Fatemeh Khodadustvaskasi

ESR18-  Molecular imaging of angiogenesis and therapeutic effects of anti-angiogenetic agents in rheumatoid arthritis

Studying radiology as my bachelor’s degree along with my master’s degree, radiopharmaceutical sciences, provide me with a comprehensive skills and broad view in wide variety of imaging modalities.

I have knowledge and experiences in radiopharmacy, radiolabeling, stability test, affinity assay,cell culture,biodistribution, human xenograft tumor mouse model, the preparation, quality control and supply of radiopharmaceuticals, biomolecules and labeled compounds, ability to work with analytical devices (TLC, HPLC) and also different imaging modalities, such as MRI, CT, X-ray tube, mammography, SPECT.

The title of my master’s thesis was “the influence of HYNIC chelator with Edda/Tricine as colignds on the specific uptake and the biodistribution of SSSLTVSPWYP peptide for imaging of ovarian cancer with overexpression of HER2”.

This developed peptide has been proven to exhibit high contrast tumor uptake both in biodistribution data and SPECT imaging which led to further examination by my knowledgeable research group to test it for clinical application. Simultaneously, I was involved in another project with the same peptide evaluating the influence of a co-ligand for improving the targeting and imaging of HER2 overexpression tumor. I have two publication related to my master thesis:

• “An improved 99mTc-HYNIC-(Ser)3-LTVSPWY peptide with EDDA/tricine as co-ligands for targeting and imaging of HER2 overexpression tumor. ” F. Khodadust, S. Ahmadpour, N. Aligholikhamseh, S.M. Abedi, S.J. Hosseinimehr, European Journal of Medicinal Chemistry, 2018. 144: p. 767-773.

DOI: https://doi.org/10.1016/j.ejmech.2017.12.037

Description: Overexpression of human epidermal receptor 2 (HER2) has given the opportunity for targeting delivery of anti-tumor drugs and radiotracers. The aim of this study was to evaluate the 99mTc-HYNIC-(EDDA/tricine)-(Ser3)-LTVSPWY peptide for tumor targeting and imaging of tumor with overexpression of HER2.

In our project, SSSLTVSPWY peptide was successfully labeled with 99mTc using HYNIC as chelator and EDDA/tricine co-ligands to overcome the problem of time-consuming double stage direct radiolabeling procedure, with an efficient output under the mild condition and improved in vitro and in vivo findings for tumor targeting compared to previously studied radiolabeled peptide (99mTc-Cys-Ser-Ser-Ser-LTVSPWY) by our research group. The proposed labeling method having advantages of a well-defined chemistry and the ability for post conjugation labeling in which the peptide is first conjugated with a BFCA and stored for later radiolabeling process. The result of my thesis turned out to be successful and became a subject for further experiment on clinical stage. For my project, radiolabeling, the in vitro stability, cellular affinity, animal biodistribution in

tumor bearing mice and imaging have been performed.

• ” 99mTc-HYNIC-(Ser)3-LTVPWY peptide bearing tricine as co-ligand for targeting and imaging of HER2 overexpression tumor.” N. Aligholikhamseh, S. Ahmadpour, F. Khodadust, S.M. Abedi, S.J Hosseinimehr, Radiochimica Acta, 2018. 106(7), 601-609.

DOI: https://doi.org/10.1515/ract-2017-2868

Description: In other project with the same peptide (99mTc-HYNIC-(tricine)-(Ser)3-LTVSPWY peptide) labeling procedure have been evaluated with different coligand (tricine). It was investigated for HER2 binding affinity, targeting and imaging of HER2+ ovarian cancer. This radiolabeled peptide exhibited in vitro affinity and in vivo tumor targeting. The HYNIC-(Ser)3-LTVSPWY peptide was successfully labeled with 99mTc using tricine as a co-ligand at room temperature in order to make the radiolabeling procedure easier without the need for heating. Using tricine as coligand and tri-serine as spacer give a hydrophilic nature to this radiolabeled peptide which lead to fast clearance from kidneys and blood leading to rapid washout from non-targeted tissues in xenografted nude mice.The tumor/muscle ratio of 99mTc-HYNIC-peptide was lower than cysteine based peptide and tumor uptake was visualized at 4 h after injection of 99mTc-HYNIC-tricine-(Ser)3 LTVSPWY in SPECT imaging. For labeling of this peptide with 99mTc , practicing other co-ligands and chelators to achieve better tumor targeting and imaging is recommended.

My academic background:

September2015- May 2018	Master’s Degree in Radiopharmaceutical Sciences Mazandaran University of Medical Sciences Sari, Mazandaran Province, Iran   Thesis title: The Influence of HYNIC Chelator with EDDA/Tricine as Colignds on the Specific Uptake and the Biodistribution of SSSLTVSPWYP Peptide for Imaging of Ovarian Cancer with Overexpression of HER2 Thesis Supervisor: Prof. Seyed Jalal Hosseinimehr
February 2013- February 2015	Bachelor’s Degree in Radiology Mazandaran University of Medical Sciences Sari, Mazandaran Province, Iran
September2007-July 2009	Associate’s Degree in Radiology Mazandaran University of Medical Sciences Sari, Mazandaran Province, Iran