title: Synthesis, radiolabeling, and preclinical evaluation of a new octreotide analog for somatostatin receptor-positive tumor scintigraphy.
abstract: Radiolabeled somatostatin analogs have become powerful tools in the diagnosis and staging of neuroendocrine tumors, which express somatostatin receptors. The aim of this study was to evaluate a new somatostatin analog, 6-hydrazinopyridine-3-carboxylic acid-Ser3-octreotate (HYNIC-SATE) radiolabeled with 99mTc, using ethylenediamine-N,N'-diacetic acid and tricine as coligands, to be used as a radiopharmaceutical for the in vivo imaging of somatostatin receptor subtype 2 (SSTR2)-positive tumor. Synthesis of the peptide was carried out on a solid phase using a standard Fmoc strategy. Peptide conjugate affinities for SSTR2 were determined by receptor binding affinity on rat brain cortex and C6 cell membranes. Internalization rate of 99mTc-HYNIC-SATE was studied in SSTR2-expressing C6 cells that were used for intracranial tumor studies in rat brain. A reproducible in vivo C6 glioma model was developed in Sprague-Dawley rat and confirmed by histopathology and immunohistochemical analysis. Biodistribution and imaging properties of this new radiopeptide were also studied in C6 tumor-bearing rats. Radiolabeling was performed at high specific activities, with a radiochemical purity of >96%. Peptide conjugate showed high affinity binding for SSTR2 (HYNIC-SATE IC50=1.60±0.05 n m) and specific internalization into rat C6 cells. After administration of 99mTc-HYNIC-SATE in C6 glioma-bearing rats, a receptor specific uptake of radioactivity was observed in SSTR-positive organs and in the implanted intracranial tumor and rapid excretion from nontarget tissues via kidneys. 99mTc-HYNIC-SATE is a new receptor-specific radiopeptide for targeting SSTR2-positive brain tumor and might be of great promise in the scintigraphy of SSTR2-positive tumors.
authors.affiliation: Department of Infectious Diseases and Immunology (Nuclear Medicine Division), Council of Scientific and Industrial Research (CSIR) - Indian Institute of Chemical Biology (IICB), 4 Raja S C Mullick Road, Kolkata, 700032, West Bengal, India.
authors.forename: Kakali
authors.initials: K
authors.lastname: De
authors.forename: Arijit
authors.initials: A
authors.lastname: Bhowmik
authors.forename: Ashok
authors.initials: A
authors.lastname: Behera
authors.forename: Indranil
authors.initials: I
authors.lastname: Banerjee
authors.forename: Mrinal Kanti
authors.initials: MK
authors.lastname: Ghosh
authors.forename: Mridula
authors.initials: M
authors.lastname: Misra
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D005910:Glioma / Q000000981:diagnostic imaging* / Q000378:metabolism; D009368:Neoplasm Transplantation; D015282:Octreotide / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000493:pharmacokinetics; D015609:Organotechnetium Compounds / Q000138:chemical synthesis / Q000378:metabolism / Q000493:pharmacokinetics; D011485:Protein Binding; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000378:metabolism / Q000493:pharmacokinetics; D017207:Rats, Sprague-Dawley; D017481:Receptors, Somatostatin / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D017481:Receptors, Somatostatin; C115977:Sstr2 protein, rat; C000599291:technetium 99m 6-hydrazinopyridine-3-carboxylic acid-Ser3-octreotate; D015282:Octreotide
keywords: 99mTc; C6 glioma; HYNIC; octreotide; somatostatin receptor