title: In vivo distribution of avidin-conjugated MX35 and (211)At-labeled, biotinylated poly-L-lysine for pretargeted intraperitoneal α-radioimmunotherapy.
abstract: OBJECTIVE
  Avidin-coupled monoclonal antibody MX35 (avidin-MX35) and astatine-211-labeled, biotinylated, succinylated poly-l-lysine ((211)At-B-PL(suc)) were administered in mice to assess potential efficacy as an intraperitoneal (i.p.) therapy for microscopic tumors. We aimed to establish a timeline for pretargeted radioimmunotherapy using these substances, and estimate the maximum tolerable activity.
  
  
  METHODS
  (125)I-avidin-MX35 and (211)At-B-PL(suc) were administered i.p. in nude mice. Tissue distributions were studied at various time points and mean absorbed doses were estimated from organ uptake of (211)At-B-PL(suc). Studies of myelotoxicity were performed after administration of different activities of (211)At-B-PL(suc).
  
  
  RESULTS
  We observed low blood content of both (125)I-avidin-MX35 and (211)At-B-PL(suc), indicating fast clearance. After sodium perchlorate blocking, the highest (211)At uptake was found in kidneys. Red bone marrow (RBM) accumulated some (211)At activity. Mean absorbed doses of special interest were 2.3 Gy/MBq for kidneys, 0.4 Gy/MBq for blood, and 0.9 Gy/MBq for RBM. An absorbed dose of 0.9 Gy to the RBM was found to be safe. These values suggested that RBM would be the key dose-limiting organ in the proposed pretargeting scheme, and that blood data alone was not sufficient for predicting its absorbed dose.
  
  
  CONCLUSIONS
  To attain a favorable distribution of activity and avoid major toxicities, at least 1.0 MBq of (211)At-B-PL(suc) can be administered 24 hours after an i.p. injection of avidin-MX35. These results provide a basis for future i.p. therapy studies in mice of microscopic ovarian cancer.
authors.affiliation: Department of Radiation Physics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. sofia.frost@radfys.gu.se
authors.forename: Sofia Helena Linnea
authors.initials: SH
authors.lastname: Frost
authors.forename: Tom
authors.initials: T
authors.lastname: Bäck
authors.forename: Nicolas
authors.initials: N
authors.lastname: Chouin
authors.forename: Holger
authors.initials: H
authors.lastname: Jensen
authors.forename: Ragnar
authors.initials: R
authors.lastname: Hultborn
authors.forename: Lars
authors.initials: L
authors.lastname: Jacobsson
authors.forename: Sture
authors.initials: S
authors.lastname: Lindegren
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D001246:Astatine / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D001360:Avidin / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D019921:Biotinylation / Q000379:methods; D001853:Bone Marrow / Q000187:drug effects; D005260:Female; D007456:Iodine Isotopes / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D007553:Isotope Labeling / Q000379:methods; D007668:Kidney / Q000187:drug effects; D008239:Lysine / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000532:radiotherapy; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D016499:Radioimmunotherapy / Q000379:methods*; D014018:Tissue Distribution
chemical_list: D000911:Antibodies, Monoclonal; D007456:Iodine Isotopes; D011108:Polymers; D001360:Avidin; D008239:Lysine; D001246:Astatine