In vivo imaging of radiation-induced apoptosis in follicular lymphoma patients.
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.
Haas
Rick L M
RL
Department of Radiotherapy, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. r.haas@nki.nl
de Jong
Daphne
D
Valdés Olmos
Renato A
RA
Hoefnagel
Cees A
CA
van den Heuvel
Iris
I
Zerp
Shuraila F
SF
Bartelink
Harry
H
Verheij
Marcel
M
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
D017304:Annexin A5; D015609:Organotechnetium Compounds; C417036:technetium Tc 99m annexin V