title: In vitro and in vivo evaluation of 64Cu-TETA-Tyr3-octreotate. A new somatostatin analog with improved target tissue uptake.
abstract: Radiolabeled somatostatin analogs have demonstrated potential as cancer therapeutic agents. Many of these agents are based on the analog octreotide (OC). Recently it has been shown that substitution of a tyrosine for phenylalanine in the 3-position and changing the C-terminus from an alcohol to an acid improves the targeting of somatostatin-rich tissues. The compound, 1,4,8,11-tetraazacyclotetradecane-N,N',N",N"'-tetraacetic acid-Tyr3-octreotate (TETA-Y3-TATE), was synthesized and radiolabeled with 64Cu. The receptor binding properties of 64Cu-TETA-Y3-TATE showed an estimated Kd value of 549 pM in somatostatin receptor-positive CA20948 tissue membrane. High tumor uptake was observed in two animal tumor models. Tumor uptakes of 2.37 %ID/g in CA20948 tumor-bearing rats and 21.60 %ID/g in AR42J tumor-bearing SCID mice were observed at 1 h, compared with 1.09 %ID/g and 11.24 %ID/g for 64Cu-TETA-OC. Higher uptake in other somatostatin-receptor rich tissues was also observed, compared with 64Cu-TETA-OC. Positron emission tomography (PET) imaging with 64Cu-TETA-Y3-TATE in a baboon showed significant uptake in the pituitary and adrenals, and clearance through the kidneys. 64Cu-TETA-Y3-TATE, a new OC analog for binding somatostatin receptors, demonstrated significantly greater uptake in somatostatin-rich tissues in two tumor-bearing animal models, and demonstrated great potential as a radiopharmaceutical for imaging and therapy of somatostatin receptor-positive tissues.
authors.affiliation: Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: J S
authors.initials: JS
authors.lastname: Lewis
authors.forename: A
authors.initials: A
authors.lastname: Srinivasan
authors.forename: M A
authors.initials: MA
authors.lastname: Schmidt
authors.forename: C J
authors.initials: CJ
authors.lastname: Anderson
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000378:metabolism; D003301:Copper Radioisotopes; D005260:Female; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000378:metabolism / Q000493:pharmacokinetics*; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism; D010215:Papio; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000378:metabolism / Q000493:pharmacokinetics*; D051381:Rats; D011917:Rats, Inbred Lew; D017481:Receptors, Somatostatin / Q000378:metabolism; D013004:Somatostatin / Q000031:analogs & derivatives*; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
chemical_list: D003301:Copper Radioisotopes; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; D017481:Receptors, Somatostatin; C120244:copper 1,4,8,11-tetraazacyclotetradecane-N,N',N'',N'''-tetraacetic acid tyrosyl(3)-octreotate; D013004:Somatostatin