Bio

Honors & Awards


  • Student travel Award, World Molecular Imaging Congress (2018)
  • Vevo Travel Award, Molecular Imaging Track, Fujifilm/VisualSonics (2018)
  • Faculty of Health Sciences Graduate Programs Outstanding Thesis Award, McMaster University (2017)
  • Faculty of Health Sciences Graduate Programs Excellence Award, McMaster University (2016)
  • McMaster Graduate Studies International Excellence Award, McMaster University (2014-2015)
  • Outstanding Oral Presentation Award, Faculty of Health Sciences, McMaster University (2014)
  • Chemical Biology Travel Award, McMaster University (2012-2013)
  • McMaster Graduate Studies International Excellence Award, McMaster University (2012-2013)

Professional Education


  • Doctor of Philosophy, McMaster University (2016)
  • Bachelor of Science, King Saud University (2009)

Stanford Advisors


Patents


  • Aimen Zlitni, John F. Valliant. "CanadaTargeted Molecular Imaging Contrast Agents.", Aug 1, 2015

Research & Scholarship

Projects


  • The development and evaluation of probes for multimodal molecular imaging of bacterial infections, Stanford University (12/2016 - Present)

    Imaging modalities include Photo-acoustic, fluorescence and PET imaging

    Location

    California

  • The preparation and evaluation of nanobubbles for photo-acoustic and Ultrasound molecular imaging of cancer, Stanford University (9/1/2016 - Present)

    Location

    California

Publications

All Publications


  • Molecular imaging agents for ultrasound. Current opinion in chemical biology Zlitni, A., Gambhir, S. S. 2018; 45: 113–20

    Abstract

    Ultrasound (US) imaging is a safe, sensitive and affordable imaging modality with a wide usage in the clinic. US signal can be further enhanced by using echogenic contrast agents (UCAs) which amplify the US signal. Developments in UCAs which are targeted to sites of disease allow the use of US imaging to provide molecular information. Unfortunately, traditional UCAs are too large to leave the vascular space limiting the application of molecular US to intravascular markers. In this mini review, we highlight the most recent reports on the application of molecular US imaging in the clinic and summarize the latest nanoparticle platforms used to develop nUCAs. We believe that the highlighted technologies will have a great impact on the evolution of the US imaging field.

    View details for PubMedID 29631121

  • Molecular imaging agents for ultrasound Current Opinion in Chemical Biology Zlitni, A., Gambhir, S. S. 2018; 45: 113-120
  • Development of prostate specific membrane antigen targeted ultrasound microbubbles using bioorthogonal chemistry. PloS one Zlitni, A., Yin, M., Janzen, N., Chatterjee, S., Lisok, A., Gabrielson, K. L., Nimmagadda, S., Pomper, M. G., Foster, F. S., Valliant, J. F. 2017; 12 (5): e0176958

    Abstract

    Prostate specific membrane antigen (PSMA) targeted microbubbles (MBs) were developed using bioorthogonal chemistry. Streptavidin-labeled MBs were treated with a biotinylated tetrazine (MBTz) and targeted to PSMA expressing cells using trans-cyclooctene (TCO)-functionalized anti-PSMA antibodies (TCO-anti-PSMA). The extent of MB binding to PSMA positive cells for two different targeting strategies was determined using an in vitro flow chamber. The initial approach involved pretargeting, where TCO-anti-PSMA was first incubated with PSMA expressing cells and followed by MBTz, which subsequently showed a 2.8 fold increase in the number of bound MBs compared to experiments performed in the absence of TCO-anti-PSMA. Using direct targeting, where TCO-anti-PSMA was linked to MBTz prior to initiation of the assay, a 5-fold increase in binding compared to controls was observed. The direct targeting approach was subsequently evaluated in vivo using a human xenograft tumor model and two different PSMA-targeting antibodies. The US signal enhancements observed were 1.6- and 5.9-fold greater than that for non-targeted MBs. The lead construct was also evaluated in a head-to-head study using mice bearing both PSMA positive or negative tumors in separate limbs. The human PSMA expressing tumors exhibited a 2-fold higher US signal compared to those tumors deficient in human PSMA. The results demonstrate both the feasibility of preparing PSMA-targeted MBs and the benefits of using bioorthogonal chemistry to create targeted US probes.

    View details for DOI 10.1371/journal.pone.0176958

    View details for PubMedID 28472168

  • In vivo Biodistribution of Radiolabeled Acoustic Protein Nanostructures. Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging Le Floc'h, J., Zlitni, A., Bilton, H. A., Yin, M., Farhadi, A., Janzen, N. R., Shapiro, M. G., Valliant, J. F., Foster, F. S. 2017

    Abstract

    Contrast-enhanced ultrasound plays an expanding role in oncology, but its applicability to molecular imaging is hindered by a lack of nanoscale contrast agents that can reach targets outside the vasculature. Gas vesicles (GVs)-a unique class of gas-filled protein nanostructures-have recently been introduced as a promising new class of ultrasound contrast agents that can potentially access the extravascular space and be modified for molecular targeting. The purpose of the present study is to determine the quantitative biodistribution of GVs, which is critical for their development as imaging agents.We use a novel bioorthogonal radiolabeling strategy to prepare technetium-99m-radiolabeled ([(99m)Tc])GVs in high radiochemical purity. We use single photon emission computed tomography (SPECT) and tissue counting to quantitatively assess GV biodistribution in mice.Twenty minutes following administration to mice, the SPECT biodistribution shows that 84 % of [(99m)Tc]GVs are taken up by the reticuloendothelial system (RES) and 13 % are found in the gall bladder and duodenum. Quantitative tissue counting shows that the uptake (mean ± SEM % of injected dose/organ) is 0.6 ± 0.2 for the gall bladder, 46.2 ± 3.1 for the liver, 1.91 ± 0.16 for the lungs, and 1.3 ± 0.3 for the spleen. Fluorescence imaging confirmed the presence of GVs in RES.These results provide essential information for the development of GVs as targeted nanoscale imaging agents for ultrasound.

    View details for DOI 10.1007/s11307-017-1122-6

    View details for PubMedID 28956265

  • Catching Bubbles: Targeting Ultrasound Microbubbles Using Bioorthogonal Inverse-Electron-Demand Diels-Alder Reactions ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Zlitni, A., Janzen, N., Foster, F. S., Valliant, J. F. 2014; 53 (25): 6459-6463

    View details for DOI 10.1002/anie.201402473

    View details for Web of Science ID 000337095900025

    View details for PubMedID 24829138

  • Trop2 is a driver of metastatic prostate cancer with neuroendocrine phenotype via PARP1. Proceedings of the National Academy of Sciences of the United States of America Hsu, E. C., Rice, M. A., Bermudez, A., Marques, F. J., Aslan, M., Liu, S., Ghoochani, A., Zhang, C. A., Chen, Y. S., Zlitni, A., Kumar, S., Nolley, R., Habte, F., Shen, M., Koul, K., Peehl, D. M., Zoubeidi, A., Gambhir, S. S., Kunder, C. A., Pitteri, S. J., Brooks, J. D., Stoyanova, T. 2020

    Abstract

    Resistance to androgen deprivation therapy, or castration-resistant prostate cancer (CRPC), is often accompanied by metastasis and is currently the ultimate cause of prostate cancer-associated deaths in men. Recently, secondary hormonal therapies have led to an increase of neuroendocrine prostate cancer (NEPC), a highly aggressive variant of CRPC. Here, we identify that high levels of cell surface receptor Trop2 are predictive of recurrence of localized prostate cancer. Moreover, Trop2 is significantly elevated in CRPC and NEPC, drives prostate cancer growth, and induces neuroendocrine phenotype. Overexpression of Trop2 induces tumor growth and metastasis while loss of Trop2 suppresses these abilities in vivo. Trop2-driven NEPC displays a significant up-regulation of PARP1, and PARP inhibitors significantly delay tumor growth and metastatic colonization and reverse neuroendocrine features in Trop2-driven NEPC. Our findings establish Trop2 as a driver and therapeutic target for metastatic prostate cancer with neuroendocrine phenotype and suggest that high Trop2 levels could identify cancers that are sensitive to Trop2-targeting therapies and PARP1 inhibition.

    View details for DOI 10.1073/pnas.1905384117

    View details for PubMedID 31932422

  • I-125-Tetrazines and Inverse-Electron-Demand Diels-Alder Chemistry: A Convenient Radioiodination Strategy for Biomolecule Labeling, Screening, and Biodistribution Studies BIOCONJUGATE CHEMISTRY Albu, S. A., Al-Karmi, S. A., Vito, A., Dzandzi, J. P., Zlitni, A., Beckford-Vera, D., Blacker, M., Janzen, N., Patel, R. M., Capretta, A., Valliant, J. F. 2016; 27 (1): 207-216

    Abstract

    A convenient method to prepare radioiodinated tetrazines was developed, such that a bioorthogonal inverse electron demand Diels-Alder reaction can be used to label biomolecules with iodine-125 for in vitro screening and in vivo biodistribution studies. The tetrazine was prepared by employing a high-yielding oxidative halo destannylation reaction that concomitantly oxidized the dihydrotetrazine precursor. The product reacts quickly and efficiently with trans-cyclooctene derivatives. Utility was demonstrated through antibody and hormone labeling experiments and by evaluating products using standard analytical methods, in vitro assays, and quantitative biodistribution studies where the latter was performed in direct comparison to Bolton-Hunter and direct iodination methods. The approach described provides a convenient and advantageous alternative to conventional protein iodination methods that can expedite preclinical development and evaluation of biotherapeutics.

    View details for DOI 10.1021/acs.bioconjchem.5b00609

    View details for Web of Science ID 000368651600023

    View details for PubMedID 26699913

  • Synthesis, characterization and radiolabeling of carborane-functionalized tetrazines for use in inverse electron demand Diels-Alder ligation reactions JOURNAL OF ORGANOMETALLIC CHEMISTRY Genady, A. R., Tan, J., El-Zaria, M. E., Zlitni, A., Janzen, N., Valliant, J. F. 2015; 791: 204-213
  • The synthesis, magnetic purification and evaluation of Tc-99m-labeled microbubbles NUCLEAR MEDICINE AND BIOLOGY Lazarova, N., Causey, P. W., Lemon, J. A., Czorny, S. K., Forbes, J. R., Zlitni, A., Genady, A., Foster, F. S., Valliant, J. F. 2011; 38 (8): 1111-1118

    Abstract

    Ultrasound (US) contrast agents based on microbubbles (MBs) are being investigated as platforms for drug and gene delivery. A methodology for determining the distribution and fate of modified MBs quantitatively in vivo can be achieved by tagging MBs directly with (99m)Tc. This creates the opportunity to employ dual-modality imaging using both US and small animal SPECT along with quantitative ex vivo tissue counting to evaluate novel MB constructs.A (99m)Tc-labeled biotin derivative ((99m)TcL1) was prepared and incubated with streptavidin-coated MBs. The (99m)Tc-labeled bubbles were isolated using a streptavidin-coated magnetic-bead purification strategy that did not disrupt the MBs. A small animal scintigraphic/CT imaging study as well as a quantitative biodistribution study was completed using (99m)TcL1 and (99m)Tc-labeled bubbles in healthy C57Bl-6 mice.The imaging and biodistribution data showed rapid accumulation and retention of (99m)Tc-MBs in the liver (68.2±6.6 %ID/g at 4 min; 93.3±3.2 %ID/g at 60 min) and spleen (214.2±19.7 %ID/g at 4 min; 213.4±19.7 %ID/g at 60 min). In contrast, (99m)TcL1 accumulated in multiple organs including the small intestine (22.5±3.6 %ID/g at 4 min; 83.4±5.9 %ID/g at 60 min) and bladder (184.0±88.1 %ID/g at 4 min; 24.2±17.7 %ID/g at 60 min).A convenient means to radiolabel and purify MBs was developed and the distribution of the labeled products determined. The result is a platform which can be used to assess the pharmacokinetics and fate of novel MB constructs both regionally using US and throughout the entire subject in a quantitative manner by employing small animal SPECT and tissue counting.

    View details for DOI 10.1016/j.nucmedbio.2011.04.008

    View details for Web of Science ID 000298070400005

    View details for PubMedID 21741260