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Biodistribution and Dosimetry of 177Lu-tetulomab, a New Radioimmunoconjugate for Treatment of Non-Hodgkin Lymphoma

[ Vol. 6 , Issue. 1 ]

Author(s):

Ada H. V. Repetto-Llamazares, Roy H. Larsen, Camilla Mollatt, Michael Lassmann and Jostein Dahle   Pages 20 - 27 ( 8 )

Abstract:


The biodistribution of the anti-CD37 radioimmunoconjugate 177Lu-tetraxetan-tetulomab (177Lu-DOTA-HH1) was evaluated. Biodistribution of 177Lu-tetraxetan-tetulomab was compared with 177Lu-tetraxetan-rituximab and free 177Lu in nude mice implanted with Daudi lymphoma xenografts. The data showed that 177Lu-tetulomab had a relevant stability and tumor targeting properties in the human lymphoma model. The half-life of 177Lu allowed significant tumor to normal tissue ratios to be obtained indicating that 177Lu-tetraxetan-tetulomab could be suitable for clinical testing. The biological and effective half-life in blood was higher for 177Lu-tetraxetan-tetulomab than for 177Lu-tetraxetan-rituximab. The biodistribution of 177Lu-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 177Lu-tetraxetan-tetuloma b and 177Lu-tetraxetan-rituximab. The absorbed radiation doses were extrapolated to human absorbed radiation doses. These extrapolated absorbed radiation doses to normal tissues for 177Lutetraxetan- 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 177Lu-tetraxetan-tetulomab in the clinic.

Keywords:

CD37, Lutetium-177, Non-Hodgkin lymphoma, Radioimmunotherapy

Affiliation:

Nordic Nanovector AS, Kjelsasveien 168 B, 0884 Oslo, Norway.



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