{"entity": "researcher", "timestamp": "2026-08-22T08:30:20.517Z", "family": "Kanellopoulos", "given": "Panagiotis", "initials": "P", "orcid": "0000-0002-0617-3936", "affiliations": ["Department of Medicinal Chemistry, Uppsala University, 752 37 Uppsala, Sweden."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/85ce3df2ffae4754946f11bb2e98ef97.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/85ce3df2ffae4754946f11bb2e98ef97"}}, "publications": [{"entity": "publication", "iuid": "612efa2811274e2596fcccfca71c1d4c", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/612efa2811274e2596fcccfca71c1d4c.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/612efa2811274e2596fcccfca71c1d4c"}}, "title": "Evaluation of ABD-Linked RM26 Conjugates for GRPR-Targeted Drug Delivery.", "authors": [{"family": "Nagy", "given": "\u00c1bel", "initials": "\u00c1"}, {"family": "Abouzayed", "given": "Ayman", "initials": "A"}, {"family": "Kanellopoulos", "given": "Panagiotis", "initials": "P", "orcid": "0000-0002-0617-3936", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/85ce3df2ffae4754946f11bb2e98ef97.json"}}, {"family": "Landmark", "given": "Fredrika", "initials": "F"}, {"family": "Bezverkhniaia", "given": "Ekaterina", "initials": "E"}, {"family": "Tolmachev", "given": "Vladimir", "initials": "V"}, {"family": "Orlova", "given": "Anna", "initials": "A", "orcid": "0000-0001-6120-2683", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1c374f429702489494c05f84f298b4b7.json"}}, {"family": "Eriksson Karlstr\u00f6m", "given": "Amelie", "initials": "A", "orcid": "0000-0002-0695-5188", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/084ac56a883542f0b79ac6f63a9d6b1d.json"}}], "type": "journal article", "published": "2024-08-27", "journal": {"title": "ACS Omega", "issn": "2470-1343", "volume": "9", "issue": "34", "pages": "36122-36133", "issn-l": "2470-1343"}, "abstract": "Targeting the gastrin-releasing peptide receptor (GRPR) with the bombesin analogue RM26, a 9 aa peptide, has been a promising strategy for cancer theranostics, with recent success in radionuclide imaging of prostate cancer. However, therapeutic application of the short peptide RM26 would require a longer half-life to prevent fast clearance from the circulation. Conjugation to an albumin-binding domain (ABD) is a viable strategy to extend the in vivo half-life of peptides and proteins. We previously reported an ABD-fused RM26 peptide targeting GRPR (ABD-RM26 Gen 1) that showed prolonged and stable tumor uptake over 144 h; however, the observed high kidney uptake indicated that the conjugate's binding to albumin was reduced and that this could be an obstacle for its use as a delivery system for targeted therapy, especially for radiotherapy. Here, we have designed, produced, and preclinically evaluated a series of novel ABD-RM26 conjugates with the aim of improving the conjugate's binding to albumin and decreasing the kidney uptake. We developed three second-generation constructs with varying formats, differing in the relative positions of the targeting moieties and the radionuclide chelator. The produced conjugates were radiolabeled with indium-111 and evaluated in vitro and in vivo. All constructs displayed improved biophysical characteristics, biodistribution, and lower kidney uptake compared to previously reported first-generation molecules. The ABD-RM26 Gen 2A conjugate showed the best biodistribution profile with a nearly 6-fold reduction in kidney uptake. However, the ABD-RM26 Gen 2A conjugate's binding to GRPR was compromised. This conjugate's assembly of albumin- and GRPR-binding moieties might be used for further development of drug conjugates for targeted therapy/radiotherapy of GRPR-expressing cancers.", "doi": "10.1021/acsomega.4c00489", "pmid": "39220525", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC11359615"}], "notes": [], "created": "2026-08-21T11:36:49.821Z", "modified": "2026-08-21T11:36:49.966Z"}, {"entity": "publication", "iuid": "90c487922a1047ee8f5a09c2f53c2d41", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/90c487922a1047ee8f5a09c2f53c2d41.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/90c487922a1047ee8f5a09c2f53c2d41"}}, "title": "Two Novel [68Ga]Ga-Labeled Radiotracers Based on Metabolically Stable [Sar11]RM26 Antagonistic Peptide for Diagnostic Positron Emission Tomography Imaging of GRPR-Positive Prostate Cancer.", "authors": [{"family": "Kanellopoulos", "given": "Panagiotis", "initials": "P", "orcid": "0000-0002-0617-3936", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/85ce3df2ffae4754946f11bb2e98ef97.json"}}, {"family": "Bezverkhniaia", "given": "Ekaterina", "initials": "E"}, {"family": "Abouzayed", "given": "Ayman", "initials": "A"}, {"family": "Rosenstr\u00f6m", "given": "Ulrika", "initials": "U", "orcid": "0000-0002-0817-8140", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ec6820fcb786475d85969630b0b3860b.json"}}, {"family": "Tolmachev", "given": "Vladimir", "initials": "V"}, {"family": "Orlova", "given": "Anna", "initials": "A", "orcid": "0000-0001-6120-2683", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1c374f429702489494c05f84f298b4b7.json"}}], "type": "journal article", "published": "2024-04-23", "journal": {"title": "ACS Omega", "issn": "2470-1343", "volume": "9", "issue": "16", "pages": "18608-18616", "issn-l": "2470-1343"}, "abstract": "Gastrin releasing peptide receptor (GRPR) is overexpressed in prostate cancer (PC-3) and can be used for diagnostic purposes. We herein present the design and preclinical evaluation of two novel NOTA/NODAGA-containing peptides suitable for labeling with the positron emission tomography (PET) radionuclide Ga-68. These analogs are based on the previously reported GRPR-antagonist DOTAGA-PEG2-[Sar11]RM26, developed for targeted radiotheraostic applications. Both NOTA-PEG2-[Sar11]RM26 and NODAGA-PEG2-[Sar11]RM26 were successfully labeled with Ga-68 and evaluated in vitro and in vivo using PC-3 cell models. Both, [68Ga]Ga-NOTA-PEG2-[Sar11]RM26 and [68Ga]Ga-NODAGA-PEG2-[Sar11]RM26 displayed high metal-chelate stability in phosphate buffered saline and against the EDTA-challenge. The two [68Ga]Ga-labeled conjugates demonstrated highly GRPR-mediated uptake in vitro and in vivo and exhibited a slow internalization over time, typical for radioantagonistis. The [natGa]Ga-loaded peptides displayed affinity in the low nanomole range for GRPR in competition binding experiments. The new radiotracers demonstrated biodistribution profiles suitable for diagnostic imaging shortly after administration with fast background clearance. Their high tumor uptake (13 \u00b1 1 and 15 \u00b1 3% IA/g for NOTA and NODAGA conjugates, respectively) and high tumor-to-blood ratios (60 \u00b1 10 and 220 \u00b1 70, respectively) 3 h pi renders them promising PET tracers for use in patients. Tumor-to-normal organ ratios were higher for [68Ga]Ga-NODAGA-PEG2-[Sar11]RM26 than for the NOTA-containing counterpart. The performance of the two radiopeptides was further supported with the PET/CT images. In conclusion, [68Ga]Ga-NODAGA-PEG2-[Sar11]RM26 is a promising PET imaging tracer for visualization of GRPR-expressing lesions with high imaging contrast shortly after administration.", "doi": "10.1021/acsomega.4c01348", "pmid": "38680331", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC11044165"}], "notes": [], "created": "2026-08-21T11:36:52.055Z", "modified": "2026-08-21T11:36:52.088Z"}, {"entity": "publication", "iuid": "9f6b8e882b61420687b18816fd59c8fe", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/9f6b8e882b61420687b18816fd59c8fe.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/9f6b8e882b61420687b18816fd59c8fe"}}, "title": "GRPR-Antagonists Carrying DOTAGA-Chelator via Positively Charged Linkers: Perspectives for Prostate Cancer Theranostics.", "authors": [{"family": "Obeid", "given": "Karim", "initials": "K"}, {"family": "Kanellopoulos", "given": "Panagiotis", "initials": "P", "orcid": "0000-0002-0617-3936", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/85ce3df2ffae4754946f11bb2e98ef97.json"}}, {"family": "Abouzayed", "given": "Ayman", "initials": "A"}, {"family": "Mattsson", "given": "Adam", "initials": "A"}, {"family": "Tolmachev", "given": "Vladimir", "initials": "V", "orcid": "0000-0002-6122-1734", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/896ae9fae8b74251afe11b4354c62794.json"}}, {"family": "Nock", "given": "Berthold A", "initials": "BA", "orcid": "0000-0002-6028-9112", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/58c006b61c854f2f8e61b2ddb0d21096.json"}}, {"family": "Maina", "given": "Theodosia", "initials": "T", "orcid": "0000-0002-1123-2486", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b43f747494e64e9cacf77979cdbaf0a6.json"}}, {"family": "Orlova", "given": "Anna", "initials": "A", "orcid": "0000-0001-6120-2683", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1c374f429702489494c05f84f298b4b7.json"}}], "type": "journal article", "published": "2024-04-08", "journal": {"title": "Pharmaceutics", "issn": "1999-4923", "volume": "16", "issue": "4", "issn-l": null}, "abstract": "Gastrin-releasing peptide receptor (GRPR)-antagonists have served as motifs in the development of theranostic radioligands for prostate cancer. Our efforts have been focused on the development of radiolabeled RM26 (H-DPhe6-Gln7-Trp8-Ala9-Val10-Gly11-His12-Sta13-Leu14-NH2) analogs, such as [111In]In-DOTAGA-PEG2-RM26. We recently showed that its Gly11/Sar11-substituted version, [111In]In-AU-RM26-M1, resisted degradation by neprilysin (NEP) while in circulation and achieved higher tumor uptake in mice. We herein introduce the following three new AU-RM26-M1 mimics labeled with In-111, with basic residues in the linker: (i) AU-RM26-M2 (PEG2-Pip), (ii) AU-RM26-M3 (PEG2-Arg), and (iii) AU-RM26-M4 (Arg-Arg-Pip). These analogs were compared in PC-3 cells and animal models vs. AU-RM26-M1 (reference). The new analogs showed high affinity and specificity for the GRPR, exhibiting an uptake and distribution pattern in PC-3 cells typical for a radiolabeled GRPR-antagonist. They showed high stability in peripheral mice blood, except for [111In]In-AU-RM26-M3. AU-RM26-M4 achieved the highest tumor uptake and promising background clearance, followed by [111In]In-RM26-M2, showing lower background levels. These findings were confirmed for [111In]In-AU-RM26-M2 and [111In]In-AU-RM26-M4 by micro-SPECT/CT at 4 and 24 h post-injection. Hence, the type of positively charged residues in the linker of AU-RM26-M1 mimics strongly influenced biological behavior. The analogs with Pip next to DPhe6 demonstrated the best overall characteristics and warrant further investigation.", "doi": "10.3390/pharmaceutics16040513", "pmid": "38675174", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC11054746"}, {"db": "pii", "key": "pharmaceutics16040513"}], "notes": [], "created": "2026-08-21T13:05:03.776Z", "modified": "2026-08-21T13:05:03.852Z"}, {"entity": "publication", "iuid": "686e6e55613a4b12ace642daaf877885", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/686e6e55613a4b12ace642daaf877885.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/686e6e55613a4b12ace642daaf877885"}}, "title": "Influence of Molecular Design on the Tumor Targeting and Biodistribution of PSMA-Binding Tracers Labeled with Technetium-99m.", "authors": [{"family": "Bezverkhniaia", "given": "Ekaterina", "initials": "E", "orcid": "0000-0001-7699-5719", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/211d24252bc84d43aed1d7ed4c3d3238.json"}}, {"family": "Kanellopoulos", "given": "Panagiotis", "initials": "P", "orcid": "0000-0002-0617-3936", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/85ce3df2ffae4754946f11bb2e98ef97.json"}}, {"family": "Rosenstr\u00f6m", "given": "Ulrika", "initials": "U", "orcid": "0000-0002-0817-8140", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ec6820fcb786475d85969630b0b3860b.json"}}, {"family": "Tolmachev", "given": "Vladimir", "initials": "V", "orcid": "0000-0002-6122-1734", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/896ae9fae8b74251afe11b4354c62794.json"}}, {"family": "Orlova", "given": "Anna", "initials": "A", "orcid": "0000-0001-6120-2683", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1c374f429702489494c05f84f298b4b7.json"}}], "type": "journal article", "published": "2024-03-23", "journal": {"title": "Int J Mol Sci", "issn": "1422-0067", "volume": "25", "issue": "7", "issn-l": null}, "abstract": "Previously, we designed the EuK-based PSMA ligand BQ0413 with an maE3 chelator for labeling with technetium-99m. It showed efficient tumor targeting, but our preclinical data and preliminary clinical results indicated that the renal excretion levels need to be decreased. We hypothesized that this could be achieved by a decrease in the ligand's total negative charge, achieved by substituting negatively charged glutamate residues in the chelator with glycine. The purpose of this study was to evaluate the tumor targeting and biodistribution of two new PSMA inhibitors, BQ0411 and BQ0412, compared to BQ0413. Conjugates were radiolabeled with Tc-99m and characterized in vitro, using PC3-pip cells, and in vivo, using NMRI and PC3-pip tumor-bearing mice. [99mTc]Tc-BQ0411 and [99mTc]Tc-BQ0412 demonstrated PSMA-specific binding to PC3-pip cells with picomolar affinity. The biodistribution pattern for the new conjugates was characterized by rapid excretion. The tumor uptake for [99mTc]Tc-BQ0411 was 1.6-fold higher compared to [99mTc]Tc-BQ0412 and [99mTc]Tc-BQ0413. [99mTc]Tc-BQ0413 has demonstrated predominantly renal excretion, while the new conjugates underwent both renal and hepatobiliary excretion. In this study, we have demonstrated that in such small targeting ligands as PSMA-binding EuK-based pseudopeptides, the structural blocks that do not participate in binding could have a crucial role in tumor targeting and biodistribution. The presence of a glycine-based coupling linker in BQ0411 and BQ0413 seems to optimize biodistribution. In conclusion, the substitution of amino acids in the chelating sequence is a promising method to alter the biodistribution of [99mTc]Tc-labeled small-molecule PSMA inhibitors. Further improvement of the biodistribution properties of BQ0413 is needed.", "doi": "10.3390/ijms25073615", "pmid": "38612427", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC11011439"}, {"db": "pii", "key": "ijms25073615"}], "notes": [], "created": "2026-08-21T13:03:53.276Z", "modified": "2026-08-21T13:03:53.348Z"}, {"entity": "publication", "iuid": "8dd62b52564244adb5b31b41d3dad8c8", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/8dd62b52564244adb5b31b41d3dad8c8.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/8dd62b52564244adb5b31b41d3dad8c8"}}, "title": "Preclinical Evaluation of a Novel High-Affinity Radioligand [99mTc]Tc-BQ0413 Targeting Prostate-Specific Membrane Antigen (PSMA).", "authors": [{"family": "Bezverkhniaia", "given": "Ekaterina", "initials": "E", "orcid": "0000-0001-7699-5719", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/211d24252bc84d43aed1d7ed4c3d3238.json"}}, {"family": "Kanellopoulos", "given": "Panagiotis", "initials": "P", "orcid": "0000-0002-0617-3936", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/85ce3df2ffae4754946f11bb2e98ef97.json"}}, {"family": "Abouzayed", "given": "Ayman", "initials": "A"}, {"family": "Larkina", "given": "Mariia", "initials": "M", "orcid": "0000-0003-1176-2441", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/557c8a9c8b2142a7a88d6211335d24e4.json"}}, {"family": "Oroujeni", "given": "Maryam", "initials": "M", "orcid": "0000-0003-2660-9837", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8bdd7a76401c42b4bbe8b11cfdb83212.json"}}, {"family": "Vorobyeva", "given": "Anzhelika", "initials": "A", "orcid": "0000-0002-4778-3909", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/99703faa11ab4c19aff2f426f61c3134.json"}}, {"family": "Rosenstr\u00f6m", "given": "Ulrika", "initials": "U", "orcid": "0000-0002-0817-8140", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ec6820fcb786475d85969630b0b3860b.json"}}, {"family": "Tolmachev", "given": "Vladimir", "initials": "V", "orcid": "0000-0002-6122-1734", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/896ae9fae8b74251afe11b4354c62794.json"}}, {"family": "Orlova", "given": "Anna", "initials": "A", "orcid": "0000-0001-6120-2683", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1c374f429702489494c05f84f298b4b7.json"}}], "type": "journal article", "published": "2023-12-12", "journal": {"title": "Int J Mol Sci", "issn": "1422-0067", "volume": "24", "issue": "24", "issn-l": null}, "abstract": "Radionuclide imaging using radiolabeled inhibitors of prostate-specific membrane antigen (PSMA) can be used for the staging of prostate cancer. Previously, we optimized the Glu-urea-Lys binding moiety using a linker structure containing 2-napththyl-L-alanine and L-tyrosine. We have now designed a molecule that contains mercaptoacetyl-triglutamate chelator for labeling with Tc-99m (designated as BQ0413). The purpose of this study was to evaluate the imaging properties of [99mTc]Tc-BQ0413. PSMA-transfected PC3-pip cells were used to evaluate the specificity and affinity of [99mTc]Tc-BQ0413 binding in vitro. PC3-pip tumor-bearing BALB/C nu/nu mice were used as an in vivo model. [99mTc]Tc-BQ0413 bound specifically to PC3-pip cells with an affinity of 33 \u00b1 15 pM. In tumor-bearing mice, the tumor uptake of [99mTc]Tc-BQ0413 (38 \u00b1 6 %IA/g in PC3-pip 3 h after the injection of 40 pmol) was dependent on PSMA expression (3 \u00b1 2 %IA/g and 0.9 \u00b1 0.3 %IA/g in PSMA-negative PC-3 and SKOV-3 tumors, respectively). We show that both unlabeled BQ0413 and the commonly used binder PSMA-11 enable the blocking of [99mTc]Tc-BQ0413 uptake in normal PSMA-expressing tissues without blocking the uptake in tumors. This resulted in an appreciable increase in tumor-to-organ ratios. At the same injected mass (5 nmol), the use of BQ0413 was more efficient in suppressing renal uptake than the use of PSMA-11. In conclusion, [99mTc]Tc-BQ0413 is a promising probe for the visualization of PSMA-positive lesions using single-photon emission computed tomography (SPECT).", "doi": "10.3390/ijms242417391", "pmid": "38139219", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC10743726"}, {"db": "pii", "key": "ijms242417391"}], "notes": [], "created": "2026-08-21T13:03:48.635Z", "modified": "2026-08-21T13:03:48.835Z"}]}