title: Phase 1 trial study of 131I-labeled chimeric 81C6 monoclonal antibody for the treatment of patients with non-Hodgkin lymphoma.
abstract: We report a phase 1 study of pharmacokinetics, dosimetry, toxicity, and response of (131)I anti-tenascin chimeric 81C6 for the treatment of lymphoma. Nine patients received a dosimetric dose of 370 MBq (10 mCi). Three patients received an administered activity of 1480 MBq (40 mCi), and 2 developed hematologic toxicity that required stem cell infusion. Six patients received an administered activity of 1110 MBq (30 mCi), and 2 developed toxicity that required stem cell infusion. The clearance of whole-body activity was monoexponential with a mean effective half-life of 110 hours (range, 90-136 hours) and a mean effective whole-body residence time of 159 hours (range, 130-196 hours). There was rapid uptake within the viscera; however, tumor uptake was slower. Activity in normal viscera decreased proportional to the whole body; however, tumor sites presented a slow clearance (T(1/2), 86-191 hours). The mean absorbed dose to whole-body was 67 cGy (range, 51-89 hours), whereas the dose to tumor sites was 963 cGy (range, 363-1517 cGy). Despite lack of a "blocking" antibody, 1 of 9 patients attained a complete remission and 1 a partial remission. These data demonstrate this radiopharmaceutical to be an encouraging agent for the treatment of lymphoma particularly if methods to protect the normal viscera are developed.
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA. rizzi003@mc.duke.edu
authors.forename: David A
authors.initials: DA
authors.lastname: Rizzieri
authors.forename: Gamal
authors.initials: G
authors.lastname: Akabani
authors.forename: Michael R
authors.initials: MR
authors.lastname: Zalutsky
authors.forename: R Edward
authors.initials: RE
authors.lastname: Coleman
authors.forename: Scott D
authors.initials: SD
authors.lastname: Metzler
authors.forename: James E
authors.initials: JE
authors.lastname: Bowsher
authors.forename: Bonnie
authors.initials: B
authors.lastname: Toaso
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Anderson
authors.forename: Anand
authors.initials: A
authors.lastname: Lagoo
authors.forename: Steve
authors.initials: S
authors.lastname: Clayton
authors.forename: Charles N
authors.initials: CN
authors.lastname: Pegram
authors.forename: Joseph O
authors.initials: JO
authors.lastname: Moore
authors.forename: Jon P
authors.initials: JP
authors.lastname: Gockerman
authors.forename: Carlos
authors.initials: C
authors.lastname: DeCastro
authors.forename: Cristina
authors.initials: C
authors.lastname: Gasparetto
authors.forename: Nelson J
authors.initials: NJ
authors.lastname: Chao
authors.forename: Darell D
authors.initials: DD
authors.lastname: Bigner
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000633:toxicity*; D001692:Biological Transport; D001706:Biopsy; D001853:Bone Marrow / Q000473:pathology; D005260:Female; D006801:Humans; D000922:Immunotoxins / Q000493:pharmacokinetics / Q000633:toxicity; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics / Q000633:toxicity*; D008198:Lymph Nodes / Q000473:pathology; D008228:Lymphoma, Non-Hodgkin / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D051379:Mice; D018579:Patient Selection; D019063:Tenascin / Q000032:analysis; D014018:Tissue Distribution; D014057:Tomography, X-Ray Computed
chemical_list: D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D007457:Iodine Radioisotopes; D019063:Tenascin