Preclinical comparison in AR4-2J tumor-bearing mice of four radiolabeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-somatostatin analogs for tumor diagnosis and internal radiotherapy

Endocrinology. 2000 Sep;141(9):3304-12. doi: 10.1210/endo.141.9.7683.


Somatostatin analogs labeled with radionuclides are of considerable interest in nuclear oncology as diagnostic or therapeutic tools for somatostatin receptor (SSTR)-expressing tumors. We investigated the suitability of DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) as a replacement for the widely used diethylenetriaminepentaacetic acid, to enable stable labeling of somatostatin analogs with both therapeutic (90Y) and diagnostic (111In) radionuclides. The three clinically relevant somatostatin agonists, octreotide, vapreotide, and lanreotide, together with the newly designed Tyr3-octreotide (TyrOc), were conjugated to DOTA and labeled with 90Y or 111In. For all DOTA-somatostatin analogs tested, irrespective of the incorporated radionuclide, we observed favorable biodistribution profiles in AR4-2J tumor-bearing mice: 1) a rapid clearance from all SSTR-negative tissues except kidney; 2) a specific uptake in SSTR-positive tissues, including tumor; and 3) an excellent tumor penetration. The main route of excretion was via the kidneys. Nevertheless, DOTATOC was clearly superior to the other DOTA-somatostatin analogs tested, as well as OctreoScan, as indicated by the highest tumor-to-nontarget-tissue ratio, including the tumor-to-SSTR-positive-tissue ratios. The presence of different SSTR subtypes in the SSTR-positive tissues possibly contributes to these differential uptakes. We assume that the very favorable behavior of DOTATOC in our mouse model makes this radioligand very promising for future applications in nuclear oncology.

Publication types

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

MeSH terms

  • Animals
  • Chelating Agents / pharmacology
  • Chromatography, High Pressure Liquid
  • Female
  • Heterocyclic Compounds, 1-Ring / chemistry
  • Heterocyclic Compounds, 1-Ring / pharmacokinetics
  • Heterocyclic Compounds, 1-Ring / pharmacology*
  • Hormone Antagonists / pharmacokinetics
  • Hormone Antagonists / pharmacology*
  • Indium Radioisotopes / therapeutic use
  • Kidney / metabolism
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Neoplasms, Experimental / diagnosis*
  • Neoplasms, Experimental / radiotherapy*
  • RNA, Messenger / biosynthesis
  • Radiopharmaceuticals / therapeutic use*
  • Receptors, Somatostatin / drug effects
  • Somatostatin / analogs & derivatives
  • Somatostatin / chemistry
  • Somatostatin / pharmacology*
  • Tissue Distribution
  • Yttrium Radioisotopes / therapeutic use


  • Chelating Agents
  • Heterocyclic Compounds, 1-Ring
  • Hormone Antagonists
  • Indium Radioisotopes
  • RNA, Messenger
  • Radiopharmaceuticals
  • Receptors, Somatostatin
  • Yttrium Radioisotopes
  • 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid
  • Somatostatin