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

Ada H V Repetto-Llamazares, Roy H Larsen, Camilla Mollatt, Michael Lassmann, Jostein Dahle, Ada H V Repetto-Llamazares, Roy H Larsen, Camilla Mollatt, Michael Lassmann, Jostein Dahle

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.

Figures

Fig. (1)
Fig. (1)
Biodistribution (kBq/g) of 177Lu-tetulomab (A) and 177Lurituximab (B) in female nude mice with Daudi tumor xenografts. The data were normalized to an injected activity of 1 MBq per mouse (40 MBq/kg). Error bars correspond to standard error.
Fig. (2)
Fig. (2)
Dose rate (mGy/h) for key organs estimated from biodistributions of 177Lu-tetulomab (A) and 177Lu-rituximab (B) in nude mice with Daudi xenografts. The data were normalized to an injected activity of 1 MBq per mouse (40 MBq/kg). Error bars correspond to standard error.
Fig. (3)
Fig. (3)
Dose (Gy) to normal organs for mice with xenografts injected with 177Lu-tetulomab or 177Lu-rituximab. The data were normalized to an injected activity of 1 MBq per mouse (40 MBq/kg). Error bars correspond to standard error.

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