title: Performance of immuno-positron emission tomography with zirconium-89-labeled chimeric monoclonal antibody U36 in the detection of lymph node metastases in head and neck cancer patients.
abstract: OBJECTIVE
  Immuno-positron emission tomography (PET), the combination of PET with monoclonal antibodies (mAb), is an attractive option to improve tumor detection and to guide mAb-based therapy. The long-lived positron emitter zirconium-89 ((89)Zr) has ideal physical characteristics for immuno-PET with intact mAbs but has never been used in a clinical setting. In the present feasibility study, we aimed to evaluate the diagnostic imaging performance of immuno-PET with (89)Zr-labeled-chimeric mAb (cmAb) U36 in patients with squamous cell carcinoma of the head and neck (HNSCC), who were at high risk of having neck lymph node metastases.
  
  
  METHODS
  Twenty HNSCC patients, scheduled to undergo neck dissection with or without resection of the primary tumor, received 75 MBq (89)Zr coupled to the anti-CD44v6 cmAb U36 (10 mg). All patients were examined by computed tomography (CT) and/or magnetic resonance imaging (MRI) and immuno-PET before surgery. Six patients also underwent PET with (18)F-fluoro-2-deoxy-d-glucose. Immuno-PET scans were acquired up to 144 hours after injection. Diagnostic findings were recorded per neck side (left or right) as well as per lymph node level (six levels per side), and compared with histopathologic outcome. For this purpose, the CT/MRI scores were combined and the best of both scores was used for analysis.
  
  
  RESULTS
  Immuno-PET detected all primary tumors (n = 17) as well as lymph node metastases in 18 of 25 positive levels (sensitivity 72%) and in 11 of 15 positive sides (sensitivity 73%). Interpretation of immuno-PET was correct in 112 of 121 operated levels (accuracy 93%) and in 19 of 25 operated sides (accuracy 76%). For CT/MRI, sensitivities of 60% and 73% and accuracies of 90% and 80% were found per level and side, respectively. In the six patients with seven tumor-involved neck levels and sides, immuno-PET and (18)F-fluoro-2-deoxy-d-glucose PET gave comparable diagnostic results.
  
  
  CONCLUSIONS
  In this study, immuno-PET with (89)Zr-cmAb U36 performed at least as good as CT/MRI for detection of HNSCC lymph node metastases.
authors.affiliation: Department of Otolaryngology/Head and Neck Surgery, Nuclear Medicine and Positron Emission Tomography Research, Radiology, Amsterdam, The Netherlands. gams.vandongen@VUmc.nl
authors.forename: Pontus K E
authors.initials: PK
authors.lastname: Börjesson
authors.forename: Yvonne W S
authors.initials: YW
authors.lastname: Jauw
authors.forename: Ronald
authors.initials: R
authors.lastname: Boellaard
authors.forename: Remco
authors.initials: R
authors.lastname: de Bree
authors.forename: Emile F I
authors.initials: EF
authors.lastname: Comans
authors.forename: Jan C
authors.initials: JC
authors.lastname: Roos
authors.forename: Jonas A
authors.initials: JA
authors.lastname: Castelijns
authors.forename: Maria J W D
authors.initials: MJ
authors.lastname: Vosjan
authors.forename: J Alain
authors.initials: JA
authors.lastname: Kummer
authors.forename: C René
authors.initials: CR
authors.lastname: Leemans
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Lammertsma
authors.forename: Guus A M S
authors.initials: GA
authors.lastname: van Dongen
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000556:secondary / Q000601:surgery; D005189:False Positive Reactions; D005260:Female; D019788:Fluorodeoxyglucose F18; D006258:Head and Neck Neoplasms / Q000175:diagnosis* / Q000556:secondary / Q000601:surgery; D006801:Humans; D007553:Isotope Labeling; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D037981:Neck Dissection; D049268:Positron-Emission Tomography / Q000379:methods*; D011868:Radioisotopes; D012680:Sensitivity and Specificity; D015040:Zirconium
chemical_list: D000911:Antibodies, Monoclonal; D011868:Radioisotopes; D019788:Fluorodeoxyglucose F18; D015040:Zirconium