title: 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.
authors.affiliation: Nordic Nanovector AS, Kjelsåsveien 168 B, 0884 Oslo, Norway.
authors.forename: Ada H V
authors.initials: AH
authors.lastname: Repetto-Llamazares
authors.forename: Roy H
authors.initials: RH
authors.lastname: Larsen
authors.forename: Camilla
authors.initials: C
authors.lastname: Mollatt
authors.forename: Michael
authors.initials: M
authors.lastname: Lassmann
authors.forename: Jostein
authors.initials: J
authors.lastname: Dahle
mesh_terms: D000818:Animals; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008187:Lutetium / Q000378:metabolism / Q000493:pharmacokinetics*; D008228:Lymphoma, Non-Hodgkin / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000378:metabolism; D011829:Radiation Dosage; D011868:Radioisotopes / Q000378:metabolism / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D011868:Radioisotopes; D008187:Lutetium