title: Novel targeted nuclear imaging agent for gastric cancer diagnosis: glucose-regulated protein 78 binding peptide-guided 111In-labeled polymeric micelles.
abstract: Increased expression of cellular membrane bound glucose-regulated protein 78 (GRP78) is considered to be one of the biomarkers for gastric cancers. Therefore, peptides or molecules with specific recognition to GRP78 can act as a guiding probe to direct conjugated imaging agents to localized cancers. Based on this rationale, GRP78-guided polymeric micelles were designed and manufactured for nuclear imaging detection of tumors. Thiolated GRP78 binding peptide (GRP78BP) was first labeled with maleimide-terminated poly(ethylene glycol)- poly(ɛ-caprolactone) and then mixed with diethylenetriaminepentaacetic acid (DTPA)-linked poly(ethylene glycol)-poly(ɛ-caprolactone) to form DTPA/GRP78BP-conjugated micelles. The coupling efficiency of micelles with radioisotope indium-111 ((111)In) was measured and analyzed by instant thin layer chromatography. The coupling efficiency of DTPA-conjugated micelles and DTPA/GRP78BP-conjugated micelles with (111)In was 85% and 93%, respectively. For characterization and trace imaging, the radioisotope (111)In-targeting tumors were detected and imaged in a xenograft murine model using nano single photon emission computed tomography/computed tomography. The results revealed that the radioactive intensity measured in the animals administered with GRP78BP-guided (111)In-labeled micelles was statistically higher than that in animals administered with (111)In-labeled micelles, demonstrating that GRP78BP more than doubled the accumulation of micelles to the tumor tissue (P < 0.05). The results indicate that the gastric cancer biomarker GRP78 is a probing target in the application of nuclear imaging for tumor diagnosis. This novel GRP78BP-guided micelle agent may be applied in clinical practice to complement the histological diagnosis.
authors: Graduate Institute of Medical Sciences, Taipei Medical University, Taipei, Taiwan.
authors: Chun-Chia
authors: CC
authors: Cheng
authors: Chiung-Fang
authors: CF
authors: Huang
authors: Ai-Sheng
authors: AS
authors: Ho
authors: Cheng-Liang
authors: CL
authors: Peng
authors: Chun-Chao
authors: CC
authors: Chang
authors: Fu-Der
authors: FD
authors: Mai
authors: Ling-Yun
authors: LY
authors: Chen
authors: Tsai-Yueh
authors: TY
authors: Luo
authors: Jungshan
authors: J
authors: Chang
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins / Q000378:metabolism*; D064593:Heterografts; D006801:Humans; D007205:Indium Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics; D051379:Mice; D008819:Mice, Nude; D008823:Micelles; D057054:Molecular Imaging / Q000379:methods*; D010316:Particle Size; D010455:Peptides / Q000737:chemistry / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000493:pharmacokinetics; D013274:Stomach Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D004337:Drug Carriers; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D007205:Indium Radioisotopes; D008823:Micelles; D010455:Peptides; D019275:Radiopharmaceuticals
keywords: biomarker; gastric cancer; glucose-regulated protein 78; micelles; nuclear imaging
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