Differences in biodistribution between 99mTc-depreotide, 111In-DTPA-octreotide, and 177Lu-DOTA-Tyr3-octreotate in a small cell lung cancer animal model

Cancer Biother Radiopharm. 2005 Apr;20(2):231-6. doi: 10.1089/cbr.2005.20.231.

Abstract

Aim: (177)Lu-DOTA-Tyr(3)-octreotate is a candidate radiopharmaceutical for the therapy of somatostatin receptor (sstr)-positive small cell lung cancer (SCLC). Scintigraphy of lung tumors is made with 2 alternative somatostatin analogs, (111)In-DTPA-octreotide or (99m)Tc-depreotide. The aim of this study was to compare the biodistribution of these 3 radiopharmaceuticals in SCLC xenografted to nude mice.

Methods: Nude mice, bearing tumors from the human SCLC cell line NCI-H69, were intravenously injected with 10 MBq (2.4 microg) (99m)Tc-depreotide and 2 MBq (0.5 microg) (111)In-DTPA-octreotide simultaneously. The activity concentration (%IA/g) was measured in tumor and normal tissue at 2, 4, and 24 hours postinjection (hpi). The results were compared with earlier published biodistribution data of 3 MBq (0.7 microg) (177)Lu-DOTA-Tyr(3)-octreotate in the same animal model.

Results: The activity concentration of (111)In-DTPAoctreotide in tumor was higher than the activity concentration of (99m)Tc-depreotide at 2-24 hpi, p < 0.05. The highest tumor uptake at 24 hpi was, however, found for (177)Lu-DOTA-Tyr(3)-octreotate. The activity concentration of (99m)Tc-depreotide was significantly higher in the heart, lungs, liver, the salivary glands, spleen, and bone marrow than for (111)In-DTPA-octreotide at 2-24 hpi. Saturation of the somatostatin receptors may have influenced the uptake in tumor and sstr-positive normal tissues.

Conclusion: The low tumor-to-lung and tumor-to-liver activity concentration ratios for (99m)Tc-depreotide could result in a lower detection rate of SCLC with this compound versus (111)In-DTPA-octreotide. (177)Lu-DOTA-Tyr(3)-octreotate gave the highest tumor-activity concentration, and has, thus, the best properties for therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Small Cell / radiotherapy*
  • Cell Line, Tumor
  • Disease Models, Animal
  • Humans
  • Indium Radioisotopes / pharmacokinetics
  • Liver / pathology
  • Lung / pathology
  • Lung Neoplasms / radiotherapy*
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Neoplasms, Experimental / therapy
  • Octreotide / analogs & derivatives*
  • Octreotide / pharmacokinetics*
  • Organometallic Compounds / pharmacokinetics*
  • Organotechnetium Compounds / pharmacokinetics*
  • Pentetic Acid / analogs & derivatives*
  • Pentetic Acid / pharmacokinetics*
  • Radiopharmaceuticals
  • Somatostatin / analogs & derivatives*
  • Somatostatin / pharmacokinetics*
  • Time Factors
  • Tissue Distribution

Substances

  • 111In-octreotide, DTPA(0)-
  • Indium Radioisotopes
  • Organometallic Compounds
  • Organotechnetium Compounds
  • Radiopharmaceuticals
  • Somatostatin
  • Pentetic Acid
  • technetium Tc 99m depreotide
  • lutetium Lu 177 dotatate
  • Octreotide