M. Pałka , M. Pawlik-Niedźwiecka, M. Pędziwiatr, L. Raczyński, J. Raj, A. Ruciński, S. Sharma, Shivani, R.Y. Shopa, M. Silarski, M. Skurzok, E.Ł. Stępień, F. Tayefi, W. Wiślicki, B. Zgardzińska, P. Moskal.   Nuclear Inst. and Methods in Physics Research, A. 2021. DOI:10.1016/j.nima.2021.165452

10. X-ray microtomography as a new approach for imaging analysis tumor spheroids. H. Karimi , B. Leszczyński , T. Kołodziej, E. Kubicz , M. Przybyło, E. Stępień. Micron, 2020.  PMID: 32693343   DOI: 10.1016/j.micron.2020.102917

11. Radiochemical Evaluation and In Vitro Assessment of the Targeting Ability of a Novel 99mTc-HYNIC-RGD for U87MG Human Brain Cancer Cells. H. Karimi , N. Sadeghzadeh, S. Abediankenari , F. Rezazadeh, F. Hallajian. Current Radiopharmaceuticals, 2017. PMID: 28681701, DOI:10.2174/1874471010666170706164016

12. Melanoma Spheroids as a Model for Cancer Imaging Study. E. ł. Stępień, H. Karimi, B. Leszczyński, M. Szczepanek. Acta Phys. Pol. B. 2020. DOI: 10.5506/aphyspolb.51.159

13. Evaluation of toxicity and anti-tumor the effects of resverator and doxorubicin in MCF-7 tumor-bearing mice. F. Hallajian, M. Ghasmi , S. M. Abedi, R. Behzadi, E. Hayati , N. Sadeghzadeh, F. Rezazadeh, H. Karimi .  Cancer Biotherapy & Radiopharmaceuticals , 2018.  PMID: 30040447, DOI:10.1089/cbr.2018.2523

14. First observation of ortho-positronium with the J-PET tomograph. K. Dulski, S.D. Bass, J. Chhokar, N. Chug, C. Curceanu, E. Czerwiński, M. Dadgar, J. Gajewski, A. Gajos, M. Gorgol, R. Del Grande, B.C. Hiesmayr, B. Jasińska, K. Kacprzak, Ł. Kapłon, H. Karimi, D. Kisielewska, K. Klimaszewski, P. Kopka, G. Korcyl, P. Kowalski, T. Kozik, N. Krawczyk, W. Krzemień, E. Kubicz, P. Małczak, M. Mohammed, S.z. Niedźwiecki, M. Pałka, M. Pawlik-Niedźwiecka, M. Pędziwiatr, L. Raczyński, J. Raj, A. Ruciński, S. Sharma, R.Y. Shopa, M. Silarski, M. Skurzok, E.Ł. Stępień, F. Tayefi, W. Wiślicki, B. Zgardzińska, P. Moskal. HEP: arXiv:2006.07467

• Complete List of Published Work in Google Scholar:

             https://scholar.google.com/citations?user=aI5KeCQAAAAJ&hl=en