Wallenberg Foundation postdoctoral fellow
Honors & Awards
MIPS 2019 Young Investigator Award, Molecular Imaging Program at Stanford
Wallenberg Foundation postdoctoral fellowship, Knut and Alice Wallenberg Foundation (2017-2019)
International postdoctoral fellowship, Swedish Academy of Pharmaceutical Sciences (Sep 2016)
Benzelius Award for Outstanding Thesis, Royal Society of Sciences in Uppsala (2017)
Doctor of Philosophy, Uppsala Universitet (2016)
Master of Science, Uppsala Universitet (2009)
Current Research and Scholarly Interests
Development of radiolabelled tracers for imaging of maladaptive immune response in neurodegenerative disease
- The chemistry and pharmacology of putative synthetic cannabinoid receptor agonist (SCRA) new psychoactive substances (NPS) 5F-PY-PICA, 5F-PY-PINACA, and their analogs DRUG TESTING AND ANALYSIS 2019; 11 (7): 976–89
Imaging the invaders: TREM1 as a novel PET imaging biomarker of peripheral infiltrating myeloid cells and potential therapeutic target in multiple sclerosis.
SOC NUCLEAR MEDICINE INC. 2019
View details for Web of Science ID 000473116801543
Radiolabeling and pre-clinical evaluation of a first-in-class CD19 PET Tracer for imaging B cells in multiple sclerosis
SOC NUCLEAR MEDICINE INC. 2019
View details for Web of Science ID 000473116800129
Longitudinal TSPO-PET imaging of peripheral and central myeloid cells in a mouse model of complex regional pain syndrome.
Complex regional pain syndrome (CRPS) is a severely disabling disease characterized by pain, temperature changes, motor dysfunction and edema that most often occurs as an atypical response to a minor surgery or fracture. Inflammation involving activation and recruitment of innate immune cells, including both peripheral and central myeloid cells (i.e. macrophages and microglia, respectively), is a key feature of CRPS. However, the exact role and time-course of these cellular processes relative to the known acute and chronic phases of the disease are not fully understood. Positron emission tomography (PET) of translocator protein-18kDa (TSPO) is a method for non-invasively tracking these activated innate immune cells. Here, we reveal the temporal dynamics of peripheral and central inflammatory responses over 20 weeks in a tibial fracture/casting mouse model of CRPS through longitudinal TSPO-PET using [F]GE-180. PET tracer uptake quantification in the tibia revealed increased peripheral inflammation as early as 2 days post-fracture and lasting 7 weeks. Centralized inflammation was detected in the spinal cord and brain of fractured mice at 7 and 21 days post-injury. Spinal cord tissue immunofluorescent staining revealed TSPO expression in microglia (CD11b+) at 7 days, but was restricted mainly to endothelial cells (PECAM1+) at baseline and 7 weeks. Our data suggest early and persistent peripheral myeloid cell activation, and transient central microglial activation are limited to the acute phase of CRPS. Moreover, we show that TSPO-PET can be used to noninvasively monitor the spatiotemporal dynamics of myeloid cell activation in CRPS progression with potential to inform disease phase-specific therapeutics.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
View details for PubMedID 31095093
- Microwave-Assisted aza-Friedel-Crafts Arylation of N-Acyliminium Ions: Expedient Access to 4 -Aryl 3,4-Dihydroquinazolinones ACS OMEGA 2018; 3 (10): 14258–65
11C-DPA-713 versus 18F-GE-180: A preclinical comparison of TSPO-PET tracers to visualize acute and chronic neuroinflammation in a mouse model of ischemic stroke.
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
Neuroinflammation plays a key role in neuronal injury following ischemic stroke. Positron emission tomography (PET) imaging of translocator protein 18 kDa (TSPO) permits longitudinal, non-invasive visualization of neuroinflammation in both pre-clinical and clinical settings. Many TSPO tracers have been developed, however it is unclear which tracer is the most sensitive and accurate for monitoring the in vivo spatiotemporal dynamics of neuroinflammation across applications. Hence, there is a need for head-to-head comparisons of promising TSPO-PET tracers across different disease states. Accordingly, the aim of this study was to directly compare two promising second-generation TSPO tracers; 11C-DPA-713 and 18F-GE-180, for the first time at acute and chronic time-points following ischemic stroke. Methods: Following distal middle cerebral artery occlusion (dMCAO) or sham surgery, mice underwent consecutive PET/CT imaging with 11C-DPA-713 and 18F-GE-180 at 2, 6, and 28 days after stroke. T2-weighted magnetic resonance (MR) images were acquired to enable delineation of ipsilateral (infarct) and contralateral brain regions of interest (ROIs). PET images were analyzed by calculating % injected dose per gram (%ID/g) in MR-guided ROIs. Standardized uptake value ratios were determined using the contralateral thalamus as a pseudo-reference region (SUVTh). Ex vivo autoradiography and immunohistochemistry were performed to verify in vivo findings. Results: Significantly increased tracer uptake was observed in the ipsilateral compared to contralateral ROI (SUVTh, 50-60 min summed data) at acute and chronic time-points using 11C-DPA-713 and 18F-GE-180. Ex vivo autoradiography confirmed in vivo findings demonstrating increased TSPO-tracer uptake in infarcted versus contralateral brain tissue. Importantly, a significant correlation was identified between microglial/macrophage activation (CD68 immunostaining) and 11C-DPA-713-PET signal, that was not evident with 18F-GE-180. No significant correlations were observed between TSPO-PET and activated astrocytes (GFAP immunostaining). Conclusion: Both 11C-DPA-713 and 18F-GE-180-PET enable detection of neuroinflammation at early and chronic time-points following cerebral ischemia in mice. 11C-DPA-713-PET reflects the extent of microglial activation in infarcted dMCAO mouse brain tissue more accurately compared to 18F-GE-180, and appears to be slightly more sensitive. These results highlight the potential of 11C-DPA-713 for tracking microglial activation in vivo after stroke, and warrants further investigation in both pre-clinical and clinical settings.
View details for PubMedID 29976695
Microwave-Assisted aza-Friedel-Crafts Arylation of N-Acyliminium Ions: Expedient Access to 4-Aryl 3,4-Dihydroquinazolinones.
2018; 3 (10): 14258–65
A one-pot microwave-assisted aza-Friedel-Crafts arylation of N-acyliminium ions, generated in situ from o-formyl carbamates and different amines, is reported. This metal-free protocol provides rapid access to diverse 4-aryl 3,4-dihydroquinazolinones in excellent yield without any aqueous workup. A solvent-directed process for the selective aza-Friedel-Crafts arylation of electron-rich aryl/heteroaryl/butenyl-tethered N-acyliminium ions is also described.
View details for DOI 10.1021/acsomega.8b02298
View details for PubMedID 31458116
View details for PubMedCentralID PMC6644441
Acetic acid-promoted cascade N-acyliminium ion/aza-Prins cyclization: stereoselective synthesis of functionalized fused tricyclic piperidines
2017; 53 (13): 2110-2113
A novel acetic acid-promoted metal-free cascade N-acyliminium ion/aza-Prins cyclization of o-formyl carbamates and homoallylamines is reported. This one-pot protocol provides efficient and rapid access to masked cis-hydroxyhexahydropyrido[1,2-c]quinazolin-6-ones with concomitant generation of two stereogenic centers, four C-C/C-O/C-N bonds and two new rings in good yield and excellent diastereoselectivity.
View details for DOI 10.1039/c6cc09805c
View details for Web of Science ID 000395625700006
View details for PubMedID 28133651
- Synthesis of C-11-labeled Sulfonyl Carbamates through a Multicomponent Reaction Employing Sulfonyl Azides, Alcohols, and [C-11]CO CHEMISTRYOPEN 2016; 5 (6): 566-573
Microwave-Assisted Branching Cascades: A Route to Diverse 3,4-Dihydroquinazolinone-Embedded Polyheterocyclic Scaffolds
2016; 18 (20): 5392-5395
A novel metal-free microwave-assisted branching cascades strategy for the efficient synthesis of 3,4-dihydroquinazolinone-embedded polyheterocyclic scaffolds is reported. Starting from in situ generated key N-acyliminium ion precursors, 12 distinct and skeletally diverse polycyclic frameworks were accessed in a single step/pot via adjustment of the nucleophile(s) and reaction conditions. Postcascade functionalization of these compounds was also demonstrated, proving the utility of this method in accessing structurally diverse chemical entities.
View details for DOI 10.1021/acs.orglett.6b02774
View details for Web of Science ID 000386187300052
View details for PubMedID 27726402
Mild and Low-Pressure fac-Ir(ppy)(3)-Mediated Radical Aminocarbonylation of Unactivated Alkyl Iodides through Visible-Light Photoredox Catalysis
CHEMISTRY-A EUROPEAN JOURNAL
2016; 22 (27): 9155-9161
A novel, mild and facile preparation of alkyl amides from unactivated alkyl iodides employing a fac-Ir(ppy)3 -catalyzed radical aminocarbonylation protocol has been developed. Using a two-chambered system, alkyl iodides, fac-Ir(ppy)3 , amines, reductants, and CO gas (released ex situ from Mo(CO)6 ), were combined and subjected to an initial radical reductive dehalogenation generating alkyl radicals, and a subsequent aminocarbonylation with amines affording a wide range of alkyl amides in moderate to excellent yields.
View details for DOI 10.1002/chem.201601694
View details for Web of Science ID 000380271100021
View details for PubMedID 27271773
Sulfonyl Azides as Precursors in Ligand-Free Palladium-Catalyzed Synthesis of Sulfonyl Carbamates and Sulfonyl Ureas and Synthesis of Sulfonamides
JOURNAL OF ORGANIC CHEMISTRY
2016; 81 (7): 2681-2691
An efficient synthesis of sulfonyl carbamates and sulfonyl ureas from sulfonyl azides employing a palladium-catalyzed carbonylation protocol has been developed. Using a two-chamber system, sulfonyl azides, PdCl2, and CO gas, released ex situ from Mo(CO)6, were assembled to generate sulfonyl isocyanates in situ, and alcohols and aryl amines were exploited as nucleophiles to afford a broad range of sulfonyl carbamates and sulfonyl ureas. A protocol for the direct formation of substituted sulfonamides from sulfonyl azides and amines via nucleophilic substitution was also developed.
View details for DOI 10.1021/acs.joc.5b02755
View details for Web of Science ID 000373520200001
View details for PubMedID 26967791
- Multicomponent Reactions in 11C/12C Chemistry: – Targeting the Angiotensin II Subtype 2 Receptor Acta Universitatis Upsaliensis. 2016
- Rapid Access to Polyfunctionalized 3,4-Dihydroquinazolinones through a Sequential N-Acyliminium Ion Mannich Reaction Cascade EUROPEAN JOURNAL OF ORGANIC CHEMISTRY 2015: 7743-7755
- Cyclic amidines as precursors for imidazoles ARKIVOC 2015: 219-229
A microwave-assisted multicomponent synthesis of substituted 3,4-dihydroquinazolinones
ORGANIC & BIOMOLECULAR CHEMISTRY
2015; 13 (7): 2044-2054
A microwave-assisted, multicomponent protocol for the synthesis of substituted 3,4-dihydroquinazolinones via a novel cascade imine/cyclization/aza-Henry reaction sequence is reported. Starting from o-formyl carbamates, a series of structurally diverse 3,4-dihydroquinazolinones was synthesized via a cyclic iminium ion intermediate in moderate to excellent yields. Notably, the reaction is fast, flexible, simple to perform and tolerates a variety of functional groups.
View details for DOI 10.1039/c4ob02417f
View details for Web of Science ID 000349401300016
View details for PubMedID 25518892
Synthesis of Sulfonyl Azides via Diazotransfer using an Imidazole-1-sulfonyl Azide Salt: Scope and N-15 NMR Labeling Experiments
JOURNAL OF ORGANIC CHEMISTRY
2014; 79 (11): 4826-4831
Imidazole-1-sulfonyl azide hydrogen sulfate is presented as an efficient reagent for the synthesis of sulfonyl azides from primary sulfonamides. The described method is experimentally simple and high-yielding and does not require the addition of Cu salts. Furthermore, (15)N NMR mechanistic studies show the reaction proceeds via a diazo transfer mechanism. Imidazole-1-sulfonyl azide hydrogen sulfate provides a considerable advantage over existing diazo transfer reagents in terms of impact stability, cost, and ease of use.
View details for DOI 10.1021/jo500553q
View details for Web of Science ID 000337073900006
View details for PubMedID 24802878
- A microwave-assisted, propylphosphonic anhydride (T3P (R)) mediated one-pot Fischer indole synthesis TETRAHEDRON LETTERS 2011; 52 (34): 4417-4420
- Synthesis and evaluation of a C-11-labelled angiotensin II AT(2) receptor ligand JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS 2010; 53 (10): 616-624