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Biodistribution and dosimetry of (177)Lu-tetulomab, a new radioimmunoconjugate for treatment of non-Hodgkin lymphoma.

Abstract
The biodistribution of the anti-CD37 radioimmunoconjugate (177)Lu-tetraxetan-tetulomab ((177)Lu-DOTA-HH1) was evaluated. Biodistribution of (177)Lu-tetraxetan-tetulomab was compared with (177)Lu-tetraxetan-rituximab and free (177)Lu in nude mice implanted with Daudi lymphoma xenografts. The data showed that (177)Lu-tetulomab had a relevant stability and tumor targeting properties in the human lymphoma model. The half-life of (177)Lu allowed significant tumor to normal tissue ratios to be obtained indicating that (177)Lu-tetraxetan-tetulomab could be suitable for clinical testing. The biological and effective half-life in blood was higher for (177)Lu-tetraxetan-tetulomab than for (177)Lu-tetraxetan-rituximab. The biodistribution of (177)Lu-tetraxetan-tetulomab did not change significantly when the protein dose was varied from 0.01 to 1 mg/kg. Dosimetry calculations showed that the absorbed radiation doses to normal tissues and tumor in mice were not significantly different for (177)Lu-tetraxetan-tetuloma b and (177)Lu-tetraxetan-rituximab. The absorbed radiation doses were extrapolated to human absorbed radiation doses. These extrapolated absorbed radiation doses to normal tissues for (177)Lu-tetraxetan-tetulomab at an injection of 40 MBq/kg were significantly lower than the absorbed radiation doses for 15 MBq/kg Zevalin, suggesting that higher tumor radiation dose can be reached with (177)Lu-tetraxetan-tetulomab in the clinic.
AuthorsAda H V Repetto-Llamazares, Roy H Larsen, Camilla Mollatt, Michael Lassmann, Jostein Dahle
JournalCurrent radiopharmaceuticals (Curr Radiopharm) Vol. 6 Issue 1 Pg. 20-7 (Mar 2013) ISSN: 1874-4729 [Electronic] United Arab Emirates
PMID23256748 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Radioisotopes
  • Lutetium
Topics
  • Animals
  • Case-Control Studies
  • Female
  • Humans
  • Lutetium (metabolism, pharmacokinetics)
  • Lymphoma, Non-Hodgkin (metabolism)
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasms, Experimental (metabolism)
  • Radiation Dosage
  • Radioisotopes (metabolism, pharmacokinetics)
  • Tissue Distribution

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