title: Pretargeted immuno-PET and radioimmunotherapy of prostate cancer with an anti-TROP-2 x anti-HSG bispecific antibody.
abstract: OBJECTIVE
  TF12 is a trivalent bispecific antibody that consists of two anti-TROP-2 Fab fragments and one anti-histamine-succinyl-glycine (HSG) Fab fragment. The TROP-2 antigen is found in many epithelial cancers, including prostate cancer (PC), and therefore this bispecific antibody could be suitable for pretargeting in this cancer. In this study, the characteristics and the potential for pretargeted radioimmunoimaging and radioimmunotherapy with TF12 and the radiolabeled di-HSG peptide IMP288 in mice with human PC were investigated.
  
  
  METHODS
  The optimal TF12 protein dose, IMP288 peptide dose, and dose interval for PC targeting were assessed in nude mice with s.c. PC3 xenografts. Immuno-positron emission tomography (PET)/CT was performed using TF12/⁶⁸Ga-IMP288 at optimized conditions. The potential of pretargeted radioimmunotherapy (PRIT) using the TF12 pretargeted ¹⁷⁷Lu-IMP288 was determined.
  
  
  RESULTS
  TF12 and ¹¹¹In-IMP288 showed high and fast accumulation in the tumor [20.4 ± 0.6%ID/g at 1 h post-injection (p.i.)] at optimized conditions, despite the internalizing properties of TF12. The potential for PRIT was shown by retention of 50% of the ¹¹¹In-IMP288 in the tumor at 48 h p.i. One cycle of treatment with TF12 and ¹⁷⁷Lu-IMP288 showed significant improvement of survival compared to treatment with ¹⁷⁷Lu-IMP288 alone (90 vs. 67 days, p<0.0001) with no renal or hematological toxicity.
  
  
  CONCLUSIONS
  TROP-2-expressing PC can be pretargeted efficiently with TF12, with very rapid uptake of the radiolabeled hapten-peptide, IMP288, sensitive immuno-PET, and effective therapy.
authors.affiliation: Department of Nuclear Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. k.vanrij@akf.umcn.nl
authors.forename: Catharina M
authors.initials: CM
authors.lastname: van Rij
authors.forename: Susanne
authors.initials: S
authors.lastname: Lütje
authors.forename: Cathelijne
authors.initials: C
authors.lastname: Frielink
authors.forename: Robert M
authors.initials: RM
authors.lastname: Sharkey
authors.forename: David M
authors.initials: DM
authors.lastname: Goldenberg
authors.forename: Gerben M
authors.initials: GM
authors.lastname: Franssen
authors.forename: William J
authors.initials: WJ
authors.lastname: McBride
authors.forename: Edmund A
authors.initials: EA
authors.lastname: Rossi
authors.forename: Wim J G
authors.initials: WJ
authors.lastname: Oyen
authors.forename: Otto C
authors.initials: OC
authors.lastname: Boerman
mesh_terms: D000818:Animals; D018033:Antibodies, Bispecific / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D006573:Heterocyclic Compounds, 1-Ring / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009842:Oligopeptides / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging* / Q000532:radiotherapy; D011485:Protein Binding; D016499:Radioimmunotherapy; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics* / Q000627:therapeutic use; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D018033:Antibodies, Bispecific; D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; C515662:DOTA-tyrosyl-lysyl(histaminyl-succinyl-glycyl)-glutamyl-lysyl(histaminyl-succinyl-glycyl)amide; D006573:Heterocyclic Compounds, 1-Ring; D009842:Oligopeptides; D019275:Radiopharmaceuticals; C499380:TACSTD2 protein, human