{"entity": "publication", "iuid": "f774521b0ebe4bbe9166033c111d227f", "timestamp": "2026-08-11T08:16:15.952Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/f774521b0ebe4bbe9166033c111d227f.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/f774521b0ebe4bbe9166033c111d227f"}}, "title": "The effect of macrocyclic chelators on the targeting properties of the 68Ga-labeled gastrin releasing peptide receptor antagonist PEG2-RM26.", "authors": [{"family": "Varasteh", "given": "Zohreh", "initials": "Z"}, {"family": "Mitran", "given": "Bogdan", "initials": "B"}, {"family": "Rosenstr\u00f6m", "given": "Ulrika", "initials": "U"}, {"family": "Velikyan", "given": "Irina", "initials": "I"}, {"family": "Rosestedt", "given": "Maria", "initials": "M"}, {"family": "Lindeberg", "given": "Gunnar", "initials": "G"}, {"family": "S\u00f6rensen", "given": "Jens", "initials": "J"}, {"family": "Larhed", "given": "Mats", "initials": "M"}, {"family": "Tolmachev", "given": "Vladimir", "initials": "V"}, {"family": "Orlova", "given": "Anna", "initials": "A"}], "type": "journal article", "published": "2015-05-00", "journal": {"title": "Nucl. Med. Biol.", "issn": "1872-9614", "volume": "42", "issue": "5", "pages": "446-454", "issn-l": "0969-8051"}, "abstract": "Overexpression of gastrin-releasing peptide receptors (GRPR) has been reported in several cancers. Bombesin (BN) analogs are short peptides with a high affinity for GRPR. Different BN analogs were evaluated for radionuclide imaging and therapy of GRPR-expressing tumors. We have previously investigated an antagonistic analog of BN (D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH(2), RM26) conjugated to NOTA via a PEG(2) spacer (NOTA-PEG(2)-RM26) labeled with (68)Ga, (111)In and Al(18)F. (68)Ga-labeled NOTA-PEG(2)-RM26 showed high tumor-to-organ ratios.\n\nThe influence of different macrocyclic chelators (NOTA, NODAGA, DOTA and DOTAGA) on the targeting properties of (68)Ga-labeled PEG(2)-RM26 was studied in vitro and in vivo.\n\nAll conjugates were labeled with generator-produced (68)Ga with high yields and demonstrated high stability and specific binding to GRPR. The IC(50) values of (nat)Ga-X-PEG(2)-RM26 (X = NOTA, DOTA, NODAGA, DOTAGA) were 2.3 \u00b1 0.2, 3.0 \u00b1 0.3, 2.9 \u00b1 0.3 and 10.0 \u00b1 0.6 nM, respectively. The internalization of the conjugates by PC-3 cells was low. However, the DOTA-conjugated analog demonstrated a higher internalization rate compared to other analogs. GRPR-specific uptake was found in receptor-positive normal tissues and PC-3 xenografts for all conjugates. The biodistribution of the conjugates was influenced by the choice of the chelator moiety. Although all radiotracers cleared rapidly from the blood, [(68)Ga]Ga-NOTA-PEG(2)-RM26 showed significantly lower uptake in lung, muscle and bone compared to the other analogs. The uptake in tumors (5.40 \u00b1 1.04 %ID/g at 2 h p.i.) and the tumor-to-organ ratios (25 \u00b1 3, 157 \u00b1 23 and 39 \u00b1 4 for blood, muscle and bone, respectively) were significantly higher for the NOTA-conjugate than the other analogs.\n\nChelators had a clear influence on the biodistribution and targeting properties of (68)Ga-labeled antagonistic BN analogs. Positively charged [(68)Ga]Ga-NOTA-PEG(2)-RM26 provided a low kidney radioactivity uptake, high affinity, high tumor uptake and high image contrast.", "doi": "10.1016/j.nucmedbio.2014.12.009", "pmid": "25684649", "labels": {"Affiliated researcher": null}, "xrefs": [{"db": "pii", "key": "S0969-8051(14)00574-5"}], "notes": [], "created": "2018-12-05T09:45:41.598Z", "modified": "2018-12-05T09:45:41.635Z"}