Rolf Swenson

Rolf Swenson, Ph.D.

Director
301-827-1741

Biography

Rolf Swenson received his Ph.D. in synthetic organic chemistry at Cornell University working with Professor John McMurry.  After post-doctoral study with Professor Wolfgang Oppolzer at the University of Geneva Switzerland, and Professor Hector DeLuca at the University of Wisconsin Madison, he joined Abbott Laboratories as a medicinal chemist. He moved to the combinatorial chemistry group and was a group leader working on rapid parallel synthesis. He then moved to Orchid BioSciences as a Director of Chemistry in charge of combinatorial chemistry in microfluidic devices, and while there led a project team that automated SNP genotyping to perform 1,000,000 genotypes/day. He left Orchid to become the International Area Head for Discovery Chemistry at Bracco Research USA. He led a team that prepared diagnostic imaging agents for PET/SPECT, Contrast enhanced ultrasound, MRI and optical applications.  When the Princeton research facility was closed, Dr. Swenson started Arroyo BioSciences, LLC, which focused on discovering new drugs for the treatment of idiopathic pulmonary fibrosis and other fibrotic disease. Since the beginning of 2014, Dr. Swenson has been the Director of the Imaging Probe Development Center, where he has managed a group of chemists who prepare chemical tools including diverse diagnostic probes for the intramural community. He is an inventor on 65 US patents and an author on 52 scientific papers. He has contributed to one approved drug and five other compounds advanced to clinical trials. 

Research

Research
- Rolf Swenson, Ph.D.

Learn more about requesting scientific collaboration with IPDC.

Key offerings for diverse modality imaging: 

  • Fluorescent/Optical Imaging
  • Targeting Groups
  • MRI Imaging
  • PET & SPECT Imaging
This ven diagram graphically represents the offerings of the Chemistry and Synthesis Center.

Fluorescent/Optical Imaging (Fluorescent/optical and multiple dyes)

Fluorescent

Fluorescent/Optical Imaging - Antibody

 

Fluorescent/Optical Imaging - Fluorescent

 

 

Fluorescent/Optical Imaging – Antibody

 

In vivo fluorescence lifetime imaging monitors bindingof specific probes to cancer biomarkers

Role of Fluorophore Charge on the In Vivo Optical Imaging Properties of Near-Infrared Cyanine Dye/Monoclonal Antibody Conjugates

Targeting Groups: (Small Molecules, Peptides and Antibodies/Proteins)

Small Molecules

Peptides

 

Targeting - small molecule

 

 

Targeting Groups - Peptides

 

Automatedsynthesisof[18F](2S,4R)-4-fluoroglutamine on aGETRACERlabTM FX-NPromodule

STAQ: A route toward low power, multicolor nanoscopy

MRI Imaging (Hyperpolarized*, Dendrimer, Iron Oxide Nanoparticles)

Dendrimers

Iron Oxide Nanoparticles

 

MRI Imaging - Dendrimer

 

 

MRI Imaging - Iron Oxide Nanoparticles

 

Preparation and long-term biodistribution studies of a PAMAM dendrimer G5-Gd-BnDOTA

Synthesis of Ultrasmall Superparamagnetic Iron Oxide Nanoparticles for fMRI

PET & SPECT Imaging (18F, 125I, and 89Zr)

18F - Protein

125I

89Zr

 

PET & SPECT Imaging - 18F Protein

 

 

PET & SPECT Imaging - 125I

 

 

PET & SPECT Imaging - 89Zr

 

Synthesis of fluorine-18 radio-labeled serum albumins for PET blood pool imaging

Synthesis and Pharmacological Characterization of [125I] MRS1898, a High Affinity, Selective Radioligand for the Rat A3 Adenosine Receptor

89Zr-Oxine Complex PET Cell Imaging in Monitoring Cell based Therapies

18F Favipiravir 18F Albumin
favipiravir diagram albumin diagram

Synthesis of [18F]Favipiravir and Biodistribution in C3H/HeN Mice as Assessed by Positron Emission Tomography.

One-pot synthesis and bio-distribution of fluorine-18 serum albumin for vascular imaging.

    New Offerings
    - Rolf Swenson, Ph.D.

    1. PROTACS (Proteolysis-targeting chimeras)
    2. Metabolomic feature identification
    3. Fragment based lead optimization by NMR
    4. Targeted nanoparticles (Fe, Au, C)
    5. Peptide optimization and multimerization
    6. Small Molecule Synthesis

    I. PROTACS - Proteolysis-targeting chimeras (PROTACS) are a small molecule based approach to knocking out a specific protein.  Similar to siRNA or CRISPR-Cas9, a PROTAC can degrade a target protein via the native proteasomal machinery, without genetic modification to the cell. CSC works with PIs to collaboratively design and synthesize PROTACS to degrade specific proteins of interest.

    II. Metabolomic feature identification - The presence and amount of a specific metabolite in cells, biofluids, tissues, or organisms can be directly reflective of biochemical processes occurring in a biological system in response to its environment.  In a typical untargeted metabolomics experiment, hundreds to thousands of features are identified by HPLC or GC retention time – MS m/z pairs (features).  The CSC can identify putative features and confirm by preparing noncommercially available authentic standards (and labeled analogs).  We don’t perform the metabolism studies.

    III. Fragment based lead optimization by NMR - Structure-activity relationships (SAR) can be explored by NMR (“SAR by NMR”).  Often small organic molecules (fragments) are found to bind at proximal subsites of the protein. Once these fragments are identified the CSC can optimize, and link the fragments to generate a new single molecule that takes advantage of both binding sites. Two fragments with individual micromolar affinities can be tethered to produce a compound with the nanomolar affinity.

    IV. Targeted nanoparticles (Fe, Au, C) - Targeted nanoparticles have multiple uses in fluorescent and MRI imaging. The ability to manipulate the tissue uptake and biodistribution of these moieties relies on a highly tailorable and fully accessible surface.  The introduction of various functional groups can be used to solubilize, reduce aggregation, and attach drugs or biomolecules to the nanoparticle.  The CSC has prepared targeted Fe and Au nanoparticles as well as fluorescent nanodiamonds.

    V. Peptide optimization and multimerization - We have expertise in peptide design, and use solid phase peptide synthesis (SPPS) to investigate SAR of sequences of interest to increase potency, metabolic stability, and water solubility.  We can synthesize multimers to increase potency based on avidity.  In addition, we also offer solution phase synthesis of complex peptides where SPPS is not effective.  We have experience in derivatization of peptides with reporter moieties, e.g. dyes, macrocycles for chelation and precursors for radiolabeling.

    VI. Small Molecule Synthesis - Medicinal chemistry leads and potential drugs from the literature are widely used as chemical tools for studying biological functions. We routinely synthesize compounds from the literature, perform hit to lead optimization for screening efforts, and derivatize heterocycles with fluorescent or Raman tags or chelates.

     

      Other Offerings
      - Rolf Swenson, Ph.D.

      1. Fluorescent probes
      2. Hyperpolarized probes for MRI
      3. Lanthanide chelates for MRI
      4. 89Zr and 18F PET probes
      5. Liposomes, protein purification, and antibody digestion

      I. Fluorescent probes - Fluorescence remains the premier approach to monitoring occurrences on a cellular level, with approaches that grow ever more sophisticated. CSC synthesizes custom fluorescent and light-activated probes, including fluorophore-labeled peptides, fluorescent or photoactivated drugs, fluorescent versions of native biological small molecules, and other literature-reported fluorescent tools, for biological research.

      II. Hyperpolarized probes for MRI - Hyperpolarized contrast agents can be used to track metabolism and monitor characteristics of the tissue microenvironment by MRI.  NMR hyperpolarization techniques enable a wide range of functional MR imaging from the lungs to metabolic imaging of cancer, and are ideal for the imaging of minor changes in small molecules such as fumarate, choline, and glutamine.  The CSC routinely prepares isotopically labeled metabolites for the use in these studies.

      III. Lanthanide chelates for MRI - The unique paramagnetic properties of the lanthanide ions render them useful as magnetic resonance imaging (MRI) contrast agents and paramagnetic relaxation enhancement or pseudo-contact shift (PCS) tags in structural NMR applications. CSC has experience in the generation of lanthanide(III)-chelates and adducts.

      IV. 89Zr and 18F PET probes - Positron emission tomography (PET) provides information not only on biochemical, physiological and pharmacological processes but also offers the opportunity to study pharmacokinetics, metabolism, and mechanisms of action of novel and established drugs. We work with fluorine-18 and zirconium-89 PET isotopes to develop new probes or produce already existing probes. More than 40 different probes have been provided to the NIH investigators with an average of 150 production batches/year.

      V. Liposomes, protein purification, and antibody digestion - Large molecule expertise at IPDC includes conjugation of proteins and peptides, antibody digestion, and protein purification.  Antibodies and antibody fragments can be modified with chelating groups and fluorescent dyes.   Encapsulation of drugs in liposomes can improve delivery and solubility.  Liposome formulations can be prepared and extruded on a small scale.

      Publications

      R.A. Kulkarni, C.A. Briney, D.R. Crooks, S.E. Bergholtz, C. Mushti, S.J. Lockett, A.N. Lane T. W-M. Fan, R.E. Swenson, W.M. Linehan, J.L. Meier.
      ChemBioChem. 2019 Feb 01;20(3):360-365.