{"entity": "researcher", "timestamp": "2026-06-07T20:48:54.620Z", "family": "Velikyan", "given": "Irina", "initials": "I", "orcid": "0000-0002-3732-8857", "affiliations": [], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/947ae561cd794e5b94c6736880620287.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/947ae561cd794e5b94c6736880620287"}}, "publications": [{"entity": "publication", "iuid": "f66c6884bb7d4d93b5f39f6a68fba1a8", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/f66c6884bb7d4d93b5f39f6a68fba1a8.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/f66c6884bb7d4d93b5f39f6a68fba1a8"}}, "title": "Imaging of the Glucose-Dependent Insulinotropic Polypeptide Receptor Using a Novel Radiolabeled Peptide Rationally Designed Based on Endogenous GIP and Synthetic Exendin-4 Sequences.", "authors": [{"family": "Velikyan", "given": "Irina", "initials": "I", "orcid": "0000-0002-3732-8857", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/947ae561cd794e5b94c6736880620287.json"}}, {"family": "Bossart", "given": "Martin", "initials": "M"}, {"family": "Haack", "given": "Torsten", "initials": "T"}, {"family": "Laitinen", "given": "Iina", "initials": "I"}, {"family": "Estrada", "given": "Sergio", "initials": "S"}, {"family": "Johansson", "given": "Lars", "initials": "L"}, {"family": "Pierrou", "given": "Stefan", "initials": "S"}, {"family": "Wagner", "given": "Michael", "initials": "M"}, {"family": "Eriksson", "given": "Olof", "initials": "O", "orcid": "0000-0002-2515-8790", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/85991bf00e4b4a26ab15599d25c58601.json"}}], "type": "journal article", "published": "2022-12-31", "journal": {"title": "Pharmaceuticals (Basel, Switzerland)", "issn": "1424-8247", "volume": "16", "issue": "1", "issn-l": "1424-8247"}, "abstract": "Imaging and radiotherapy targeting the glucose-dependent insulinotropic polypeptide receptor (GIPR) could potentially benefit the management of neuroendocrine neoplasms (NENs), complementing clinically established radiopharmaceuticals. The aim of this study was to evaluate a GIPR-targeting positron emission tomography (PET) radioligand with receptor-specific binding, fast blood clearance, and low liver background uptake. The peptide DOTA-bioconjugate, C803-GIP, was developed based on the sequence of the endogenous GIP(1-30) and synthetic exendin-4 peptides with selective amino acid mutations to combine their specificity for the GIPR and in vivo stability, respectively. The 68Ga-labeled bioconjugate was evaluated in vitro in terms of binding affinity, specificity, and internalization in HEK293 cells transfected with the human GIPR, GLP1, or GCG receptors and in sections of human insulinoma and NENs. In vivo binding specificity, biodistribution, and tissue background were investigated in mice bearing huGIPR-HEK293 xenografts and in a pig. Ex vivo organ distribution, pharmacokinetics, and dosimetry were studied in normal rats. [68Ga]Ga-C803-GIP was stable and demonstrated a high affinity to the huGIPR-HEK293 cells. Binding specificity was demonstrated in vitro in frozen sections of NENs and huGIPR-HEK293 cells. No specific uptake was observed in the negative controls of huGLP1R and huGCGR cells. A novel rationally designed PET radioligand, [68Ga]Ga-C803-GIP, demonstrated promising binding characteristics and specificity towards the GIPR.", "doi": "10.3390/ph16010061", "pmid": "36678558", "labels": {"SciLifeLab Fellow": null, "Olof Eriksson": null}, "xrefs": [{"db": "pmc", "key": "PMC9864903"}, {"db": "pii", "key": "ph16010061"}], "notes": [], "created": "2023-05-14T14:51:58.692Z", "modified": "2023-05-14T14:51:58.707Z"}, {"entity": "publication", "iuid": "42e4a478a1c54d75a770584391e33cbf", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/42e4a478a1c54d75a770584391e33cbf.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/42e4a478a1c54d75a770584391e33cbf"}}, "title": "Improved Radiolytic Stability of a 68Ga-labelled Collagelin Analogue for the Imaging of Fibrosis.", "authors": [{"family": "Velikyan", "given": "Irina", "initials": "I", "orcid": "0000-0002-3732-8857", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/947ae561cd794e5b94c6736880620287.json"}}, {"family": "Rosenstr\u00f6m", "given": "Ulrika", "initials": "U", "orcid": "0000-0002-0817-8140", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ec6820fcb786475d85969630b0b3860b.json"}}, {"family": "Rosestedt", "given": "Maria", "initials": "M"}, {"family": "Eriksson", "given": "Olof", "initials": "O", "orcid": "0000-0002-2515-8790", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/85991bf00e4b4a26ab15599d25c58601.json"}}, {"family": "Antoni", "given": "Gunnar", "initials": "G"}], "type": "journal article", "published": "2021-09-28", "journal": {"title": "Pharmaceuticals (Basel, Switzerland)", "issn": "1424-8247", "volume": "14", "issue": "10", "issn-l": "1424-8247"}, "abstract": "There is an unmet medical need for non-invasive, sensitive, and quantitative methods for the assessment of fibrosis. Herein, an improved collagelin analogue labelled with gallium-68 for use with positron emission tomography (PET) is presented. A cyclic peptide, c[CPGRVNleHGLHLGDDEGPC], was synthesized by solid-phase peptide synthesis, conjugated to 2-(4,7-bis(2-(tert-butoxy)-2-oxoethyl)-1,4,7-triazonan-1-yl)acetic acid, and labelled with gallium-68. High performance liquid chromatography (HPLC) was used for the quality and stability assessment of the collagelin analogue. Non-specific organ distribution, blood clearance, and excretion rates were investigated in healthy mice and rats using ex vivo organ distribution analysis and dynamic in vivo PET/CT. Mice with carbon tetrachloride (CCl4) induced liver fibrosis were used for the investigation of specific binding via in vitro frozen section autoradiography, ex vivo organ distribution, and in vivo PET/CT. A non-decay corrected radiochemical yield (48 \u00b1 6%) of [68Ga]Ga-NOTA-PEG2-c[CPGRVNleHGLHLGDDEGPC] ([68Ga]Ga-NO2A-[Nle13]-Col) with a radiochemical purity of 98 \u00b1 2% was achieved without radical scavengers. The 68Ga-labelling was regioselective and stable at ambient temperature for at least 3 h. The autoradiography of the cryosections of fibrotic mouse liver tissue demonstrated a distinct heterogeneous radioactivity uptake that correlated with the fibrosis scores estimated after Sirius Red staining. The blood clearance and tissue washout from the [68Ga]Ga-NO2A-[Nle13]-Col was fast in both normal and diseased mice. Dosimetry investigation in rats indicated the possibility for 4-5 PET/CT examinations per year. Radiolytic stability of the collagelin analogue was achieved by the substitution of methionine with norleucine amino acid residue without a deterioration of its binding capability. [68Ga]Ga-NO2A-[Nle13]-Col demonstrated a safe dosimetry profile suitable for repeated scanning.", "doi": "10.3390/ph14100990", "pmid": "34681214", "labels": {"SciLifeLab Fellow": null, "Olof Eriksson": null}, "xrefs": [{"db": "pmc", "key": "PMC8537947"}, {"db": "pii", "key": "ph14100990"}], "notes": [], "created": "2023-05-14T14:52:50.511Z", "modified": "2023-05-14T14:52:50.576Z"}, {"entity": "publication", "iuid": "c42939b0c7544f54a8c300cba1d803fc", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/c42939b0c7544f54a8c300cba1d803fc.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/c42939b0c7544f54a8c300cba1d803fc"}}, "title": "Automated GMP-Compliant Production of [68Ga]Ga-DO3A-Tuna-2 for PET Microdosing Studies of the Glucagon Receptor in Humans.", "authors": [{"family": "Wagner", "given": "Michael", "initials": "M"}, {"family": "Doverfjord", "given": "Johan G", "initials": "JG"}, {"family": "Tillner", "given": "Joachim", "initials": "J", "orcid": "0000-0002-2798-2732", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5620bf0076664fd280498b362b410ea7.json"}}, {"family": "Antoni", "given": "Gunnar", "initials": "G"}, {"family": "Haack", "given": "Torsten", "initials": "T"}, {"family": "Bossart", "given": "Martin", "initials": "M"}, {"family": "Laitinen", "given": "Iina", "initials": "I"}, {"family": "Johansson", "given": "Lars", "initials": "L"}, {"family": "Pierrou", "given": "Stefan", "initials": "S"}, {"family": "Eriksson", "given": "Olof", "initials": "O"}, {"family": "Velikyan", "given": "Irina", "initials": "I", "orcid": "0000-0002-3732-8857", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/947ae561cd794e5b94c6736880620287.json"}}], "type": "journal article", "published": "2020-07-31", "journal": {"title": "Pharmaceuticals (Basel, Switzerland)", "issn": "1424-8247", "issn-l": "1424-8247", "volume": "13", "issue": "8", "pages": "176"}, "abstract": "Introduction: [68Ga]Ga-DO3A-VS-Cys40-Tuna-2 (previously published as [68Ga]Ga-DO3A-VS-Cys40-S01-GCG) has shown high-affinity specific binding to the glucagon receptor (GCGR) in vitro and in vivo in rats and non-human primates in our previous studies, confirming the suitability of the tracer for drug development applications in humans. The manufacturing process of [68Ga]Ga-DO3A-VS-Cys40-Tuna-2 was automated for clinical use to meet the radiation safety and good manufacturing practice (GMP) requirements. Methods: The automated synthesis platform (Modular-Lab PharmTrace, Eckert & Ziegler, Eurotope, Germany), disposable cassettes for 68Ga-labeling, and pharmaceutical-grade 68Ge/68Ga generator (GalliaPharm\u00ae) used in the study were purchased from Eckert & Ziegler. The parameters such as time, temperature, precursor concentration, radical scavenger, buffer concentration, and pH, as well as product purification step, were investigated and optimized. Process optimization was conducted with regard to product quality and quantity, as well as process reproducibility. The active pharmaceutical ingredient starting material DO3A-VS-Cys40-Tuna-2 (GMP-grade) was provided by Sanofi Aventis. Results: The reproducible and GMP-compliant automated production of [68Ga]Ga-DO3A-VS-Cys40-Tuna-2 with on-line documentation was developed. The non-decay-corrected radiochemical yield was 45.2 \u00b1 2.5% (n = 3, process validation) at the end of the synthesis with a labeling synthesis duration of 38 min and a quality controlincluding release procedure of 20 min. The radiochemical purity of the product was 98.9 \u00b1 0.6% (n = 17) with the total amount of the peptide in the preparation of 48 \u00b1 2 \u00b5g (n = 3, process validation). Radionuclidic purity, sterility, endotoxin content, residual solvent content, and sterile filter integrity tests met the acceptance criteria. The product was stable at ambient temperature for at least 2 h. Conclusion: The fully automated GMP-compliant manufacturing process was developed and thoroughly validated. The resulting [68Ga]Ga-DO3A-VS-Cys40-Tuna-2 was used in a clinical study for accurate quantification of GCGR occupancy by a dual anti-diabetic drug in vivo in humans.", "doi": "10.3390/ph13080176", "pmid": "32752075", "labels": {"Olof Eriksson": null, "SciLifeLab Fellow": null}, "xrefs": [{"db": "pmc", "key": "PMC7463542"}, {"db": "pii", "key": "ph13080176"}], "notes": [], "created": "2020-11-07T06:55:22.554Z", "modified": "2023-05-14T14:54:07.830Z"}, {"entity": "publication", "iuid": "6db3212b9fdd427db2b8bd9c04da1e54", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/6db3212b9fdd427db2b8bd9c04da1e54.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/6db3212b9fdd427db2b8bd9c04da1e54"}}, "title": "Fully automated GMP production of [68Ga]Ga-DO3A-VS-Cys40-Exendin-4 for clinical use.", "authors": [{"family": "Velikyan", "given": "Irina", "initials": "I", "orcid": "0000-0002-3732-8857", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/947ae561cd794e5b94c6736880620287.json"}}, {"family": "Rosenstrom", "given": "Ulrika", "initials": "U", "orcid": "0000-0002-0817-8140", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ec6820fcb786475d85969630b0b3860b.json"}}, {"family": "Eriksson", "given": "Olof", "initials": "O", "orcid": "0000-0002-2515-8790", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/85991bf00e4b4a26ab15599d25c58601.json"}}], "type": "journal article", "published": "2017-07-15", "journal": {"title": "American journal of nuclear medicine and molecular imaging", "issn": "2160-8407", "volume": "7", "issue": "3", "pages": "111-125", "issn-l": "2160-8407"}, "abstract": "[68Ga]Ga-DO3A-VS-Cys40-Exendin-4/PET-CT targeting glucagon like peptide-1 receptor (GLP-1R) has previously demonstrated its potential clinical value for the detection of insulinomas. The production and accessibility of this radiopharmaceutical is one of the critical factors in realization of clinical trials and routine clinical examinations. Previously, the radiopharmaceutical was prepared manually, however larger scale of clinical trials and healthcare requires automation of the production process in order to limit the operator radiation dose as well as improve tracer manufacturing robustness and on-line documentation for enhanced good manufacturing practice (GMP) compliance. A method for 68Ga-labelling of DO3A-VS-Cys40-Exendin-4 on a commercially available synthesis platform was developed. Equipment such as 68Ge/68Ga generator, synthesis platform, and disposable cassettes for 68Ga-labelling used in the study was purchased from Eckert & Ziegler. DO3A-VS-Cys40-Exendin-4 was synthesized in-house. The parameters such as time, temperature, precursor concentration, radical scavenger, buffer concentration, pH, product purification step were investigated and optimised. Reproducible and GMP compliant automated production of [68Ga]Ga-DO3A-VS-Cys40-Exendin-4 was developed. Exendin-4 comprising methionine amino acid residue was prone to oxidation which was strongly influenced by the elevated temperature, radioactivity amount, and precursor concentration. The suppression of the oxidative radiolysis was achieved by addition of ethanol, dihydroxybenzoic acid and ascorbic acid to the reaction buffer as well as by optimizing heating temperature. The non-decay corrected radiochemical yield was 43\u00b12% with radiochemical purity of over 90% wherein the individual impurity signals in HPLC chromatogram did not exceed 5%. Automated production and quality control methods were established for paving the pathway for broader clinical use of [68Ga]Ga-DO3A-VS-Cys40-Exendin-4.", "doi": null, "pmid": "28721305", "labels": {"Olof Eriksson": null, "SciLifeLab Fellow": null}, "xrefs": [{"db": "pmc", "key": "PMC5511121"}], "notes": [], "created": "2020-10-06T13:46:24.015Z", "modified": "2025-11-17T09:17:17.057Z"}, {"entity": "publication", "iuid": "828640fda961421082598ddb6c3a6cc6", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/828640fda961421082598ddb6c3a6cc6.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/828640fda961421082598ddb6c3a6cc6"}}, "title": "Dosimetry of [(68)Ga]Ga-DO3A-VS-Cys(40)-Exendin-4 in rodents, pigs, non-human primates and human - repeated scanning in human is possible.", "authors": [{"family": "Selvaraju", "given": "Ram Kumar", "initials": "RK"}, {"family": "Bulenga", "given": "Thomas N", "initials": "TN"}, {"family": "Espes", "given": "Daniel", "initials": "D", "orcid": "0000-0001-8843-7941", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/80736c5043194099992841a2a2a161f9.json"}}, {"family": "Lubberink", "given": "Mark", "initials": "M", "orcid": "0000-0001-8324-7399", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e8c1d9a8e08a40d3b7a694fd293c2400.json"}}, {"family": "S\u00f6rensen", "given": "Jens", "initials": "J"}, {"family": "Eriksson", "given": "Barbro", "initials": "B"}, {"family": "Estrada", "given": "Sergio", "initials": "S"}, {"family": "Velikyan", "given": "Irina", "initials": "I", "orcid": "0000-0002-3732-8857", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/947ae561cd794e5b94c6736880620287.json"}}, {"family": "Eriksson", "given": "Olof", "initials": "O", "orcid": "0000-0002-2515-8790", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/85991bf00e4b4a26ab15599d25c58601.json"}}], "type": "journal article", "published": "2015-02-15", "journal": {"title": "American journal of nuclear medicine and molecular imaging", "issn": "2160-8407", "volume": "5", "issue": "3", "pages": "259-269", "issn-l": "2160-8407"}, "abstract": "Quantitative PET imaging with [(68)Ga]Ga-DO3A-VS-Cys(40)-Exendin-4 has potential use in diabetes and cancer. However, the radiation dose to the kidneys has been a concern for the possibility of repeated imaging studies in humans. Therefore, we investigated the dosimetry of [(68)Ga]Ga-DO3A-VS-Cys(40)-Exendin-4 based on the biodistribution data in rats, pigs, non-human primates (NHP) and a human.Organ distribution of [(68)Ga]Ga-DO3A-VS-Cys(40)-Exendin-4 in rats (Male Lewis; n=12; 30, 60, and 80 min) was measured ex vivo. The dynamic uptake of [(68)Ga]Ga-DO3A-VS-Cys(40)-Exendin-4 in the abdomen was assessed by PET/CT scanning of pigs (male; n = 4, 0-60 min), NHP (Female; cynomolgus; n=3; 0-90 min), and human (female; n=1; 0-40, 100, 120 min).The organ distribution data in each species were extrapolated to those of a human, assuming similar distribution between the species. Residence times were assessed by trapezoidal approximation of the kinetic data. Organ doses (mGy/MBq) and the whole body effective dose (mSv/MBq), was extrapolated by using the OLINDA/EXM 1.1 software. The extrapolated human whole body effective dose was 0.017 \u00b1 0.004 (rats), 0.014 \u00b1 0.004 (pigs), 0.017 \u00b1 0.004 (NHP), and 0.016 (human) mSv/MBq. The absorbed dose to the kidneys was limiting:0.33 \u00b1 0.06 (rats), 0.28\u00b10.05 (pigs), 0.65 \u00b1 0.11 (NHP), and 0.28 (human) mGy/MBq, which corresponded to the maximum yearly administered amounts of 455 (rat), 536 (pig), 231 (NHP), and 536 (human) MBq before reaching the yearly kidney limiting dose of 150 mGy. More than 200 MBq of [(68)Ga]Ga-DO3A-VS-Cys(40)-Exendin-4 can be administered yearly in a human, allowing for repeated (2-4 times) scanning. This potentially enables longitudinal clinical PET imaging studies of the GLP-1R in the pancreas, transplanted islets, or insulinoma.", "doi": null, "pmid": "26069859", "labels": {"Olof Eriksson": null, "SciLifeLab Fellow": null}, "xrefs": [{"db": "pmc", "key": "PMC4446394"}], "notes": [], "created": "2020-10-06T13:53:32.732Z", "modified": "2025-11-17T09:33:25.651Z"}, {"entity": "publication", "iuid": "23dafd499e534eac8f4d0a3f9f349a00", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/23dafd499e534eac8f4d0a3f9f349a00.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/23dafd499e534eac8f4d0a3f9f349a00"}}, "title": "Preparation and evaluation of (68)Ga-DOTA-hEGF for visualization of EGFR expression in malignant tumors.", "authors": [{"family": "Velikyan", "given": "Irina", "initials": "I", "orcid": "0000-0002-3732-8857", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/947ae561cd794e5b94c6736880620287.json"}}, {"family": "Sundberg", "given": "Asa Liljegren", "initials": "AL"}, {"family": "Lindhe", "given": "Orjan", "initials": "O"}, {"family": "H\u00f6glund", "given": "A Urban", "initials": "AU"}, {"family": "Eriksson", "given": "Olof", "initials": "O", "orcid": "0000-0002-2515-8790", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/85991bf00e4b4a26ab15599d25c58601.json"}}, {"family": "Werner", "given": "Eva", "initials": "E"}, {"family": "Carlsson", "given": "Jorgen", "initials": "J", "orcid": "0000-0003-4623-2977", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/792c1cd4aca248dc94b967115ffa82df.json"}}, {"family": "Bergstr\u00f6m", "given": "Mats", "initials": "M"}, {"family": "L\u00e5ngstr\u00f6m", "given": "Bengt", "initials": "B"}, {"family": "Tolmachev", "given": "Vladimir", "initials": "V"}], "type": "evaluation study", "published": "2005-11-00", "journal": {"title": "Journal of nuclear medicine : official publication, Society of Nuclear Medicine", "issn": "0161-5505", "volume": "46", "issue": "11", "pages": "1881-1888", "issn-l": null}, "abstract": "Detection of epidermal growth factor receptor (EGFR) overexpression in many carcinomas provides important diagnostic information, which can influence patient management. The use of PET may enable such detection in vivo by a noninvasive procedure with high sensitivity. The aim of this study was to develop a method for preparation of a positron-emitting tracer based on a natural ligand to EGFR, the recombinant human epidermal growth factor (hEGF), and to perform a preclinical evaluation of the tracer.\n\nDOTA-hEGF (DOTA is 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid) was prepared by coupling of a N-sulfosuccinimide ester of DOTA to hEGF. The conjugate was labeled with a generator-produced positron-emitting nuclide, (68)Ga (half-life = 68 min), using microwave heating. Binding specificity, affinity, internalization, and retention of (68)Ga-DOTA-hEGF was studied in 2 EGFR-expressing cell lines, U343 glioma cells and A431 cervical carcinoma cells. Biodistribution and microPET visualization studies were performed in BALB/c nu/nu mice bearing A431 carcinoma xenografts.\n\nA 1-min-long microwave-assisted labeling provided radioactivity incorporation of 77% +/- 4%. Both cell lines demonstrated receptor-specific uptake of the conjugate, rapid internalization of the tracer, and good retention of radioactivity. Binding to both cell lines occurred with high affinity, approximately 2 nmol/L. The biodistribution study demonstrated accumulation of radioactivity in xenografts and in EGFR-expressing organs. The microPET imaging study enabled visualization of tumors and demonstrated quick--within 5 min--localization of radioactivity in tumors.\n\n(68)Ga-DOTA-hEGF has potential for imaging EGFR overexpression in tumors.", "doi": null, "pmid": "16269603", "labels": {"Olof Eriksson": null, "SciLifeLab Fellow": null}, "xrefs": [{"db": "pii", "key": "46/11/1881"}], "notes": [], "created": "2020-10-06T14:12:38.035Z", "modified": "2025-11-17T09:14:34.656Z"}]}