Dosimetric analysis of 177Lu-DOTA-rituximab in patients with relapsed/refractory non-Hodgkin's lymphoma

Nucl Med Commun. 2016 Jul;37(7):735-42. doi: 10.1097/MNM.0000000000000501.

Abstract

Objective: Radioimmunotherapy targeting CD20 receptors in lymphoma using radiolabeled chimeric antibodies may lead to better therapeutic responses than cold anti-CD20 antibodies. This study aimed to assess the biodistribution and present reasonable estimates of normal organ doses, including red marrow using Lu-DOTA-rituximab.

Materials and methods: Patients with relapsed/refractory CD20+ B-cell non-Hodgkin's lymphoma were recruited into this prospective study. In-house labeling of Lu-DOTA-rituximab was performed and administered after quality assurance. Rituximab (375 mg/m), followed by 50 mCi (1850 MBq) of Lu-DOTA-rituximab was administered as a slow intravenous infusion and emission images were acquired. Regions of interest were drawn for kidney, liver, heart, bladder, spleen, and tumor lesions on both anterior and posterior images. Internal dose estimation was performed using OLINDA v1.0 software.

Results: The mean age of the 10 patients (eight men and two women) was 52±13 years. The uptake of radiolabeled antibody was visualized within 30 min of administration in the liver, kidneys, heart, spleen, and bladder. The coefficient of determination (R) was greater than 0.95 for organs and the whole body in all patients. The effective half-life of radioimmunoconjugate was 100±28 h (42-126 h). The critical organ in our study was the red marrow. The average total body dose, effective dose, and effective dose equivalent calculated in all 10 patients were 0.13±0.02, 0.15±0.03, and 0.22±0.04 mGy/MBq, respectively.

Conclusion: There may be considerable interindividual differences in absorbed doses of organs and generalization or extrapolation of doses in the clinical setting at present is not feasible with Lu-DOTA-rituximab in non-Hodgkin's lymphoma patients. Patient-specific dosimetry is thus recommended to eliminate the variations and reduce the possibility of dose-limiting toxicity.

Publication types

  • Clinical Trial

MeSH terms

  • Antibodies, Monoclonal, Murine-Derived / analysis
  • Antibodies, Monoclonal, Murine-Derived / therapeutic use*
  • Female
  • Humans
  • Lymphoma, Non-Hodgkin / radiotherapy*
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / prevention & control*
  • Organometallic Compounds / analysis
  • Organometallic Compounds / therapeutic use*
  • Radiation Exposure / analysis*
  • Radioimmunotherapy / methods*
  • Radiopharmaceuticals / analysis
  • Radiopharmaceuticals / therapeutic use
  • Radiotherapy Dosage
  • Recurrence
  • Rituximab
  • Treatment Outcome
  • Whole-Body Counting*

Substances

  • 177Lu-DOTA-rituximab
  • Antibodies, Monoclonal, Murine-Derived
  • Organometallic Compounds
  • Radiopharmaceuticals
  • Rituximab