In vitro and in vivo evaluation of 64Cu-TETA-Tyr3-octreotate. A new somatostatin analog with improved target tissue uptake

Nucl Med Biol. 1999 Apr;26(3):267-73. doi: 10.1016/s0969-8051(98)00105-x.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bone and Bones / metabolism
  • Copper Radioisotopes*
  • Female
  • Male
  • Mice
  • Mice, SCID
  • Organometallic Compounds / chemical synthesis
  • Organometallic Compounds / metabolism
  • Organometallic Compounds / pharmacokinetics*
  • Pancreatic Neoplasms / diagnostic imaging
  • Pancreatic Neoplasms / metabolism
  • Papio
  • Radiopharmaceuticals / chemical synthesis*
  • Radiopharmaceuticals / metabolism
  • Radiopharmaceuticals / pharmacokinetics*
  • Rats
  • Rats, Inbred Lew
  • Receptors, Somatostatin / metabolism
  • Somatostatin / analogs & derivatives*
  • Tissue Distribution
  • Tomography, Emission-Computed

Substances

  • Copper Radioisotopes
  • Organometallic Compounds
  • Radiopharmaceuticals
  • Receptors, Somatostatin
  • copper 1,4,8,11-tetraazacyclotetradecane-N,N',N'',N'''-tetraacetic acid tyrosyl(3)-octreotate
  • Somatostatin