title: In vivo imaging of radiation-induced apoptosis in follicular lymphoma patients.
abstract: OBJECTIVE
  To evaluate (99m)Tc-Annexin-V (TAV) scintigraphy in monitoring radiation-induced apoptotic cell death in follicular lymphoma (FL) patients.
  
  
  METHODS
  Eleven FL patients (7 female and 4 male; median age, 58 years; range, 42-80 years) with recurrent disease underwent TAV imaging before and 24 hours after the last fraction of the 2 x 2 Gy involved field radiotherapy regimen. Fine-needle aspiration cytology was performed on 5 consecutive days to determine the optimal time window for apoptosis detection and to confirm the apoptotic nature of the response. The TAV scintigraphy (total body studies and SPECT of the irradiated sites) was performed 4 hours after the administration of the radiopharmaceutical. Tumor uptake was scored in a semiquantitative manner as absent (-) weak (+/-), present (+), or intense (++) with corresponding categories for the cytologic slides. Response evaluation was performed after 1 week and 4 weeks both in terms of completeness and speed of remission.
  
  
  RESULTS
  Baseline TAV uptake was absent in 6 and weak in 5 patients. Sequential cytology indicated that the optimal time period for apoptosis assessment was between 24 and 48 hours after the last fraction of the 2 x 2 Gy regimen. Baseline cytology was concordant with baseline TAV in all patients. Apoptotic feature appearance (nuclear chromatin condensation, margination and apoptotic body formation) after low-dose irradiation matched the irradiation response in all patients. In all but 1 patient the posttreatment TAV uptake matched the posttreatment cytology. In these 10 patients the cytology and TAV results correlated with the type and onset of the clinical response.
  
  
  CONCLUSIONS
  Tumor (99m)Tc-Annexin-V uptake can be increased after 2 x 2 Gy involved field radiotherapy. This increase was concordant with the appearance of apoptotic morphology as determined by cytology, and correlated with the clinical outcome. Apoptotic cell death can be observed on Day 4 of this regimen and if so predicts a complete remission within 1 week.
authors.affiliation: Department of Radiotherapy, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. r.haas@nki.nl
authors.forename: Rick L M
authors.initials: RL
authors.lastname: Haas
authors.forename: Daphne
authors.initials: D
authors.lastname: de Jong
authors.forename: Renato A
authors.initials: RA
authors.lastname: Valdés Olmos
authors.forename: Cees A
authors.initials: CA
authors.lastname: Hoefnagel
authors.forename: Iris
authors.initials: I
authors.lastname: van den Heuvel
authors.forename: Shuraila F
authors.initials: SF
authors.lastname: Zerp
authors.forename: Harry
authors.initials: H
authors.lastname: Bartelink
authors.forename: Marcel
authors.initials: M
authors.lastname: Verheij
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017304:Annexin A5; D017209:Apoptosis; D044963:Biopsy, Fine-Needle; D005260:Female; D006801:Humans; D008224:Lymphoma, Follicular / Q000000981:diagnostic imaging / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D015609:Organotechnetium Compounds; D011446:Prospective Studies; D012008:Recurrence; D012074:Remission Induction; D013997:Time Factors; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D017304:Annexin A5; D015609:Organotechnetium Compounds; C417036:technetium Tc 99m annexin V