Publikation

Imaging proliferation to monitor early response of lymphoma to cytotoxic treatment

Wissenschaftlicher Artikel/Review - 14.08.2008

Bereiche
PubMed
DOI

Zitation
Graf N, Dechow T, Schwaiger M, Peschel C, zum Büschenfelde C, Senekowitsch-Schmidtke R, Wester H, Schuster T, Fend F, den Hollander J, Herrmann K, Buck A. Imaging proliferation to monitor early response of lymphoma to cytotoxic treatment. Mol Imaging Biol 2008; 10:349-55.
Art
Wissenschaftlicher Artikel/Review (Englisch)
Zeitschrift
Mol Imaging Biol 2008; 10
Veröffentlichungsdatum
14.08.2008
ISSN (Druck)
1536-1632
Seiten
349-55
Kurzbeschreibung/Zielsetzung

PURPOSE
Positron emission tomography with the thymidine analogue 3'-deoxy-3'-[18F]fluorothymidine (FLT) has been reported to closely reflect lymphoma proliferation in vivo. In this preclinical study, we have investigated if FLT can also be utilized for imaging therapy-induced alterations of the nucleoside metabolism and if FLT is a surrogate marker for early response to cytotoxic treatment.

MATERIALS AND METHODS
Immunodeficient mice bearing high-grade lymphoma xenotransplants were treated with the cytotoxic agent doxorubicin (day 0). In the time course of day +1 to +9, antiproliferative effects were assessed non-invasively with FLT-PET and correlated to changes of the proliferation fraction and induction of apoptosis, as assessed by immunohistochemistry.

RESULTS
Tumor growth in untreated animals was significantly higher than in treated animals. In FLT-PET scans, these observations correlated with a significant decrease of tumor-to-background ratio in the therapy group already at day 1. Likewise, median tumor-to-muscle ratio of FLT uptake already declined at day 1. The proliferation fraction assessed by Ki-67 immunohistochemistry decreased after chemotherapy, while activated caspase 3 increased, suggesting both cell cycle arrest and induction of apoptosis as underlying mechanisms of the observed PET-signal alterations.

CONCLUSION
In a lymphoma xenotransplant model, we show that positron emission tomography using the proliferation marker FLT is suitable to detect early response to cytotoxic treatment. A significant decrease of FLT uptake but not tumor growth was detectable already 24 h after therapy and correlated with reduced proliferation and induction of apoptosis. Thus, FLT-PET has a potential for imaging early response to treatment in malignant lymphoma.