Novel targeted nuclear imaging agent for gastric cancer diagnosis: Glucose-regulated protein 78 binding peptide-guided ¹¹¹In-labeled polymeric micelles

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(ε-caprolactone) and then mixed with diethylenetriaminepentaacetic acid (DTPA)-linked poly(ethylene glycol)-poly(ε-caprolactone) to form DTPA/GRP78BP-conjugated micelles. The coupling efficiency of micelles with radioisotope indium-¹¹¹ (¹¹¹In) was measured and analyzed by instant thin layer chromatography. The coupling efficiency of DTPA-conjugated micelles and DTPA/GRP78BP-conjugated micelles with ¹¹¹In was 85% and 93%, respectively. For characterization and trace imaging, the radioisotope ¹¹¹In-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 ¹¹¹In-labeled micelles was statistically higher than that in animals administered with ¹¹¹In-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.