Bio


•---Clinical Imaging Book Co-Author: The PET Method: Tracer Principle and Radiochemistry
•---Nuclear Medicine Scientist (Specialization: Drug Design & PET/CT/SPECT Imaging)
•---Clinical Radiopharmaceuticals Expert (cGMP Compliance : Production, QA/QC, IND)
•---International Peace Ambassador for Canada and USA, GLPC, since Nov 2021
•---Business Strategist (Founder & CEO of Scientudio Inc. platform for professionals/students in life sciences since Sept, 2021)
•---Public Affairs Strategist (Former executive Director of Public Affairs, GIANT, with WHO-UN, May 2021-April, 2022)
•---Founder of Endorse Hope (Vocational trainings, science education, women's health, children welfare in African/Asian countries; since Feb. 2022)
•---Former Chair of SCWIST Science Symposium, 2021 (National Competition for Young Scientists in Canada) (Former Director of Communications & Events (SCWIST, 2021)


List of Publications:
https://www.scopus.com/authid/detail.uri?authorId=35190681600

Current Role at Stanford


Research Scientist
CRF, MIPS, Stanford School of Medicine, Stanford | January 2022 — Present

Responsibilities:
• R & D of radiopharmaceuticals for oncology and neuroscience
• Market strategic report for theragnostic-isotopes for Nextgen Cyclotron project
• CRF website development project
https://cyclotron.stanford.edu/

Supervisors


Education & Certifications


  • Certified, University of British Columbia, CIRTL Associate - Instructional Skills (2020)
  • Certified, Harvard Business School Online, Sustainable Business Strategy (2020)
  • Certified, Harvard Business School Online, Business Analytics (2020)
  • PhD, Eberhard-Karls University, Tuebingen, Radiochemistry/Biochemistry (2011)

Professional Affiliations and Activities


  • Member, Stanford Venture Studio (2022 - Present)
  • Member, Society of Nuclear Medicine and Molecular Imaging (2012 - Present)
  • Member, WMIS World Molecular Imaging Society (2016 - Present)
  • Member, WiN (Women in Nuclear) Canada (2019 - Present)
  • Member, Women in Radiopharmaceuticals, IAEA (2022 - Present)
  • Executive Director of Public Affairs, GIANT (Global Immunization Action Networking Team, with WHO-UN) (https://www.giant-int.org/about/) (2021 - 2022)
  • Founder & CEO, Scientudio Inc. https://www.scientudio.biz/ (2021 - Present)
  • Founder, Endorse Hope (Not-for-Profit) https://www.endorse-hope.org/ (2022 - Present)

All Publications


  • Development and biological evaluation of[F-18]FMN3PA & [F-18] FMN3PU for leucine-rich repeat kinase 2 (LRRK2) in vivo PET imaging EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY Malik, N., Kornelsen, R., McCormick, S., Colpo, N., Merkens, H., Bendre, S., Benard, F., Sossi, V., Schirrmacher, R., Schaffer, P. 2021; 211: 113005

    Abstract

    Among all genetic mutations of LRRK2, the G2019S mutation is the most commonly associated with the late-onset of Parkinson's disease (PD). Hence, one potential therapeutic approach is to block the hyperactivity of mutated LRRK2 induced by kinase inhibition. To date, only a few LRRK2 kinase inhibitors have been tested for in vivo quantification of target engagement by positron emission tomography (PET). In this study, we performed biological evaluations of two radiolabeled kinase inhibitors i.e. [18F]FMN3PA (14) and [18F]FMN3PU for LRRK2 (15).Radiosyntheses of [18F]FMN3PA (14) and [18F]FMN3PU (15) were performed using K[18F]-F-K222 complex in a TRACERlab FXN module and purification was carried out via C18 plus (Sep-Pak) cartridges. In vitro specific binding assays were performed in rat brain striatum and kidney tissues using GNE-0877 as a blocking agent (Ki = 0.7 nM). For in vivo blocking, 3 mg/kg of GNE-0877 was injected 30 min before radiotracer injection via tail vein in wild-type (WT) mice (n = 4). Dynamic scans by PET/CT (Siemens Inveon) were performed in WT mice (n = 3).Radiofluorinations resulted in radiochemical yields (RCYs) of 25 ± 1.3% (n = 6) ([18F]FMN3PU, 15) and 37 ± 1.6% (n = 6) ([18F]FMN3PA, 14) with ≥96% radiochemical purity (RCP) and a molar activity (MA) of 3.55 ± 1.6 Ci/μmol (131 ± 56 GBq/μmol) for [18F]FMN3PU (15) and 4.57 ± 1.7 Ci/μmol (169 ± 63 GBq/μmol) for [18F]FMN3PA (14), respectively. Saturation assays showed high specific binding for rat brain striatum with Kd 20 ± 1.3 nM ([18F]FMN3PA, 14) and 23.6 ± 4.0 nM ([18F]FMN3PU, 15). In vivo blocking data for [18F]FMN3PA (14) was significant for brain (p < 0.0001, 77% blocking) and kidney (p = 0.0041, 65% blocking). PET images showed uptake in mouse brain striatum.In the presence of GNE-0877 as a blocking agent, the specific binding of [18F]FMN3PA (14) and [18F]FMN3PU (15) was significant in vitro. [18F]FMN3PA (14) showed good brain uptake in vivo, though fast clearance from brain was observed (within 10-15 min).

    View details for DOI 10.1016/j.ejmech.2020.113005

    View details for Web of Science ID 000639375500007

    View details for PubMedID 33248850

  • Lewis Acid-Facilitated Radiofluorination of MN3PU: A LRRK2 Radiotracer MOLECULES Malik, N., Bendre, S., Schirrmacher, R., Schaffer, P. 2020; 25 (20)

    Abstract

    Temperature-sensitive radiopharmaceutical precursors require lower reaction temperatures (<100 °C) during nucleophilic radiofluorination in order to avoid compound thermolysis, often resulting in sub-optimal radiochemical yields (RCYs). To facilitate nucleophilic aromatic substitution (SNAr) of nucleofuges commonly used in radiofluorination (e.g., nitro group), we explored the use of Lewis acids as nucleophilic activators to accelerate [18F]fluoride incorporation at lower temperatures, and thereby increasing RCYs for thermolabile activated precursors. Lewis acid-assisted radiofluorination was exemplified on the temperature-sensitive compound 1-(4-(4-morpholino-7-neopentyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)phenyl)-3-(6-nitropyridin-3-yl)urea (MN3PU, compound 3) targeting leucine-rich repeat kinase 2 (LRRK2), an important target in the study of Parkinson's disease and various cancers.To a vessel containing dried K[18F]F-K222 complex, a solution of precursor MN3PU ((3), 1 mg; 1.8 μmol) and Lewis acid (6 μL of 0.2 μmol: chromium II chloride (A), ferric nitrite (B) or titanocene dichloride (C)) in 500 μL of N,N-dimethylformamide (DMF) (with 10% t-BuOH for B) were added. Reactions were stirred for 25 min at 90 °C. In parallel, reactions were conducted without the addition of Lewis acids for baseline comparison. After purification via preconditioned Sep-Pak C18 plus cartridges, aliquots were analyzed by analytical radio-HPLC.Non-decay corrected radiochemical yields (ndc RCYs) for [18F]FMN3PU (7) were improved from 1.7 ± 0.7% (no addition of Lewis acids) to 41 ± 1% using Cr(II) and 37 ± 0.7% using Ti(II)-based Lewis acids, with radiochemical purities of ≥96% and molar activities (Am) of up to 3.23 ± 1.7 Ci/μmol (120 ± 1.7 GBq/μmol).RCYs of [18F]FMN3PU (7) improved from ~5% using conventional nucleophilic radiofluorination, up to 41 ± 1% using Lewis-acid supported SNAr.

    View details for DOI 10.3390/molecules25204710

    View details for Web of Science ID 000585646100001

    View details for PubMedID 33066671

    View details for PubMedCentralID PMC7587332

  • Electrostatic Effects Accelerate Decatungstate-Catalyzed C-H Fluorination Using [F-18]- and [F-19]NFSI in Small Molecules and Peptide Mimics ACS CATALYSIS Yuan, Z., Yang, H., Malik, N., Colovic, M., Weber, D. S., Wilson, D., Benard, F., Martin, R. E., Warren, J. J., Schaffer, P., Britton, R. 2019; 9 (9): 8276-8284
  • PET imaging study of brown adipose tissue (BAT) activity in mice devoid of receptor for advanced glycation end products (RAGE). Journal of biosciences Ding, Y., Malik, N., Mendoza, S., Tuchman, D., Del Pozo, C. H., Diez, R. L., Schmidt, A. 2019; 44 (4)

    Abstract

    Brown adipose tissue (BAT) is responsible for adaptive thermogenesis. We previously showed that genetic deficiency of receptor for advanced glycation end products (RAGE) prevented the effects of high-fat diet (HFD). This study was to compare BAT activity in RAGE knock out (Ager-/-, RKO) and wild-type (WT) mice after treated with HFD or LFD. [18F]FDG PET-CT imaging under identical cold-stimulated conditions and mean standard uptake values (SUVmean), ratio of SUViBAT/SUVmuscle (SUVR, muscle as the reference region) and percentage ID/g were used for BAT quantification. The results showed that [18F]FDG uptake (e.g., SUVR) in WT-HFD mice was significantly reduced (three-fold) as compared to that in WT-LFD (1.40 +/- 0.07 and 4.03 +/- 0.38; P = 0.004). In contrast, BAT activity in RKO mice was not significantly affected by HFD, with SUVRRKO-LFD: 2.14 +/- 0.10 and SUVRRKO-LFD: 1.52 +/- 0.13 (P = 0.3). The uptake in WT-LFD was almost double of that in RKO-LFD (P = 0.004); however, there was no significant difference between RKO-HFD and WT-HFD mice (P = 0.3). These results, corroborating our previous findings on the measurement of mRNA transcripts for UCP1 in the BAT, suggest that RAGE may contribute to altered energy expenditure and provide a protective effect against HFD by Ager deletion (Ager -/-).

    View details for PubMedID 31502571

  • PET imaging study of brown adipose tissue (BAT) activity in mice devoid of receptor for advanced glycation end products (RAGE) JOURNAL OF BIOSCIENCES Ding, Y., Malik, N., Mendoza, S., Tuchman, D., Del Pozo, C., Diez, R., Schmidt, A. 2019; 44 (4)
  • F-18-Branched-Chain Amino Acids: Structure-Activity Relationships and PET Imaging Potential JOURNAL OF NUCLEAR MEDICINE Nodwell, M. B., Yang, H., Merkens, H., Malik, N., Colovic, M., Wagner, B., Martin, R. E., Benard, F., Schaffer, P., Britton, R. 2019; 60 (7): 1003-1009

    Abstract

    The large, neutral L-type amino acid transporters (LAT1-LAT4) are sodium-independent transporters that are widely distributed throughout the body. LAT expression levels are increased in many types of cancer, and their expression increases as cancers progress, leading to high expression levels in high-grade tumors and metastases. Because of the key role and overexpression of LAT in many types of cancer, radiolabeled LAT substrates are promising candidates for nuclear imaging of malignancies that are not well revealed by conventional radiotracers. The goal of this study was to examine the structure-activity relationships of a series of 18F-labeled amino acids that were predicted to be substrates of the LAT transport system. Methods: Using a photocatalytic radical fluorination, we prepared a series of 11 fluorinated branched-chain amino acids and evaluated them and their nonfluorinated parents in a cell-based LAT affinity assay. We radiofluorinated selected branched-chain amino acids via the same radical fluorination reaction and evaluated tumor uptake in U-87 glioma xenograft-bearing mice. Results: Structure-activity relationship trends observed in a LAT affinity assay were maintained in further in vitro studies, as well as in vivo using a U-87 xenograft model. LAT1 uptake was tolerant of fluorinated amino acid stereochemistry and chain length. PET imaging and biodistribution studies showed that the tracer (S)-5-18F-fluorohomoleucine had rapid tumor uptake, favorable in vivo kinetics, and good stability. Conclusion: By using an in vitro affinity assay, we could predict LAT-mediated cancer cell uptake in a panel of fluorinated amino acids. These predictions were consistent when applied to different cell lines and murine tumor models, and several new tracers may be suitable for further development as oncologic PET imaging agents.

    View details for DOI 10.2967/jnumed.118.220483

    View details for Web of Science ID 000473327300040

    View details for PubMedID 30683769

    View details for PubMedCentralID PMC6604688

  • Site-Selective, Late-Stage C-H F-18-Fluorination on Unprotected Peptides for Positron Emission Tomography Imaging ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Yuan, Z., Nodwell, M. B., Yang, H., Malik, N., Merkens, H., Benard, F., Martin, R. E., Schaffer, P., Britton, R. 2018; 57 (39): 12733-12736

    Abstract

    Peptides are often ideal ligands for diagnostic molecular imaging due to their ease of synthesis and tuneable targeting properties. However, labelling unmodified peptides with 18 F for positron emission tomography (PET) imaging presents a number of challenges. Here we show the combination of photoactivated sodium decatungstate and [18 F]-N-fluorobenzenesulfonimide effects site-selective 18 F-fluorination at the branched position in leucine residues in unprotected and unaltered peptides. This streamlined process provides a means to directly convert native peptides into PET imaging agents under mild aqueous conditions, enabling rapid discovery and development of peptide-based molecular imaging tools.

    View details for DOI 10.1002/anie.201806966

    View details for Web of Science ID 000444941600019

    View details for PubMedID 30086209

  • Co-occurrence of aflatoxins and ochratoxin A in nuts, dry fruits, and nuty products JOURNAL OF FOOD SAFETY Iqbal, S., Mehmood, Z., Asi, M., Shahid, M., Sehar, M., Malik, N. 2018; 38 (4)

    View details for DOI 10.1111/jfs.12462

    View details for Web of Science ID 000441887600006

  • Development of Novel Radioligands for Imaging LRRK2 in Parkinson's Disease Malik, N., Tuchman, D., Sandell, J., Gifford, A., Ding, Y. SOC NUCLEAR MEDICINE INC. 2018
  • Heavy Metals in Selected Vegetables from Markets of Faisalabad, Pakistan JOURNAL OF FOOD PROTECTION Iqbal, S., Ullah, Z., Asi, M. R., Jinap, S., Ahmad, M., Sultan, M., Malik, N. 2018; 81 (5): 806-809

    Abstract

    Two hundred ten samples of selected vegetables (okra, pumpkin, tomato, potato, eggplant, spinach, and cabbage) from Faisalabad, Pakistan, were analyzed for the analysis of heavy metals: cadmium (Cd), lead (Pb), arsenic (As), and mercury (Hg). Inductively coupled plasma optical emission spectrometry was used for the analysis of heavy metals. The mean levels of Cd, Pb, As, and Hg were 0.24, 2.23, 0.58, and 7.98 mg/kg, respectively. The samples with Cd (27%), Pb (50%), and Hg (63%) exceeded the maximum residual levels set by the European Commission. The mean levels of heavy metals found in the current study are high and may pose significant health concerns for consumers. Furthermore, considerable attention should be paid to implement comprehensive monitoring and regulations.

    View details for DOI 10.4315/0362-028X.JFP-17-256

    View details for Web of Science ID 000443096600015

    View details for PubMedID 29637809

  • Natural occurrence of patulin in different fruits, juices and smoothies and evaluation of dietary intake in Punjab, Pakistan FOOD CONTROL Iqbal, S., Malik, S., Asi, M., Selamat, J., Malik, N. 2018; 84: 370-374
  • Survey of mycotoxins in retail market cereals, derived products and evaluation of their dietary intake FOOD CONTROL Alim, M., Iqbal, S., Mehmood, Z., Asi, M., Zikar, H., Chanda, H., Malik, N. 2018; 84: 471-477
  • Synthesis and In Vitro and In Vivo Evaluation of [H-3]LRRK2-IN-1 as a Novel Radioligand for LRRK2 MOLECULAR IMAGING AND BIOLOGY Malik, N., Gifford, A. N., Sandell, J., Tuchman, D., Ding, Y. 2017; 19 (6): 837-845

    Abstract

    LRRK2 (leucine-rich repeat kinase 2) has recently been proven to be a promising drug target for Parkinson's disease (PD) due to an apparent enhanced activity caused by mutations associated with familial PD. To date, there have been no reports in which a LRRK2 inhibitor has been radiolabeled and used for in in vitro or in vivo studies of LRRK2. In the present study, we radiolabeled the LRRK2 ligand, LRRK-IN-1, for the purposes of performing in vitro (IC50, K d , B max, autoradiography) and in vivo (biodistribution, and blocking experiments) evaluations in rodents and human striatum tissues.[3H]LRRK2-IN-1 was prepared with high radiochemical purity (>99 %) and a specific activity of 41 Ci/mmol via tritium/hydrogen (T/H) exchange using Crabtree's catalyst. For IC50, K d , and B max determination, LRRK2-IN-1 was used as a competing drug for nonspecific binding assessment. The specific binding of the tracer was further evaluated via an in vivo blocking study in mice with a potent LRRK2 inhibitor, Pf-06447475.In vitro binding studies demonstrated a saturable binding site for [3H]LRRK2-IN-1 in rat kidney, rat brain striatum and human brain striatum with K d of 26 ± 3 and 43 ± 8, 48 ± 2 nM, respectively. In rat, the density of LRRK2 binding sites (B max) was higher in kidney (6.4 ± 0.04 pmol/mg) than in brain (2.5 ± 0.03 pmol/mg), however, in human brain striatum, the B max was 0.73 ± 0.01 pmol/mg protein. Autoradiography imaging in striatum of rat and human brain tissues gave results consistent with binding studies. In in vivo biodistribution and blocking studies in mice, co-administration with Pf-06447475 (10 mg/kg) reduced the uptake of [3H]LRRK2-IN-1 (%ID/g) by 50-60% in the kidney or brain.The high LRRK2 brain density observed in our study suggests the feasibility for positron emission tomography imaging of LRRK2 (a potential target) with radioligands of higher affinity and specificity.

    View details for DOI 10.1007/s11307-017-1070-1

    View details for Web of Science ID 000414209700005

    View details for PubMedID 28289968

    View details for PubMedCentralID PMC5597475

  • Synthesis and In Vitro and In Vivo Evaluation of [H-3]LRRK2-IN-1 as a Novel Radioligand for LRRK2 (vol 19, pg 837, 2017) MOLECULAR IMAGING AND BIOLOGY Malik, N., Gifford, A. N., Sandell, J., Tuchman, D., Ding, Y. 2017; 19 (6): 846

    View details for DOI 10.1007/s11307-017-1086-6

    View details for Web of Science ID 000414209700006

    View details for PubMedID 28462461

  • Synthesis and In Vitro and In Vivo Evaluation of Novel Radioligands for LRRK2 Ding, Y., Malik, N., Tuchman, D., Sandell, J., Gifford, A. NATURE PUBLISHING GROUP. 2017: S579-S580
  • Survey of aflatoxins and ochratoxin A in retail market chilies and chili sauce samples FOOD CONTROL Iqbal, S., Asi, M., Mehmood, Z., Mumtaz, A., Malik, N. 2017; 81: 218-223
  • The seasonal variation of aflatoxin M-1 in milk and dairy products and assessment of dietary intake in Punjab, Pakistan FOOD CONTROL Iqbal, S., Asi, M., Malik, N. 2017; 79: 292-296
  • Synthesis and evaluation of [H-3]LRRK2-IN-1 as a novel radioligand for in vitro and in vivo studies on LRRK2 Malik, N., Gifford, A., Sandell, J., Tuchman, D., Ding, Y. WILEY. 2017: S40-S41
  • Synthesis and in vitro and in vivo evaluation of a novel radioligand for LRRK2 Malik, N., Tuchman, D., Sandell, J., Gifford, A., Ding, Y. SOC NUCLEAR MEDICINE INC. 2017
  • Effects of high-fat diet on brown adipose tissue (BAT) activity in wild type vs. RAGE null mice Malik, N., del Pozo, C., Song, F., Mendoza, S., Tuchman, D., Schmidt, A., Ding, Y. SOC NUCLEAR MEDICINE INC. 2017
  • PET study of Brown Adipose Tissue (BAT) Activity in Mice Devoid of Receptor for Advanced Glycation End Product (RAGE) Malik, N., Mendoza, S., Tuchman, D., Del Pozo, C., Diez, R., Schmidt, A., Ding, Y. WILEY. 2017: S536
  • Processing Techniques of Algae-Based Materials ALGAE BASED POLYMERS, BLENDS, AND COMPOSITES: CHEMISTRY, BIOTECHNOLOGY AND MATERIALS SCIENCES Iqbal, S. Z., Fazal-ur-Rehman, Malik, N., Rehman, K., Asi, M. R., Zia, K. M., Zuber, M., Ali, M. 2017: 671-686
  • A Limited Survey of Aflatoxins and Zearalenone in Feed and Feed Ingredients from Pakistan JOURNAL OF FOOD PROTECTION Iqbal, S., Asi, M., Nisar, S., Zia, K., Jinap, S., Malik, N. 2016; 79 (10): 1798-1801

    Abstract

    This work presents current information on the presence of aflatoxins (AFs) and zearalenone (ZEN) in feed and feed ingredients from Punjab, Pakistan. The 105 samples tested were concentrated feed, i.e., cotton seed meal (18 samples) and soybean meal (14), and feed ingredients, i.e., crushed corn (17), crushed wheat (15), barley (17). and poultry feed (24). Samples were analyzed using high-performance liquid chromatography equipped with a fluorescence detector. Analysis revealed that 69 of 105 samples were contaminated with AFs, and the highest mean concentrations of AFB1 (6.20 μg/kg) and total AFs (9.30 μg/kg) were found in poultry feed samples. The mean total AF concentrations ranged from the limit of quantification to 165.5 μg/kg. However, 75 of the 105 samples were positive for ZEN. The highest mean concentration (19.45 μg/kg) was found in poultry feed samples. The mean ZEN concentrations were 0.15 to 145.30 μg/kg. The prevalence of AFs and ZEN was high in feed and feed ingredients and needs urgent attention.

    View details for DOI 10.4315/0362-028X.JFP-16-091

    View details for Web of Science ID 000384963800020

    View details for PubMedID 28221839

  • Radiofluorination of PSMA-HBED via (AlF2+)-F-18 Chelation and Biological Evaluations In Vitro MOLECULAR IMAGING AND BIOLOGY Malik, N., Baur, B., Winter, G., Reske, S. N., Beer, A. J., Solbach, C. 2015; 17 (6): 777-785

    Abstract

    Ga-68-labeled prostate-specific membrane antigen (PSMA) ligands have been used clinically for positron emission tomography (PET) imaging of prostate cancer. However, F-18-labeled compounds offer several advantages, including the potential for delayed imaging, high starting activities enabling multidose preparation, and improved spatial resolution in PET. For F-18 labeling of peptides conjugated with a suitable chelator, a fast and feasible method is the use of [Al(18)F](2+). In the present study, the radiofluorinations of a well-known PSMA ligand Glu-NH-CO-NH-Lys(Ahx)-HBED-CC (PSMA-HBED) via [Al(18)F](2+) were performed with respect to various reaction parameters, along with the biological evaluations in a cell experiment.[Al(18)F]PSMA-HBED was prepared by adding Na[(18)F]F into a vial containing 0.026 μmol peptide (in 0.05 M NaOAc buffer) and 0.03 μmol AlCl3⋅6H2O (in 0.05 M NaOAc buffer). Then, it was stirred at different temperatures from 1 to 30 min. Afterwards, purification was carried out by solid phase extraction. Biological evaluations were performed in PSMA-positive cell lines LNCaP C4-2, along with a negative control using PC-3 cell lines.The best labeling results (81 ± 0.5 %, n = 4) were observed with 0.026 μmol peptide (30 °C, 5 min). For preclinical experiments, the production of [Al(18)F]PSMA-HBED at 35 °C including purification by solid phase extraction (SPE) succeeded within 45 min, resulting in a radiochemical yield of 49 ± 1.2 % (decay-corrected, n = 6, radiochemical purity ≥98 %) at EOS. The labeled peptide revealed serum stability for 4 h as well as a promising binding coefficient (K D) value of 10.3 ± 2.2 nM in cell experiments with PSMA-positive LNCaP C4-2 cells.An efficient and one-pot method for the radiosynthesis of [Al(18)F]PSMA-HBED was developed (0.26 μmol of precursor at 35 °C). In cell culture studies, the K D suggests [Al(18)F]PSMA-HBED as a potential PSMA ligand for future investigations in vivo and clinical applications afterwards.

    View details for DOI 10.1007/s11307-015-0844-6

    View details for Web of Science ID 000364941700006

    View details for PubMedID 25869080

  • Biodistribution and delivery efficiency of unmodified tumor-derived exosomes JOURNAL OF CONTROLLED RELEASE Smyth, T., Kullberg, M., Malik, N., Smith-Jones, P., Graner, M. W., Anchordoquy, T. J. 2015; 199: 145-155

    Abstract

    The use of exosomes as a drug delivery vehicle has gained considerable interest. To establish if exosomes could be utilized effectively for drug delivery, a better understanding of their in vivo fate must be established. Through comparisons to liposomal formulations, which have been studied extensively for the last thirty years, we were able to make some comprehensive conclusions about the fate of unmodified tumor-derived exosomes in vivo. We observed a comparable rapid clearance and minimal tumor accumulation of intravenously-injected exosomes, PC:Chol liposomes, and liposomes formulated with the lipid extract of exosomes, suggesting that the unique protein and lipid composition of exosomes does not appreciably impact exosomes' rate of clearance and biodistribution. This rapid clearance along with minimal tumor accumulation of unmodified exosomes limits their use as an anti-cancer drug delivery vehicle; however, when delivered intratumorally, exosomes remained associated with tumor tissue to a significantly greater extent than PC:Chol liposomes. Furthermore, experiments utilizing mice with impaired adaptive or innate immune systems, revealed the significance of the innate immune system along with the complement protein C5 on exosomes' rate of clearance.

    View details for DOI 10.1016/j.jconrel.2014.12.013

    View details for Web of Science ID 000348456800016

    View details for PubMedID 25523519

    View details for PubMedCentralID PMC4441346

  • Synthesis of O-[2-[F-18]fluoro-3-(2-nitro-1H-imidazole-1-yl)propyl]tyrosine ([F-18]FNT]) as a new class of tracer for imaging hypoxia JOURNAL OF RADIOANALYTICAL AND NUCLEAR CHEMISTRY Malik, N., Lin, X., Loeffler, D., Shen, B., Solbach, C., Reischl, G., Voelter, W., Machulla, H. 2012; 292 (3): 1025-1033
  • Radiosynthesis of a new PSMA targeting ligand ([F-18]FPy-DUPA-Pep) APPLIED RADIATION AND ISOTOPES Malik, N., Machulla, H., Solbach, C., Winter, G., Reske, S. N., Zlatopolskiy, B. 2011; 69 (7): 1014-1018

    Abstract

    Due to the specificity of expression of PSMA (prostate specific membrane antigen) particularly in prostate cancer cells (e.g. LNCaP), numerous PSMA ligands have been synthesized until now. In the current study, we synthesized DUPA-Pep having 2-[3-(1,3-dicarboxypropyl)ureido]pentanedioic acid (DUPA) linked via 8-aminooctanoic acid to two phenylalanine residues and chose 6-[(18)F]fluoronicotinic acid 2,3,5,6-tetrafluorophenyl ester [(18)F]FPy-TFP as a prosthetic group for coupling. [(18)F]FPy-DUPA-Pep was obtained in a radiochemical yield of 48±0.9% (decay uncorrected) within 50 min with a chemical purity of >98%.

    View details for DOI 10.1016/j.apradiso.2011.03.041

    View details for Web of Science ID 000291456300018

    View details for PubMedID 21498081

  • A novel approach for imaging hypoxia: Tyrosine coupled with 2-nitroimidazole ([18F]FNT]) Malik, N., Lin, X., Loffler, D., Shen, B., Solbach, C., Reischl, G., Machulla, H. SOC NUCLEAR MEDICINE INC. 2011