Radiation therapy of small cell lung cancer with 177Lu-DOTA-Tyr3-octreotate in an animal model

J Nucl Med. 2004 Sep;45(9):1542-8.

Abstract

Small cell lung cancer (SCLC) is a tumor of neuroendocrine (NE) origin with very low survival rate. Somatostatin receptor scintigraphy using 111In-DTPA-octreotide (DTPA is diethylenetriaminepentaacetic acid) is a well-established method for the visualization of somatostatin receptor-expressing NE tumors. Recently, new combinations of radionuclides and somatostatin analogs have been investigated for therapeutic purposes. In this study, the somatostatin analog DOTA-Tyr3-octreotate (DOTA is 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid), labeled with the medium-energy electron emitter 177Lu (maximal electron energy = 498 keV, half-life = 6.6 d), was used for radiation therapy of human SCLC in an animal model.

Methods: Nude mice, bearing tumors from the human SCLC cell line NCI-H69, were injected intravenously with 177Lu-DOTA-Tyr3-octreotate. Groups of animals (n = 5 or 6) were injected with 45-, 60-, and 120-MBq fractions and two 45-MBq fractions 48 h apart. Furthermore, 1 control group was treated with unlabeled DOTA-Tyr3-octreotate and another control group was not treated.

Results: In both control groups, the tumor volumes were increased 2-fold in approximately 5 d. Treatment with 177Lu-DOTA-Tyr3-octreotate resulted in marked tumor regression with statistically significant tumor volume reduction after 1 wk (P < 0.001). The tumor growth delay time was dependent on the amount of injected activity for the groups with single injections, 26 d for 60 MBq and 40 d for 120 MBq. The best therapeutic effect was obtained in mice injected with 2 fractions of 45 MBq. The relative tumor volume after 1 mo was 0.004 +/- 0.004.

Conclusion: Radiation therapy with 177Lu-DOTA-Tyr3-octreotate on SCLC-bearing mice was successful. Since the experiments were performed on a human SCLC cell line xenografted to nude mice, the results may be clinically relevant and treatment with 177Lu-DOTA-Tyr3-octreotate could be a treatment alternative in this tumor disease that normally has a dismal prognosis.

Publication types

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

MeSH terms

  • Animals
  • Carcinoma, Small Cell / metabolism*
  • Carcinoma, Small Cell / radiotherapy*
  • Disease Models, Animal
  • Injections, Intravenous
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / radiotherapy
  • Male
  • Metabolic Clearance Rate
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Octreotide / analogs & derivatives
  • Organ Specificity
  • Organometallic Compounds / administration & dosage
  • Organometallic Compounds / pharmacokinetics*
  • Organometallic Compounds / therapeutic use*
  • Radiopharmaceuticals / administration & dosage
  • Radiopharmaceuticals / pharmacokinetics
  • Radiopharmaceuticals / therapeutic use
  • Tissue Distribution
  • Treatment Outcome

Substances

  • Organometallic Compounds
  • Radiopharmaceuticals
  • lutetium Lu 177 dotatate
  • Octreotide