title: Evaluation of a ⁶⁴Cu‑labeled 1,4,7‑triazacyclononane, 1‑glutaric acid‑4,7 acetic acid (NODAGA)‑galactose‑bombesin analogue as a PET imaging probe in a gastrin‑releasing peptide receptor‑expressing prostate cancer xenograft model.
abstract: Gastrin‑releasing peptide receptor (GRPR) is overexpressed by a variety of human tumors and in particular, identiﬁed to be upregulated in prostate cancers. The current study aimed to develop clinically translatable BBN analogue‑based radioligands for positron emission tomography (PET) of GRPR‑positive tumors. We developed radiolabeled BBN analogues and modified radiolabeled galacto‑BBN analogues and then investigated their tumor‑targeting efficacy in vivo. The chelator 1,4,7‑triazacyclononane, 1‑glutaric acid‑4,7 acetic acid (NODAGA) was used to radiolabel the peptides with 64Cu. The peptides were evaluated by measuring cell‑based receptor‑binding affinities. Biodistribution experiments and small animal imaging using PET were performed in nude mice bearing subcutaneous PC3 human prostate cancer xenografts. The conjugates were radiolabeled with yields >99%. The stability assay showed that [64Cu]NODAGA‑BBN and [64Cu]NODAGA‑galacto‑BBN remained stable in both human and mouse serum for 1 h at 37˚C. PET images of PC3 tumor‑bearing nude mice were acquired at 1, 3, 24, 48 and 72 h after injection. [64Cu]NODAGA‑galacto‑BBN showed retention in tumors for 72 h, low liver uptake, and rapid renal clearance. PET imaging results were also confirmed by biodistrubution 1 and 3 h after injection. [64Cu]NODAGA‑BBN and [64Cu]NODAGA‑galacto‑BBN are promising new PET probes for GRPR‑positive prostate cancer.
authors.affiliation: Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences (KIRAMS), Seoul, Republic of Korea.
authors.forename: Min Hwan
authors.initials: MH
authors.lastname: Kim
authors.affiliation: Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences (KIRAMS), Seoul, Republic of Korea.
authors.forename: Ji Ae
authors.initials: JA
authors.lastname: Park
authors.affiliation: Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences (KIRAMS), Seoul, Republic of Korea.
authors.forename: Sang-Keun
authors.initials: SK
authors.lastname: Woo
authors.affiliation: Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences (KIRAMS), Seoul, Republic of Korea.
authors.forename: Kyo Chul
authors.initials: KC
authors.lastname: Lee
authors.affiliation: Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences (KIRAMS), Seoul, Republic of Korea.
authors.forename: Gwang Il
authors.initials: GI
authors.lastname: An
authors.affiliation: Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences (KIRAMS), Seoul, Republic of Korea.
authors.forename: Byoung Soo
authors.initials: BS
authors.lastname: Kim
authors.affiliation: Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences (KIRAMS), Seoul, Republic of Korea.
authors.forename: Kwang Il
authors.initials: KI
authors.lastname: Kim
authors.affiliation: Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences (KIRAMS), Seoul, Republic of Korea.
authors.forename: Tae Sup
authors.initials: TS
authors.lastname: Lee
authors.affiliation: School of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.
authors.forename: Chan Wha
authors.initials: CW
authors.lastname: Kim
authors.affiliation: Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences (KIRAMS), Seoul, Republic of Korea.
authors.forename: Kyeong Min
authors.initials: KM
authors.lastname: Kim
authors.affiliation: Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences (KIRAMS), Seoul, Republic of Korea.
authors.forename: Joo Hyun
authors.initials: JH
authors.lastname: Kang
authors.affiliation: Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences (KIRAMS), Seoul, Republic of Korea.
authors.forename: Yong Jin
authors.initials: YJ
authors.lastname: Lee
mesh_terms: D000085:Acetates / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D001839:Bombesin / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D003301:Copper Radioisotopes / Q000493:pharmacokinetics; D005260:Female; D005690:Galactose / Q000737:chemistry / Q000493:pharmacokinetics; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry / Q000493:pharmacokinetics; D064593:Heterografts; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D049268:Positron-Emission Tomography / Q000379:methods*; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018004:Receptors, Bombesin / Q000235:genetics*
chemical_list: C572723:1-(1,3-carboxypropyl)-4,7-carboxymethyl-1,4,7-triazacyclononane; D000085:Acetates; D003301:Copper Radioisotopes; D006573:Heterocyclic Compounds, 1-Ring; D018004:Receptors, Bombesin; D001839:Bombesin; D005690:Galactose