{"entity": "researcher", "timestamp": "2026-08-20T21:02:55.838Z", "family": "Tolmachev", "given": "Vladimir", "initials": "V", "orcid": "0000-0002-6122-1734", "affiliations": ["Department of Immunology, Genetics and Pathology, Uppsala University, 751 23 Uppsala, Sweden. vladimir.tolmachev@igp.uu.se."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/896ae9fae8b74251afe11b4354c62794.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/896ae9fae8b74251afe11b4354c62794"}}, "publications": [{"entity": "publication", "iuid": "cfb53aa09f7b4a359bf70b8e34652e7f", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/cfb53aa09f7b4a359bf70b8e34652e7f.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/cfb53aa09f7b4a359bf70b8e34652e7f"}}, "title": "The GRPR Antagonist [99mTc]Tc-maSSS-PEG2-RM26 towards Phase I Clinical Trial: Kit Preparation, Characterization and Toxicity.", "authors": [{"family": "Abouzayed", "given": "Ayman", "initials": "A"}, {"family": "Borin", "given": "Jesper", "initials": "J"}, {"family": "Lundmark", "given": "Fanny", "initials": "F", "orcid": "0000-0002-9153-2832", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c6690e6a499c48e98f5c7f6038bb463c.json"}}, {"family": "Rybina", "given": "Anastasiya", "initials": "A"}, {"family": "Hober", "given": "Sophia", "initials": "S", "orcid": "0000-0003-0605-8417", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4a1bdfd8500c4dbea343132bc0d8e44c.json"}}, {"family": "Zelchan", "given": "Roman", "initials": "R"}, {"family": "Tolmachev", "given": "Vladimir", "initials": "V", "orcid": "0000-0002-6122-1734", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/896ae9fae8b74251afe11b4354c62794.json"}}, {"family": "Chernov", "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": "2023-05-02", "journal": {"title": "Diagnostics (Basel)", "issn": "2075-4418", "volume": "13", "issue": "9", "issn-l": null}, "abstract": "Gastrin-releasing peptide receptors (GRPRs) are overexpressed in the majority of primary prostate tumors and in prostatic lymph node and bone metastases. Several GRPR antagonists were developed for SPECT and PET imaging of prostate cancer. We previously reported a preclinical evaluation of the GRPR antagonist [99mTc]Tc-maSSS-PEG2-RM26 (based on [D-Phe6, Sta13, Leu14-NH2]BBN(6-14)) which bound to GRPR with high affinity and had a favorable biodistribution profile in tumor-bearing animal models. In this study, we aimed to prepare and test kits for prospective use in an early-phase clinical study. The kits were prepared to allow for a one-pot single-step radiolabeling with technetium-99m pertechnetate. The kit vials were tested for sterility and labeling efficacy. The radiolabeled by using the kit GRPR antagonist was evaluated in vitro for binding specificity to GRPR on PC-3 cells (GRPR-positive). In vivo, the toxicity of the kit constituents was evaluated in rats. The labeling efficacy of the kits stored at 4 \u00b0C was monitored for 18 months. The biological properties of [99mTc]Tc-maSSS-PEG2-RM26, which were obtained after this period, were examined both in vitro and in vivo. The one-pot (gluconic acid, ethylenediaminetetraacetic acid, stannous chloride, and maSSS-PEG2-RM26) single-step radiolabeling with technetium-99m was successful with high radiochemical yields (>97%) and high molar activities (16-24 MBq/nmol). The radiolabeled peptide maintained its binding properties to GRPR. The kit constituents were sterile and non-toxic when tested in living subjects. In conclusion, the prepared kit is considered safe in animal models and can be further evaluated for use in clinics.", "doi": "10.3390/diagnostics13091611", "pmid": "37175001", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC10178091"}, {"db": "pii", "key": "diagnostics13091611"}], "notes": [], "created": "2026-08-20T13:40:30.341Z", "modified": "2026-08-20T13:40:30.454Z"}, {"entity": "publication", "iuid": "53a49c26113a49c7b81046171f734e46", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/53a49c26113a49c7b81046171f734e46.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/53a49c26113a49c7b81046171f734e46"}}, "title": "Heterodimeric Radiotracer Targeting PSMA and GRPR for Imaging of Prostate Cancer-Optimization of the Affinity towards PSMA by Linker Modification in Murine Model.", "authors": [{"family": "Lundmark", "given": "Fanny", "initials": "F", "orcid": "0000-0002-9153-2832", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c6690e6a499c48e98f5c7f6038bb463c.json"}}, {"family": "Abouzayed", "given": "Ayman", "initials": "A"}, {"family": "Mitran", "given": "Bogdan", "initials": "B"}, {"family": "Rinne", "given": "Sara S", "initials": "SS"}, {"family": "Varasteh", "given": "Zohreh", "initials": "Z"}, {"family": "Larhed", "given": "Mats", "initials": "M", "orcid": "0000-0001-6258-0635", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/225695195abc4233bd141e6858e72e7f.json"}}, {"family": "Tolmachev", "given": "Vladimir", "initials": "V", "orcid": "0000-0002-6122-1734", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/896ae9fae8b74251afe11b4354c62794.json"}}, {"family": "Rosenstr\u00f6m", "given": "Ulrika", "initials": "U", "orcid": "0000-0002-0817-8140", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ec6820fcb786475d85969630b0b3860b.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": "2020-07-01", "journal": {"title": "Pharmaceutics", "issn": "1999-4923", "volume": "12", "issue": "7", "issn-l": null}, "abstract": "Prostate-specific membrane antigen (PSMA) and gastrin-releasing peptide receptor (GRPR) are promising targets for molecular imaging of prostate cancer (PCa) lesions. Due to the heterogenic overexpression of PSMA and GRPR in PCa, a heterodimeric radiotracer with the ability to bind to both targets could be beneficial. Recently, our group reported the novel heterodimer BQ7800 consisting of a urea-based PSMA inhibitor, the peptide-based GRPR antagonist RM26 and NOTA chelator. The study reported herein, aimed to improve the affinity of BQ7800 towards PSMA by changing the composition of the two linkers connecting the PSMA- and GRPR-targeting motifs. Three novel heterodimeric analogues were synthesized by incorporation of phenylalanine in the functional linker of the PSMA-binding motif and/or shortening the PEG-linker coupled to RM26. The heterodimers were labeled with indium-111 and evaluated in vitro. In the competitive binding assay, BQ7812, featuring phenylalanine and shorter PEG-linker, demonstrated a nine-fold improved affinity towards PSMA. In the in vivo biodistribution study of [111In]In-BQ7812 in PC3-pip tumor-bearing mice (PSMA and GRPR positive), the activity uptake was two-fold higher in the tumor and three-fold higher in kidneys than for [111In]In-BQ7800. Herein, we showed that the affinity of a bispecific PSMA/GRPR heterodimer towards PSMA could be improved by linker modification.", "doi": "10.3390/pharmaceutics12070614", "pmid": "32630176", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC7408065"}, {"db": "pii", "key": "pharmaceutics12070614"}], "notes": [], "created": "2026-08-20T13:42:59.018Z", "modified": "2026-08-20T13:42:59.116Z"}, {"entity": "publication", "iuid": "f231ab25ca63453aabd43fca29e1bc82", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/f231ab25ca63453aabd43fca29e1bc82.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/f231ab25ca63453aabd43fca29e1bc82"}}, "title": "Bispecific GRPR-Antagonistic Anti-PSMA/GRPR Heterodimer for PET and SPECT Diagnostic Imaging of Prostate Cancer.", "authors": [{"family": "Mitran", "given": "Bogdan", "initials": "B"}, {"family": "Varasteh", "given": "Zohreh", "initials": "Z"}, {"family": "Abouzayed", "given": "Ayman", "initials": "A"}, {"family": "Rinne", "given": "Sara S", "initials": "SS"}, {"family": "Puuvuori", "given": "Emmi", "initials": "E"}, {"family": "De Rosa", "given": "Maria", "initials": "M", "orcid": "0000-0002-4087-2554", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0723571cbae046a3b06daacced710bd9.json"}}, {"family": "Larhed", "given": "Mats", "initials": "M", "orcid": "0000-0001-6258-0635", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/225695195abc4233bd141e6858e72e7f.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"}}, {"family": "Rosenstr\u00f6m", "given": "Ulrika", "initials": "U", "orcid": "0000-0002-0817-8140", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ec6820fcb786475d85969630b0b3860b.json"}}], "type": "journal article", "published": "2019-09-14", "journal": {"title": "Cancers (Basel)", "issn": "2072-6694", "volume": "11", "issue": "9", "issn-l": "2072-6694"}, "abstract": "Simultaneous targeting of the prostate-specific membrane antigen (PSMA) and gastrin-releasing peptide receptor (GRPR) could improve the diagnostic accuracy in prostate cancer (PCa). The aim of this study was to develop a PSMA/GRPR-targeting bispecific heterodimer for SPECT and positron emission tomography (PET) diagnostic imaging of PCa. The heterodimer NOTA-DUPA-RM26 was produced by manual solid-phase peptide synthesis. NOTA-DUPA-RM26 was labeled with 111In and 68Ga, with yields >98%, and demonstrated a high stability and binding specificity to PSMA and GRPR. IC50 values for natIn-NOTA-DUPA-RM26 were 4 \u00b1 1 nM towards GRPR and 824 \u00b1 230 nM towards PSMA. An in vivo binding specificity 1 h pi of 111In-NOTA-DUPA-RM26 in PC3-PIP-xenografted mice demonstrated partially blockable tumor uptake when co-injected with an excess of PSMA- or GRPR-targeting agents. Simultaneous co-injection of both agents induced pronounced blocking. The biodistribution of 111In-NOTA-DUPA-RM26 and 68Ga-NOTA-DUPA-RM26 revealed fast activity clearance from the blood and normal organs via the kidneys. Tumor uptake exceeded normal organ uptake for both analogs 1 h pi. 68Ga-NOTA-DUPA-RM26 had a significantly lower tumor uptake (8 \u00b1 2%ID/g) compared to 111In-NOTA-DUPA-RM26 (12 \u00b1 2%ID/g) 1 h pi. Tumor-to-organ ratios increased 3 h pi, but decreased 24 h pi, for 111In-NOTA-DUPA-RM26. MicroPET/CT and microSPECT/CT scans confirmed biodistribution data, suggesting that 68Ga-NOTA-DUPA-RM26 and 111In-NOTA-DUPA-RM26 are suitable candidates for the imaging of GRPR and PSMA expression in PCa shortly after administration.", "doi": "10.3390/cancers11091371", "pmid": "31540122", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC6771040"}, {"db": "pii", "key": "cancers11091371"}], "notes": [], "created": "2026-08-20T13:39:15.966Z", "modified": "2026-08-20T13:39:16.126Z"}, {"entity": "publication", "iuid": "72a8c3b95b674cf186a9698113f12544", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/72a8c3b95b674cf186a9698113f12544.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/72a8c3b95b674cf186a9698113f12544"}}, "title": "Synthesis and Preclinical Evaluation of Radio-Iodinated GRPR/PSMA Bispecific Heterodimers for the Theranostics Application in Prostate Cancer.", "authors": [{"family": "Abouzayed", "given": "Ayman", "initials": "A"}, {"family": "Yim", "given": "Cheng-Bin", "initials": "CB"}, {"family": "Mitran", "given": "Bogdan", "initials": "B"}, {"family": "Rinne", "given": "Sara S", "initials": "SS"}, {"family": "Tolmachev", "given": "Vladimir", "initials": "V", "orcid": "0000-0002-6122-1734", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/896ae9fae8b74251afe11b4354c62794.json"}}, {"family": "Larhed", "given": "Mats", "initials": "M", "orcid": "0000-0001-6258-0635", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/225695195abc4233bd141e6858e72e7f.json"}}, {"family": "Rosenstr\u00f6m", "given": "Ulrika", "initials": "U"}, {"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": "2019-07-23", "journal": {"title": "Pharmaceutics", "issn": "1999-4923", "volume": "11", "issue": "7", "issn-l": null}, "abstract": "Gastrin-releasing peptide receptor (GRPR) and prostate-specific membrane antigen (PSMA) are overexpressed in most prostate cancers. GRPR expression is higher in early stages while PSMA expression increases with progression. The possibility of targeting both markers with a single theranostics radiotracer could improve patient management. Three GRPR/PSMA-targeting bispecific heterodimers (urea derivative PSMA-617 and bombesin-based antagonist RM26 linked via X-triazolyl-Tyr-PEG2, X = PEG2 (BO530), (CH2)8 (BO535), none (BO536)) were synthesized by solid-phase peptide synthesis. Peptides were radio-iodinated and evaluated in vitro for binding specificity, cellular retention, and affinity. In vivo specificity for all heterodimers was studied in PC-3 (GRPR-positive) and LNCaP (PSMA-positive) xenografts. [125I]I-BO530 was evaluated in PC-3pip (GRPR/PSMA-positive) xenografts. Micro single-photon emission computed tomography/computed tomography (microSPECT/CT) scans were acquired. The heterodimers were radiolabeled with high radiochemical yields, bound specifically to both targets, and demonstrated high degree of activity retention in PC-3pip cells. Only [125I]I-BO530 demonstrated in vivo specificity to both targets. A biodistribution study of [125I]I-BO530 in PC-3pip xenografted mice showed high tumor activity uptake (30%-35%ID/g at 3 h post injection (pi)). Activity uptake in tumors was stable and exceeded all other organs 24 h pi. Activity uptake decreased only two-fold 72 h pi. The GRPR/PSMA-targeting heterodimer [125I]I-BO530 is a promising agent for theranostics application in prostate cancer.", "doi": "10.3390/pharmaceutics11070358", "pmid": "31340483", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC6680768"}, {"db": "pii", "key": "pharmaceutics11070358"}], "notes": [], "created": "2026-08-20T13:42:56.984Z", "modified": "2026-08-20T13:42:57.066Z"}]}