title: Biological evaluation of (177)Lu-labeled DOTA-Ala(SO3H)-Aminooctanoyl-Gln-Trp-Ala-Val-N methyl Gly-His-Statine-Leu-NH2 for gastrin-releasing peptide receptor-positive prostate tumor targeting.
abstract: Bombesin binds with selectivity and high affinity to a Gastrin-releasing peptide receptor (GRPR), which is highly overexpressed in prostate cancer cells. The present study describes the in vitro and in vivo biological characteristics of DOTA-Ala(SO3H)-Aminooctanoyl-Gln-Trp-Ala-Val-N methyl Gly-His-Statine-Leu-NH2 (DOTA-sBBNA), an antagonist analogue of bombesin peptide for the targeting of GRPR. DOTA-sBBNA was synthesized and labeled with (177)Lu as previously published. A saturation assay on PC-3 human prostate cancer cells revealed that the Kd value of the radiolabeled peptide was 1.88 nM with a maximum binding capacity (Bmax) of 289.3 fmol/10(6) cells. The radio-peptide slowly internalized, and 24.4±0.5% of the total binding was internalized in 4hr. Biodistribution studies were conducted in healthy and PC-3 xenografted balb/c mice, which showed high uptake and retention of tumor-associated radioactivity in PC-3 xenografted mice. The tumor-to-blood ratio was 126.02±9.36 at 1.5hr p.i., and was increased to 216.33±61.58 at 24hr p.i., which means that the radiolabeled peptide was highly accumulated in a tumor and rapidly cleared from the blood pool. The GRPR is also over-expressed in Korean prostate cancer patients. These results suggest that this (177)Lu-labeled peptide has promising characteristics for application in nuclear medicine, namely for the diagnosis and treatment of GRPR over-expressing prostate tumors.
authors.affiliation: Radioisotope Research Division, Department of Research Reactor Utilization, Korea Atomic Energy Research Institute, Daejeon 305-353, Republic of Korea; Bio-therapy Human Resources Center, Department of Veterinary Physiology, College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Republic of Korea. Electronic address: limjc@kaeri.re.kr.
authors.forename: Jae Cheong
authors.initials: JC
authors.lastname: Lim
authors.affiliation: Radioisotope Research Division, Department of Research Reactor Utilization, Korea Atomic Energy Research Institute, Daejeon 305-353, Republic of Korea.
authors.forename: Eun Ha
authors.initials: EH
authors.lastname: Cho
authors.affiliation: Radioisotope Research Division, Department of Research Reactor Utilization, Korea Atomic Energy Research Institute, Daejeon 305-353, Republic of Korea.
authors.forename: Jin Joo
authors.initials: JJ
authors.lastname: Kim
authors.affiliation: Radioisotope Research Division, Department of Research Reactor Utilization, Korea Atomic Energy Research Institute, Daejeon 305-353, Republic of Korea.
authors.forename: Sang Mu
authors.initials: SM
authors.lastname: Choi
authors.affiliation: Radioisotope Research Division, Department of Research Reactor Utilization, Korea Atomic Energy Research Institute, Daejeon 305-353, Republic of Korea.
authors.forename: So young
authors.initials: Sy
authors.lastname: Lee
authors.affiliation: Radioisotope Research Division, Department of Research Reactor Utilization, Korea Atomic Energy Research Institute, Daejeon 305-353, Republic of Korea.
authors.forename: Sung Soo
authors.initials: SS
authors.lastname: Nam
authors.affiliation: Radioisotope Research Division, Department of Research Reactor Utilization, Korea Atomic Energy Research Institute, Daejeon 305-353, Republic of Korea.
authors.forename: Ul Jae
authors.initials: UJ
authors.lastname: Park
authors.affiliation: Bio-therapy Human Resources Center, Department of Veterinary Physiology, College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Republic of Korea. Electronic address: parksh@chonnam.ac.kr.
authors.forename: Soo Hyun
authors.initials: SH
authors.lastname: Park
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D000818:Animals; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008187:Lutetium / Q000737:chemistry* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D009842:Oligopeptides / Q000378:metabolism* / Q000493:pharmacokinetics / Q000627:therapeutic use; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy; D011868:Radioisotopes / Q000737:chemistry* / Q000627:therapeutic use; D018004:Receptors, Bombesin / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D000596:Amino Acids; D009842:Oligopeptides; D011868:Radioisotopes; D018004:Receptors, Bombesin; D008187:Lutetium; C013165:statine
keywords: Bombesin; Gastrin releasing peptide receptor; Lutetium-177 ((177)Lu); Tumor targeting