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Patrick Riss

Professor

Email patrick.riss@kjemi.uio.no

Mobile phone +47 95 02 86 69 +4795028669

Room VU 65B

Username

Postal address Postboks 1033 0315 Oslo

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Research Interests

Radiopharmaceutical Chemistry
Production and Application of Medical Radionuclides
Radiochemical Method Development
Chemical Neuroscience

Teaching

KJM5950 - Radiopharmaceutical chemistry

Background

06/2009-03/2013, Wolfson Brain Imaging Centre, Cambridge, UK
05/2011-09/2011, National Institute of Mental Health, Bethesda, MD, USA
05/2008-07/2008, Brookhaven National Laboratory, Upton, NY, USA
06/2006-07/2006, Institute of Organic Chemistry and Catalysis, TU Delft, The Netherlands
10/2004-06/2009,Institute of Nuclear Chemistry, Mainz, Germany

Awards

12/2012, Oral Presentation Prize of the UK PET Chemistry Group
09/2009, Dissertation Prize of the Gesellschaft deutscher Chemiker (GdCh)
07/2009, Dissertation Prize of the ‘Freunde der Universität Mainz. e.V.’
07/2007, Attendant: 57th Lindau Nobel Laureates Meeting

Collaboration (alphabetical)

National

Ira Ronit Haraldsen, OUS-Rikshospitalet, http://www.ous-research.no/home/iraharaldsen/Group%20members/8376

Jon Petter Omtvedt, SAFE http://www.mn.uio.no/kjemi/personer/vit/jonpo/index.html

Rune Sundset,UNN/UiT

Thor Audun Saga, Norsk Medisinsk Syklotronsenter AS, http://www.petsenteret.no

International

Dr Franklin I Aigbirhio, University of Cambridge, UK http://www.neuroscience.cam.ac.uk/directory/profile.php?fia20

Dr Tim D Fryer, University of Cambridge, UK http://www.neuroscience.cam.ac.uk/directory/profile.php?tdf21

Prof Olaf Prante, Erlangen University Hospital, Germany http://www.efs.uni-erlangen.de/prof/prante.shtml

Prof Frank Roesch, University of Mainz, Germany http://www.kernchemie.uni-mainz.de

Prof Peter Scott, Radiology, Ann Arbor

Riss PJ, Hong YT, Marton J, Caprioli D, Williamson DJ, Ferrari V, Saigal N, Roth B, Henriksen G, Aigbirhio FI, Fryer TD, Dalley JW (2013) J Nucl Med. 54(2):299-305

Riss PJ, Lu S, Telu S, Aigbirhio FI, Pike VW (2012) Angew. Chem. Int. Ed. 51 (11): 2698–2702 Highlighted in SYNFACTS 2012

Riss PJ, Aigbirhio FI (2011) Chem Commun 47(43):11873-11875

Riss PJ, Hong YT, Williamson D, Caprioli D, Sitnikov S, Ferrari V, Sawiak SJ, Baron JC, Dalley JW, Fryer TD, Aigbirhio FI (2011) J Cereb Blood Flow Metab 31(12): 2334-2342

Roesch F, Riss PJ (2010) Curr Top Med Chem 10(16):1633-68

Ghazaiean, Mobin; Riss, Patrick Johannes; Mardanshahi, Alireza & Molavipordanjani, Sajjad (2025). Fibrotic Disease: from Signaling Pathways and Biomarkers to Molecular Imaging. Molecular Imaging and Biology. ISSN 1536-1632. doi: 10.1007/s11307-025-02038-9. Full text in Research Archive
Maqbool, Mudasir; Jakobsson, Jimmy Erik; Alluri, Santosh Reddy; Kramer, Vasko & Riss, Patrick Johannes (2024). A protocol for controlled reactivity shift in the 2,2-difluorovinyl motif used for selective S–18F and C–18F bond formation. Communications chemistry. 7(1). doi: 10.1038/s42004-024-01132-3. Full text in Research Archive Show summary
Positron emission tomography (PET) is a powerful imaging technique for biomedical research, drug development and medical diagnosis. The power of PET lies in biochemically selective radiotracers, labelled with positron emitters like fluorine-18 image chemical processes in vivo. A rapid and remarkably efficient, unprecedented protocol to select between S-F and C-F bond formation based on activation of 1,1-difluoroethylene groups followed by selective oxidation or reduction is described. While transition metal mediated conditions can be employed, the reaction proceeds in high yield using unobjectionable chemical reagents amenable to routine radiotracer production. The latter bodes well for facile clinical translation of the method. The new technique affords radiotracers and the labelling reagent 2,2-difluoro-2-(fluoro-18F)ethyl 4-methylbenzenesulfonate ([18F]1b) in excellent yield. Following oxygenation of the reaction mixture with medical oxygen or air, sulfonyl fluorides are obtained as the primary product. The new protocol was employed in a proof of principle to develop a radiometric assay for quantitation of sulfonylation yield with sulfonyl fluoride reagents. With operational ease and mild conditions, the method bodes a high potential for radiolabelling of biomolecules, known enzyme inhibitors and other temperature-sensitive compounds.
Bow, John-Paul James; Adami, Valentina; Marasco, Agostino; Grønnevik, Gaute; Rivers, Dean A. & Alvaro, Guiseppe [Show all 7 contributors for this article] (2022). A direct fixation of CO<inf>2</inf> for isotopic labelling of hydantoins using iodine-phosphine charge transfer complexes. Chemical Communications. ISSN 1359-7345. 58(54), p. 7546–7549. doi: 10.1039/d2cc01754g. Full text in Research Archive Show summary
Herein, we report a method for the isotopic labelling of hydantoins directly from CO2 by means of trimethyl-λ5-phosphine diiodide mediated carbonyl insertion. The method is suitable for 13C-labelling of diverse substrates and was implementated for 11C-labelling in PET-imaging facilities for the synthesis of radiotracers. Isolated yields of 90% and radiochemical yields of 89% were achieved for hydantoin containing drug candidates in formulation within 30 min with high molar activity (>400 MBq nmol−1).
Garcia, Raul Manuel Perez & Riss, Patrick Johannes (2022). Mild, Organo-Catalysed Borono-Deamination as a Key to Late-Stage Pharmaceutical Precursors and 18F-Labelled Radiotracers. Frontiers in Chemistry. 10. doi: 10.3389/fchem.2022.884478. Full text in Research Archive Show summary
A tris(pentafluorophenyl)borane catalysed method for the synthesis of boronic acid esters from aromatic amines in yields of up to 93% was devised. Mild conditions, benign reagents, short reaction times, low temperatures and a wide substrate scope characterize the method. The reaction was found applicable to the synthesis of boronic acid ester derivatives of complex drug molecules in up to 86% isolated yield and high purity suitable for labelling. These boronates were subsequently labelled with [ 18 F]fluoride ion in radiochemical yields of up to 55% with and even without isolation of the boronate-intermediate.
Lehnert, Wencke; Riss, Patrick Johannes; Mendoza, Ana Hurtado de; Lopez, Sandra; Fernandez, Gonzalo & Ilheu, Marcelo [Show all 8 contributors for this article] (2022). Whole-body biodistribution and radiation dosimetry of [18F]PR04.MZ: a new PET radiotracer for clinical management of patients with movement disorders. EJNMMI Research. 12(1). doi: 10.1186/s13550-021-00873-9. Full text in Research Archive Show summary
Purpose [18F]PR04.MZ is a new PET imaging agent for dopamine transporters, providing excellent image quality and allowing for the evaluation of patients with movement disorders such as Parkinson’s disease. The objective of this study was to evaluate the biodistribution and radiation dosimetry of [18F]PR04.MZ by serial PET imaging. Methods Six healthy subjects (n = 3 males, n = 3 females) were enrolled in this study. A series of 14 whole-body PET/CT scans were acquired until 5.5 h post-injection of 200 ± 11 MBq of [18F]PR04.MZ. After rigid co-registration, volumes of interest were outlined either on CT or PET images. Time-integrated activity coefficients were calculated for selected source organs. Organ absorbed doses, and the effective dose were calculated using IDAC-Dose 2.1. Results Physiological uptake of [18F]PR04.MZ was mainly observed in the striatum, brain, liver, gall bladder, intestine, red marrow and cortical bone. [18F]PR04.MZ was primarily excreted via hepatobiliary clearance and, to a lower extent, via renal clearance. The normalized absorbed doses were highest in gall bladder wall (32.2 ± 6.4 µGy/MBq), urinary bladder wall (27.2 ± 4.5 µGy/MBq), red marrow (26.5 ± 1.4 µGy/MBq), cortical bone surface (26.3 ± 2.5 µGy/MBq), liver (22.5 ± 1.8 µGy/MBq) and kidneys (21.8 ± 1.1 µGy/MBq). The effective dose according to ICRP 60 and 103 was 16.3 ± 1.1 and 16.6 ± 1.5 µSv/MBq, respectively. Conclusion [18F]PR04.MZ has a favourable dosimetry profile, comparable to those of other 18F-labelled PET tracers, and is suitable for larger clinical applications. Trial registration CEC SSM Oriente, Santiago, Chile, permit 20140520.
Juri, Carlos; Kramer, Vasko; Riss, Patrick; Soza-Ried, Cristian; Haeger, Arlette & Pruzzo, Rossana [Show all 9 contributors for this article] (2021). 18F]PR04.MZ PET/CT Imaging for Evaluation of Nigrostriatal Neuron Integrity in Patients With Parkinson Disease. Clinical Nuclear Medicine. ISSN 0363-9762. 46(2), p. 119–124. doi: 10.1097/RLU.0000000000003430. Full text in Research Archive Show summary
Introduction Degeneration of dopaminergic, nigrostriatal neurons is the hallmark of Parkinson disease (PD), and PET quantification of dopamine transporters is a widely accepted method for differential diagnosis between idiopathic PD and essential tremor. [18F]PR04.MZ is a new PET tracer with excellent imaging properties allowing for precise quantification of striatal and extrastriatal dopamine transporter. Here we describe our initial experience with [18F]PR04.MZ PET/CT in a larger cohort of healthy controls and PD patients as a proof-of-concept study for this tracer. Methods Eighteen healthy subjects, 19 early PD patients (Hoehn-Yahr I–II), and 13 moderate-advanced PD patients (Hoehn-Yahr III–IV) underwent static PET/CT scans 60 to 90 minutes after injection of 5.16 ± 1.03 mCi (191 ± 38 MBq) [18F]PR04.MZ. Specific binding ratios (SBRs) were calculated for caudate nucleus, anterior putamen, posterior putamen, substantia nigra (SNpc), compared between different groups and correlated with clinical ratings. Results [18F]PR04.MZ showed very high and specific uptake in the putamen, caudate, and substantia nigra pars compacta and very low nonspecific binding in other brain regions, and SBR values for the control group were 22.3 ± 4.1, 19.1 ± 3.5, and 5.4 ± 1.2, respectively. A reduction of SBR values was observed in all regions and in both initial and moderate PD, ranging from 35% to 89% (P < 0.001). The observed pattern of reduction was posterior putamen > anterior putamen > substantia nigra pars compacta > caudate, with contralateral posterior putamen being the most affected region. Rostrocaudal depletion gradient was evident in all PD patients and progression correlated with motor manifestations. Conclusions [18F]PR04.MZ PET/CT is a highly sensitive imaging modality for the detection of dopaminergic deficit in nigrostriatal pathways in PD.
Garcia, Raul Manuel Perez; Grønnevik, Gaute & Riss, Patrick (2021). A General Protocol for Cu-Mediated Fluoro-deamination: Sandmeyer Fluorination of Diverse Aromatic Substrates. Organic Letters. ISSN 1523-7060. 23(3), p. 1011–1015. doi: 10.1021/acs.orglett.0c04209. Full text in Research Archive Show summary
A Cu(I)-mediated fluoro-deamination method for nucleophilic radiofluorination was devised. The method affords fluorinated aromatic products directly from anilines under both no-carrier added and stoichiometric conditions. Isolated radiochemical yields range from 11% to 81% with high radiochemical purities and a molar activity of 58 MBq/nmol. The reaction conditions were implemented successfully in an automated process for production of (S)-4[18F]fluorogluthetimide on a radiosynthesis module.
Bow, John-Paul J. & Riss, Patrick Johannes (2021). Phosgene-Free Carbonyl Insertion: Hot Advances in 11C-Chemistry. Chemistry-Methods. 1(3), p. 139–141. doi: 10.1002/cmtd.202000029. Full text in Research Archive
Stefan, Katja; Leck, Lionel Yi Wen; Namasivayam, Vigneshwaran; Bascuñana, Pablo; Huang, Michael Li-Hsuan & Riss, Patrick [Show all 9 contributors for this article] (2020). Vesicular ATP-binding cassette transporters in human disease: relevant aspects of their organization for future drug development. Future Drug Discovery. 4:FDD51(2), p. 1–8. doi: 10.4155/fdd-2020-0025. Full text in Research Archive
Ott, Julian; Spilhaug, Mona M.; Maschauer, Simone; Rafique, Waqas; Jakobsson, Jimmy Erik & Hartvig, Karoline [Show all 10 contributors for this article] (2020). Pharmacological Characterization of Low-to-Moderate Affinity Opioid Receptor Agonists and Brain Imaging with 18F-Labeled Derivatives in Rats. Journal of Medicinal Chemistry. ISSN 0022-2623. 63(17), p. 9484–9499. doi: 10.1021/acs.jmedchem.0c00683. Full text in Research Archive Show summary
The 3,4-dichloro-N-(1-(dimethylamino)cyclohexyl)methyl benzamide scaffold was studied as a template for 18F-positron emission tomography (18F-PET) radiotracer development emphasizing sensitivity to changes in opioid receptor (OR) occupancy over high affinity. Agonist potency, binding affinity, and relevant pharmacological parameters of 15 candidates were investigated. Two promising compounds 3b and 3e with μ-OR (MOR) selective agonist activity in the moderate range (EC50 = 1–100 nM) were subjected to 18F-fluorination, autoradiography, and small-animal PET imaging. Radioligands [18F]3b and [18F]3e were obtained in activity yields of 21 ± 5 and 23 ± 4% and molar activities of 25–40 and 200–300 GBq/μmol, respectively. Displaceable binding matching MOR distribution in the brain was confirmed by imaging. Radioligands showed a rapid pharmacokinetic profile; however, metabolite-corrected, blood-based modeling was required for data analysis. Observed BPND was low, although treatment with naloxone leads to a marked decrease in specific binding, confirming the discovery of a new template for 18F-labeled OR-agonist PET ligands.
Gurin, Andrey; Chakrova, Yelena; Matveyeva, Ilona & Riss, Patrick Johannes (2020). Optimization of reaction parameters for the synthesis of 177Lu-DOTAELA. Revista de chimie (Bucuresti). ISSN 0034-7752. 71(8), p. 55–62. doi: 10.37358/RC.20.8.8278. Full text in Research Archive
Gurin, A.N.; Riss, Patrick; Chakrova, E.T.; Matveyeva, I.V. & Kadyrbaev, E.A. (2020). Study of the Purification of 177Lu-DOTAELA Complex. Pharmaceutical Chemistry Journal. ISSN 0091-150X. 54(1), p. 64–68. doi: 10.1007/s11094-020-02157-3. Full text in Research Archive
Wærsted, Frøydis Meen; Riss, Patrick & Skipperud, Lindis (2020). The effect of water exchange on the leaching of alum shale. Applied Geochemistry. ISSN 0883-2927. 119. doi: 10.1016/j.apgeochem.2020.104610. Full text in Research Archive Show summary
In recent years, there has been an increasing focus on the adverse environmental effects from naturally occurring radioactive materials (NORM). Acid rock drainage (ARD) produced by debris from mining and construction work is a major environmental issue, leading to release of highly acidic water as well as both NORM and stable trace elements. Batch leaching experiments with alum shale demonstrated that exchange of water will increase leaching of elements whose mobility is limited by concentration effects, such as Ba and the extremely radiotoxic, naturally occurring uranium daughter 226Ra. Periods of drying the alum shale in air increased leaching of Li, V, Mo and 226Ra, increasing their mobility in the environment. Acid production from sulphide oxidation did not cause pH values below 6.4 in the 28 weeks experiment. However, exchange of water did lead to reduction of inherent buffer capacity of the alum shale, which increases the risk of ARD as well as likely reducing the time before onset of ARD.
Kramer, Vasko; Brooks, Allen; Haeger, Arlette; Kuljs, Rodrigo; Rafique, Waqas Muhammad & Koeppe, Robert [Show all 11 contributors for this article] (2020). Evaluation of [18F]N-methyl-lansoprazole as a tau PET imaging agent in first-in-human studies. ACS Chemical Neuroscience. 11(3), p. 427–435. doi: 10.1021/acschemneuro.9b00639. Full text in Research Archive
Bekker, Roberto Bartholomeus Wilhelmus; Fjellaksel, Richard; Hjornevik, Trine; Nuruddin, Syed; Rafique, Waqas & Hansen, Jørn H [Show all 9 contributors for this article] (2020). Discovery of a lead brain-penetrating gonadotropin-releasing hormone receptor antagonist with saturable binding in brain. ChemMedChem. ISSN 1860-7179. 15(17), p. 1624–1628. doi: 10.1002/cmdc.202000256. Full text in Research Archive Show summary
We report the synthesis, radiosynthesis and biological characterisation of two gonadotropin‐releasing hormone receptor (GnRH−R) antagonists with nanomolar binding affinity. A small library of GnRH−R antagonists was synthesised in 20–67 % overall yield with the aim of identifying a high‐affinity antagonist capable of crossing the blood–brain barrier. Binding affinity to rat GnRH−R was determined by autoradiography in competitive‐binding studies against [125l]buserelin, and inhibition constants were calculated by using the Cheng–Prusoff equation. The radioligands were obtained in 46–79 % radiochemical yield and >95 % purity and with a molar activity of 19–38 MBq/nmol by direct nucleophilic radiofluorination. Positron emission tomography imaging in rat under baseline conditions in comparison to pretreatment with a receptor‐saturating dose of GnRH antagonist revealed saturable uptake (0.1 %ID/mL) into the brain.
Pitman, Kathinka; Alluri, Santosh Reddy; Kristian, Alexandr; Aarnes, Eva-Katrine; Lyng, Heidi & Riss, Patrick [Show all 7 contributors for this article] (2019). Influx rate of 18F-fluoroaminosuberic acid reflects cystine/glutamate antiporter expression in tumour xenografts. European Journal of Nuclear Medicine and Molecular Imaging. ISSN 1619-7070. 46(10), p. 2190–2198. doi: 10.1007/s00259-019-04375-8. Full text in Research Archive
Fjellaksel, Richard; Moldes-Anaya, Angel; Vasskog, Terje; Oteiza, Ana; Martin-Armas, Maria Montserrat & Hjelstuen, Ole Kristian [Show all 9 contributors for this article] (2019). Evaluation by metabolic profiling and in vitro autoradiography of two promising GnRH‐receptor ligands for brain SPECT imaging. Journal of labelled compounds & radiopharmaceuticals. ISSN 0362-4803. p. 1–13. doi: 10.1002/jlcr.3820. Full text in Research Archive Show summary
The increased expression of gonadotropin releasing hormone receptor (GnRH‐R) in brain has been strongly linked to Alzheimer disease. Therefore, the development of radiolabeled imaging agents for GnRH‐R is relevant for early diagnosis of Alzheimer disease. We have recently disclosed the discovery of two promising compounds displaying nanomolar‐range affinity for the GnRH‐R. In the present study, a preclinical evaluation of the compound properties was performed to evaluate their potential as single photon emission computed tomography (SPECT) radiotracers for imaging the GnRH‐receptor. The compounds were assessed in vitro by performing serum stability analysis by human and rat serum, metabolic profiling by human liver microsomes, and exploratory rat brain autoradiography. The investigated compounds displayed satisfactory stability against human, rat serum, and liver microsomal metabolism, which favors their potential as SPECT‐imaging agents. Additionally, we identified and quantified the formation rate of the metabolites by fragmentation of up to five mass spectrometric stages. The GnRH‐R rat brain specificity of these compounds was tested in competition with a known ligand for the receptor and the in vitro autoradiography confirmed that compounds 3 and 4 binds to rat GnRH‐R in different rat brain regions.
Jakobsson, Jimmy Erik; Gourni, Eleni; Shivashankar, Shivashankar; Brito, Beatriz & Riss, Patrick (2019). Synthesis and Characterization in Rodent Brain of the Subtype-Selective NR2B NMDA Receptor Ligand [11C]Ro04-5595 as a Potential Radiotracer for Positron Emission Tomography. ACS Omega. 4(6), p. 9925–9931. doi: 10.1021/acsomega.9b00357. Full text in Research Archive
Alluri, Santosh Reddy; Pitman, Kathinka; Malinen, Eirik & Riss, Patrick (2019). Synthesis, radiosynthesis, and positron emission tomography neuroimaging using 5-[18 F]fluoro-L-amino suberate. Journal of labelled compounds & radiopharmaceuticals. ISSN 0362-4803. 63(1), p. 6–14. doi: 10.1002/jlcr.3814. Full text in Research Archive Show summary
System xc‐ (Sxc‐) has emerged as a new biological target for PET studies to detect oxidative and excitotoxic stress. Notably, applications have, thus far, been limited to tumour imaging although Sxc‐) may play a major role in neurodegeneration. The synthesis procedures of tosylate precursor and its translation to Sxc‐ PET tracer 5[18F]fluoro‐L‐amino suberate by manual and automated radiosyntheses are described. A brain‐PET study has been conducted to evaluate the tracer uptake into brain in healthy mice.
Kramer, Vasko; Juri, Carlos; Riss, Patrick; Pruzzo, Rossana; Soza-Ried, Cristian & Flores, Jonathan [Show all 10 contributors for this article] (2019). Pharmacokinetic evaluation of [18F]PR04.MZ for PET/CT imaging and quantification of dopamine transporters in the human brain. European Journal of Nuclear Medicine and Molecular Imaging. ISSN 1619-7070. p. 1–11. doi: 10.1007/s00259-019-04594-z. Full text in Research Archive
Fjellaksel, Richard; Sundset, Rune; Riss, Patrick & Hansen, Jørn H (2018). Copper-mediated late-stage iodination and 123I-labelling of triazole-benzimidazole bioactives. Synlett : Accounts and Rapid Communications in Synthetic Organic Chemistry. ISSN 0936-5214. 29(11), p. 1491–1495. doi: 10.1055/s-0036-1591985. Full text in Research Archive
Fjellaksel, Richard; Dugalic, Damir; Demissie, Taye Beyene; Riss, Patrick; Hjelstuen, Ole Kristian & Sundset, Rune [Show all 7 contributors for this article] (2018). An acylation-Finkelstein approach to radioiodination of bioactives: The role of amide group anchimeric assistance. Journal of Physical Organic Chemistry. ISSN 0894-3230. 31(7), p. 1–12. doi: 10.1002/poc.3835. Full text in Research Archive Show summary
Herein, we report a straightforward sequential acylation‐Finkelstein approach to achieve iodination of amine containing bioactives. The utility was demonstrated by successful radiolabelling with 123I in high radiochemical yield. Moreover, microwave‐assisted Finkelstein reaction can be employed to enhance conversion and reaction rates to obtain the desired iodides. The method is of interest for radioiodination of amine‐containing bioactives. The mechanistic details of the iodination process were studied by kinetics and density functional theory calculations, which revealed the mechanistic complexity of the reaction involving amide group anchimeric assistance. We disclose a number of fundamental aspects of amide group anchimeric assistance in substitution reactions.
Jakobsson, Jimmy Erik; Grønnevik, Gaute; Rafique, Waqas; Hartvig, Karoline & Riss, Patrick (2018). Formamide as an Unconventional Amine Protecting Group for PET Radiochemistry. European Journal of Organic Chemistry. ISSN 1434-193X. 2018(27), p. 3701–3704. doi: 10.1002/ejoc.201800554. Full text in Research Archive
Munthe, Else; Riss, Patrick; Saga, T.; Haraldsen, Ira Hebold; Grad, Iwona & Bogsrud, Trond [Show all 7 contributors for this article] (2018). FDG-based quantitative comparison of glucose metabolism in vitro, exemplified by a head-to-head comparison between a triple-negative breast cancer cell line and a non-malignant foetal cell line. Clinical Physiology and Functional Imaging. ISSN 1475-0961. 38(1), p. 34–37. doi: 10.1111/cpf.12378. Full text in Research Archive
Fjellaksel, Richard; Oteiza, Ana; Martin-Armas, Montserrat; Riss, Patrick; Hjelstuen, Ole Kristian & Kuttner, Samuel [Show all 8 contributors for this article] (2018). First in vivo evaluation of a potential SPECT brain radiotracer for the gonadotropin releasing hormone receptor. BMC Research Notes. 11(1), p. 1–6. doi: 10.1186/s13104-018-3924-2. Full text in Research Archive Show summary
Objectives: In vivo evaluations of a gonadotropin releasing hormone-receptor single photon emission computed tomography radiotracer for non-invasive detection of gonadotropin releasing homone-receptors in brain. Results: We have used a simple, robust and high-yielding procedure to radiolabel an alpha-halogenated bioactive compound with high radiochemical yield. Literature findings showed similar alpha-halogenated compounds suitable for in vivo evaluations. The compound was found to possess nano molar affinity for the gonadotropin releasing hormone-receptor in a competition dependent inhibition study. Furthermore, liquid chromatography-mass spectrometry analysis in saline, human and rat serum resulted in 46%, 52% and 44% stability after incubation for 1 h respectively. In addition, rat brain single photon emission computed tomography and biodistribution studies gave further insight into the nature of the compound as a radiotracer.
Jakobsson, Jimmy Erik & Riss, Patrick (2018). Transition metal free, late-stage, regiospecific, aromatic fluorination on a preparative scale using a KF/crypt-222 complex. RSC Advances. 8(38), p. 21288–21291. doi: 10.1039/c8ra03757d. Full text in Research Archive
Alluri, Santosh Reddy & Riss, Patrick (2018). Poly(ADP-ribose) polymerase in neurodegeneration: Radiosynthesis and radioligand binding in ARC-SWE tg mice. ACS Chemical Neuroscience. 9(6), p. 1259–1263. doi: 10.1021/acschemneuro.8b00053. Full text in Research Archive
Alluri, Santosh Reddy & Riss, Patrick (2018). Stereospecific radiosynthesis of 3-fluoro amino acids: access to enantiomerically pure radioligands for positron emission tomography. Organic and biomolecular chemistry. ISSN 1477-0520. 16(13), p. 2219–2224. doi: 10.1039/c8ob00184g. Full text in Research Archive
Rafique, Waqas; Kramer, Vasko; Pardo, Tania; Smits, René; Spilhaug, Mona M. & Hoepping, Alexander [Show all 11 contributors for this article] (2018). Image-guided development of heterocyclic sulfoxides as ligands for tau neurofibrillary tangles: From first-in-man to second-generation ligands. ACS Omega. 3(7), p. 7567–7579. doi: 10.1021/acsomega.8b00975. Full text in Research Archive
Jakobsson, Jimmy Erik; Grønnevik, Gaute & Riss, Patrick (2017). Organocatalyst-assisted Ar-18F bond formation: A universal procedure for direct aromatic radiofluorination. Chemical Communications. ISSN 1359-7345. 53(96), p. 12906–12909. doi: 10.1039/c7cc07211b. Full text in Research Archive
Tukun, Feng-Ling; Olberg, Dag Erlend; Riss, Patrick; Haraldsen, Ira Hebold; Kåss, Anita Anjali Suri & Klaveness, Jo (2017). Recent development of non-peptide GnRH antagonists. Molecules. ISSN 1431-5157. 22:2188(12), p. 1–25. doi: 10.3390/molecules22122188. Full text in Research Archive Show summary
The decapeptide gonadotropin-releasing hormone, also referred to as luteinizing hormone-releasing hormone with the sequence (pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2) plays an important role in regulating the reproductive system. It stimulates differential release of the gonadotropins FSH and LH from pituitary tissue. To date, treatment of hormone-dependent diseases targeting the GnRH receptor, including peptide GnRH agonist and antagonists are now available on the market. The inherited issues associate with peptide agonists and antagonists have however, led to significant interest in developing orally active, small molecule, non-peptide antagonists. In this review, we will summarize all developed small molecule GnRH antagonists along with the most recent clinical data and therapeutic applications.
Rafique, Waqas; Shivashankar, Shivashankar; Milde, Mona & Riss, Patrick (2017). Reaching out for sensitive evaluation of the Mu opioid receptor in vivo: positron emission tomography imaging of the Agonist [11C]AH7921. ACS Chemical Neuroscience. 8(9), p. 1847–1852. doi: 10.1021/acschemneuro.7b00075. Full text in Research Archive
Fjellaksel, Richard; Boomgaren, Marc; Sundset, Rune; Haraldsen, Ira Hebold; Hansen, Jørn H & Riss, Patrick (2017). Small molecule piperazinyl-benzimidazole antagonists of the gonadotropin-releasing hormone (GnRH) receptor. MedChemComm. ISSN 2040-2503. 8(10), p. 1965–1969. doi: 10.1039/c7md00320j. Full text in Research Archive Show summary
In this communication, we report the synthesis and characterization of a library of small molecule antagonists of the human gonadotropin releasing hormone receptor based upon the 2-(4-tert-butylphenyl)-4-piperazinyl-benzimidazole scaffold via Cu-catalysed azide alkyne cycloaddition. Our main purpose was to find a more soluble compound based on the WAY207024 lead with nanomolar potency to inhibit the GnRH receptor. A late stage diversification by the use of click chemistry was, furthermore developed to allow for expansion of the library in future optimisations. All compounds were tested in a functional assay to determine the individual potency of inhibiting stimulation of the receptor by the endogenous agonist GnRH. In conclusion, we found that compound 8a showed improved solubility compared to WAY207024 and nanomolar affinity to GnRH receptor.
Sommer, Theis; Bjerregaard-Andersen, Kaare; Simensen, Stine Marie; Jensen, Jan K.; Jochimsen, Bjarne & Riss, Patrick [Show all 8 contributors for this article] (2015). Enzymatic detection and quantification assay of isatin, a putative stress biomarker in blood. ACS Chemical Neuroscience. 6(8), p. 1353–1360. doi: 10.1021/cn500346x. Full text in Research Archive
Maschauer, Simone; Haller, Adelina; Riss, Patrick; Kuwert, Torsten; Prante, Olaf & Cumming, Paul (2015). Specific binding of [18F]fluoroethyl-harmol to monoamine oxidase A in rat brain cryostat sections, and compartmental analysis of binding in living brain. Journal of Neurochemistry. ISSN 0022-3042. 135(5), p. 908–917. doi: 10.1111/jnc.13370. Full text in Research Archive
Cumming, Paul; Maschauer, Simone; Riss, Patrick; Grill, Eva; Pischetsrieder, Monika & Kuwert, Torsten [Show all 7 contributors for this article] (2015). Perturbed Development of Striatal Dopamine Transporters in Fatty Versus Lean Zucker Rats: a Follow-up Small Animal PET Study. Molecular Imaging and Biology. ISSN 1536-1632. 17(4), p. 521–528. doi: 10.1007/s11307-014-0811-7. Full text in Research Archive
Rühl, Thomas; Rafique, Waqas; Lien, Vegard Torp & Riss, Patrick (2014). Cu(I)-mediated 18F-trifluoromethylation of arenes: Rapid synthesis of 18F-labeled trifluoromethyl arenes†. Chemical Communications. ISSN 1359-7345. 50(45), p. 6056–6059. doi: 10.1039/c4cc01641f. Full text in Research Archive
Cumming, Paul; Maschauer, Simone; Riss, Patrick; Tschammer, Nuska; Fehler, Stefanie K. & Heinrich, Markus R. [Show all 8 contributors for this article] (2014). Radiosynthesis and validation of 18 F-FP-CMT, a phenyltropane with superior properties for imaging the dopamine transporter in living brain. Journal of Cerebral Blood Flow and Metabolism. ISSN 0271-678X. 34(7), p. 1148–1156. doi: 10.1038/jcbfm.2014.63. Full text in Research Archive
Kristian, Alexandr; Riss, Patrick; Qu, Hong; Milde, Mona; Schoultz, Bent Wilhelm & Engebråten, Olav [Show all 8 contributors for this article] (2014). Positron emission tomography and pharmacokinetics of 2-[18F]-fluoroethyl choline for metabolic studies in breast cancer xenografts. Acta Oncologica. ISSN 0284-186X. 53(8), p. 1086–1092. doi: 10.3109/0284186X.2014.934398. Full text in Research Archive
Lien, Vegard Torp & Riss, Patrick (2014). Radiosynthesis of [18F]trifluoroalkyl groups: Scope and limitations. BioMed Research International. ISSN 2314-6133. 2014:380124. doi: 10.1155/2014/380124. Full text in Research Archive
Riss, Patrick; Brichard, Laurent; Ferrari, Valentina; Williamson, David J.; Fryer, Tim D. & Hong, Young T. [Show all 8 contributors for this article] (2013). Radiosynthesis and characterization of astemizole derivatives as lead compounds toward PET imaging of tau-pathology. MedChemComm. ISSN 2040-2503. 4(5), p. 852–855. doi: 10.1039/c3md00017f. Full text in Research Archive
Riss, Patrick; Hoehnemann, Sabine; Piel, Markus & Roesch, F. (2013). Two-step radiosynthesis of [18F]FE--CIT and [18F]PR04.MZ. Journal of labelled compounds & radiopharmaceuticals. ISSN 0362-4803. 56(7), p. 356–359. doi: 10.1002/jlcr.3032. Full text in Research Archive
Riss, Patrick; Hong, Young T.; Marton, Janos; Caprioli, Daniele; Williamson, Derek & Ferrari, Valentina [Show all 12 contributors for this article] (2013). Synthesis and Evaluation of F-18-FE-PEO in Rodents: An F-18-Labeled Full Agonist for Opioid Receptor Imaging. Journal of Nuclear Medicine. ISSN 0161-5505. 54(2), p. 299–305. doi: 10.2967/jnumed.112.108688. Full text in Research Archive

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Gurin, A.N.; Riss, Patrick Johannes; Chakrova, E.T.; Matveyeva, I.V. & Kadyrbaev, E.A. (2020). Correction to: Study of the Purification of 177Lu-DOTAELA Complex (Pharmaceutical Chemistry Journal, (2020), 54, 1, (64-68), 10.1007/s11094-020-02157-3). Pharmaceutical Chemistry Journal. ISSN 0091-150X. 54(7), p. 776–776. doi: 10.1007/s11094-020-02270-3. Full text in Research Archive
Gee, Antony D.; Andersson, Jan; Bhalla, Rajiv; Choe, Yearn Seong; Dick, David W. & Herth, Matthias M. [Show all 28 contributors for this article] (2020). Training the next generation of radiopharmaceutical scientists. Nuclear Medicine and Biology. ISSN 0969-8051. 88-89, p. 10–13. doi: 10.1016/j.nucmedbio.2020.06.004. Full text in Research Archive
Fjellaksel, Richard; Oteiza, Ana; Martin, armas maria montserrat; Hansen, Jørn H; Moldes-Anaya, Angel & Vasskog, Terje [Show all 9 contributors for this article] (2018). Development and evaluation of gonadotropin releasing hormone SPECT radioligands. Full text in Research Archive
Fjellaksel, Richard; Hansen, Jørn H; Moldes-Anaya, Angel; Martin, armas maria montserrat; Oteiza, Ana & Riss, Patrick [Show all 7 contributors for this article] (2017). Development and evaluation of gonadotropin releasing hormone (GnRH) SPECT radioligands. Full text in Research Archive
Prante, Olaf; Haubner, Roland; Riss, Patrick & Neumaier, Bernd (2014). Recent trends in pharmaceutical radiochemistry for molecular PET imaging. BioMed Research International. ISSN 2314-6133. 2014. doi: 10.1155/2014/890540. Full text in Research Archive
Kristian, Alexandr; Riss, Patrick; Qu, Hong; Milde, Mona; Schoultz, Bent Wilhelm & Engebråten, Olav [Show all 8 contributors for this article] (2014). Pharmacokinetic modeling of dynamic 18F‐Choline PET reflects choline metabolism in breast carcinoma xenografts. Full text in Research Archive
Hartvig, Karoline; Riss, Patrick; Hjelstuen, Olaug & Brevik, Ellen Mengshoel (2020). Synthesis and evaluation of radiopharmaceuticals for targeted radionuclide therapy. Universitetet i Oslo. Full text in Research Archive Show summary
Nowadays, radionuclides play an important role in oncology, especially in the developing field of targeted radionuclide therapy (TRT). In this master thesis, the focus is to evaluate different radiolabeled targeting molecules for human epidermal growth factor receptor 2 (HER2) positive breast cancer and metastatic castration-resistant prostate cancer (mCRPC). The chosen targeting molecules are Herceptin® (trastuzumab) and PSMA-617, which will specifically target HER2- and PSMA-receptors, respectively. The HER2- and PSMA-receptors are excellent targets for use in targeted radionuclide therapy and should be explored further to achieve better and more efficient treatments than current treatments and for obtaining more personalized treatment regimens for patients. The β-emitter lutetium-177 (177Lu) has been thoroughly investigated with both trastuzumab and PSMA-617, but the use of the α-emitter actinium-225 (225Ac) is less studied with these targeting molecules. Although the 225Ac-PSMA-617 has been tested in patients, there is still a need for more knowledge about actinium-225, and a deeper understanding of the use of 225Ac in PSMA-617 and trastuzumab with regard to radiolabeling conditions, stability and their effects on cancer cells. This work has resulted in a successful synthesis of 225Ac-DOTA-trastuzumab, 225Ac-PSMA-617, [177Lu]Lu-DOTA-trastuzumab and [177Lu]Lu-PSMA-617 with high radiochemical yields (> 90 %). A new radiolabeling routine was obtained for 225Ac-PSMA-617 giving a yield of 98 % with good reproducibility. Furthermore, the stability of each radiolabeled conjugate has been thoroughly investigated and showed that all radiolabeled conjugates had a shelf-life of five days in the temperature range of 5-37 °C, except for 225Ac-DOTA-trastuzumab which only showed high stability over two days. Moreover, radiolysis effects were not observed for 225Ac-PSMA-617 samples with specific activities up to 216 kBq/µg, showing high stabilities over two weeks with approximately 90 % radiochemical purity. For 225Ac-DOTA-trastuzumab, only the samples with the lowest specific activities (< 1357 kBq/mg) were unaffected by radiolysis. The cell binding assays resulted in high cell-binding values of 94 % and 93 % for 225Ac-DOTA-trastuzumab and [177Lu]Lu-DOTA-trastuzumab on SKBR-3 cells. Furthermore, cell-binding values of 84 % and 85 % were obtained for 225Ac-PSMA-617 and [177Lu]Lu-PSMA-617 on LNCaP cells. Cell viability assays were performed and showed that 225Ac-PSMA-617 (in the range 2.5-600 Bq) is a more efficient therapeutic agent than [177Lu]Lu-PSMA-617 (in the range 50-400 kBq). The cell viability assays also confirmed that 225Ac-DOTA-trastuzumab has the potential of being a more efficient agent for the treatment of HER2-positive breast cancer than non-radioactive Herceptin®. The results of this thesis provide a significant contribution to the field of targeted alpha therapy (TAT) through studying the radiolabeling with 225Ac, the stability of 225Ac-labeled conjugates, their binding affinities and their ability to deplete cancer cells of ATP.
Rafique, Waqas; Riss, Patrick & Omtvedt, Jon Petter (2018). Synthesis of Fluorine-18 Labelled Radiotraces and Their Pre-Clinical and Clinical Characterization. Kjemisk institutt, Universitetet i Oslo. Full text in Research Archive Show summary
Positron emission tomography (PET) is one of the most sensitive in vivo imaging techniques available to clinicians and researchers. It helps in understanding the biological interactions and mechanism of various diseases through use of radiolabelled compounds called radiotracers. Herein is described the development of facile radiolabelling approaches for straightforward access to 18F-labelled trifluoromethyl radiotracers. Direct nucleophilic radiofluorination of difluorovinyl precursors was achieved for 18F-trifluoromethylation of aliphatic compounds, and applied to the radiosynthesis of [18F]lansoprazole and N-methyl[18F]lansoprazole. The compounds were used to analyze the blood-brain barrier penetration in healthy persons and for the detection of tau-neurofibrillary tangles in Alzheimer’s patients. For 18F-trifluoromethylation of aromatic compounds, in situ synthesis of Cu[18F]CF3 was achieved and used in 18F-trifluoromethylation of iodo-arenes using a single vial one-step method. The procedure was applied for radiosynthesis of a derivative of AH7921, which is a sub-type selective mu-opioid receptor agonist. The developed procedures are applicable to available radiosynthesis hardware, and provide access to desired compounds within 40 minutes in high radiochemical yields. In addition, a series of new compounds were synthesized with aim to discover the new radioligands based on modifications to the lead compounds i.e. lansoprazole and AH7921. Several interesting candidates with good combination of affinity and selectivity were identified from each series, and radiolabelled with fluorine-18. The newly developed 18F-labelled compounds have good potential to provide the in vivo characterization of tau-neurofibrillary tangles and quantification of the opioid receptors using the PET imaging.
Alluri, Santosh Reddy; Riss, Patrick & Henriksen, Gjermund (2018). Target oriented synthesis methods for imaging of proteins linked to cell-damage. University of Oslo. Full text in Research Archive
Spilhaug, Mona M.; Riss, Patrick & Schoultz, Bent Wilhelm (2017). Determination of partitioning coefficients and protein binding using high performance liquid chromatography: Towards in vitro pharmacology in radiotracer development. Universitetet i Oslo. Full text in Research Archive Show summary
We present RP-HPLC methods for the determination of the distribution coefficient at pH 7.4, as log D, and plasma protein binding. Although there are several methods available to determine distribution coefficient (log D) and protein binding, none of them involves a general and user-friendly approach that gives the opportunity to screen large libraries of compounds for both log D and plasma protein binding, with low cost and less time-consuming assays. The log D methods are amenable to rapid determinations and offer an excellent reproducibility. Standard deviation from literature was only 0.1 as an average for method A and 0.2 in method B, though method B eluted compounds earlier and worked for a broader range of complex compounds. The plasma protein binding determination made use of Microcon centrifugal filters whereas incubated test compound in porcine plasma where ultrafiltrated and the supernatant were measured by RP-HPLC. The high-throughput protocols described herein, for determination of log D and plasma protein binding, are straightforward to set up and require very small quantities of sample (< 1 mg for both lipophilicity and protein binding). In addition to the optimized methods, trends between chemical properties and lipophilicity/plasma protein binding were investigated, with no clear correlation useful for screening purposes.
Grønnevik, Gaute; Riss, Patrick & Jakobsson, Jimmy Erik (2017). Radiofluorination of amines via hypervalent iodonium (III) ylides, reduction and activating group approach. Universitetet i Oslo. Full text in Research Archive

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Published Apr. 8, 2013 2:28 PM - Last modified Oct. 20, 2020 10:31 AM