Imaging Proliferation to Monitor Early Response of Lymphoma to Cytotoxic Treatment

Overview

Journal Mol Imaging Biol

Publisher Springer

Specialties Molecular Biology
Radiology

Date 2008 Aug 16

PMID 18704591

Citations 5

Authors

Nicolas Graf

Ken Herrmann

Jurgen Den Hollander

Falko Fend

Tibor Schuster

Hans-Jurgen Wester

Reingard Senekowitsch-Schmidtke

Christian Meyer Zum Buschenfelde

Christian Peschel

Markus Schwaiger

Tobias Dechow

Andreas K Buck

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

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[18F]FLT is superior to [18F]FDG for predicting early response to antiproliferative treatment in high-grade lymphoma in a dose-dependent manner.

Graf N, Herrmann K, Numberger B, Zwisler D, Aichler M, Feuchtinger A Eur J Nucl Med Mol Imaging. 2012; 40(1):34-43.

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