title: A 3-step pretargeting strategy to image infection.
abstract: A new 3-step approach to imaging infectious and inflammatory foci was developed and optimized in a rat model. The approach relies on the nonspecific localization of an anti-diethylenetriaminepentaacetic acid (DTPA) antibody in inflamed tissue. In this study, the 3-step strategy was optimized by selecting the most suitable radiolabeled hapten and tuning the dosing schedule.
  
  
  METHODS
  Wistar rats with Staphylococcus aureus infection in the left calf muscle were primed with the anti-DTPA antibody DTIn-1 (0.67, 2, or 6 nmol per rat). In the second step (1-24 h later), the anti-DTPA activity in the circulation was blocked with unlabeled bovine serum albumin DTPA-In (0.3, 1, or 3 nmol per rat). In the third step (5-30 min later), the radiolabeled hapten (monovalent or bivalent 111In-DTPA) was administered. The in vivo distribution of the radiolabel was monitored by scintigraphic imaging and by ex vivo counting of dissected tissues.
  
  
  RESULTS
  Scatchard analysis revealed that the affinity of DTIn-1 for bivalent DTPA-111In (111In-diDTPA) was 6 times higher than the affinity for monovalent 111In-DTPA (K(a) = 0.87 x 10(-9) mol/L vs. 5.3 x 10(-9) mol/L). The uptake of the bivalent chelate in the abscess was 2.5-fold higher than that of monovalent 111In-DTPA. Most important, the bivalent chelate was completely retained in the abscess over time. Using the bivalent chelate, the optimal dosing scheme was determined with respect to the DTIn-1 dose (2 nmol per rat), the blocking agent dose (1 nmol per rat), and radiolabeled chelate dose (40 pmol per rat). The procedure was rapid; the infectious focus was clearly visualized 1 h after injection of the 111In-labeled diDTPA, which was 5 h after administration of the anti-DTPA antibody. The nontargeted radiolabel rapidly cleared to the urine, only being retained in the abscess and the kidneys (4-6 percentage injected dose). Finally, an N2S2 core was attached to the diDTPA compound, allowing the use of 99mTc.
  
  
  CONCLUSIONS
  This 3-step approach enables rapid imaging of infectious foci with minimal uptake in noninflamed tissues.
authors.affiliation: Department of Nuclear Medicine, University Hospital Nijmegen, Nijmegen, The Netherlands.
authors.forename: O C
authors.initials: OC
authors.lastname: Boerman
authors.forename: J
authors.initials: J
authors.lastname: van Eerd
authors.forename: W J
authors.initials: WJ
authors.lastname: Oyen
authors.forename: F H
authors.initials: FH
authors.lastname: Corstens
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D006241:Haptens; D007074:Immunoglobulin G; D007205:Indium Radioisotopes; D008297:Male; D016719:Radioimmunodetection / Q000379:methods*; D019275:Radiopharmaceuticals; D051381:Rats; D017208:Rats, Wistar; D012710:Serum Albumin, Bovine; D013203:Staphylococcal Infections / Q000000981:diagnostic imaging*; D018709:Statistics, Nonparametric; D016284:Technetium Tc 99m Pentetate; D014018:Tissue Distribution
chemical_list: D000911:Antibodies, Monoclonal; D006241:Haptens; D007074:Immunoglobulin G; D007205:Indium Radioisotopes; D019275:Radiopharmaceuticals; D012710:Serum Albumin, Bovine; D016284:Technetium Tc 99m Pentetate