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18F-FDG or 18F-FLT to detect transformation
Introduction
Follicular lymphoma (FL) is the most common form of indolent B-cell non-Hodgkin’s
lymphoma accounting for about 30% of all non-Hodgkin’s lymphomas. Its clinical 2 course varies and is characterized by repeated but transient responses to therapy.
Histological transformation into an aggressive lymphoma occurs in 17%, 28% and
37% of FL patients after 5,10 and 15 years respectively, with an apparent plateau at
15 years after which transformation rarely seems to occur (1). There is increasing
evidence that autologous consolidation of transformed lymphoma patients as
first line treatment may improve survival (2-4). Furthermore, retrospective analyses
suggest that patients can be cured more often when transformation is diagnosed at
an early stage (5,6). Consequently, correct and early diagnosis is a prerequisite for
adequate treatment of patients with transformed lymphoma. Transformation can be
heralded by rapid growth of lymph nodes, an elevated lactate dehydrogenase (LDH)
and/or development of systemic symptoms (7). Histology remains the gold standard,
defining transformation as the presence of sheets of blastic cells or frank diffuse large
B cell lymphoma (DLBCL) in a patient diagnosed with FL. Therefore, it is mandatory
to biopsy at the slightest suspicion of transformation. However, since transformation
may not involve all lymph nodes, sampling errors can lead to a significant diagnostic
delay.
This problem might be overcome by the use of Positron Emission Tomography (PET) as
this technique allows for whole body tissue characterization, enabling determination
of areas of high metabolic or proliferative activity. Currently, 18-fluorodeoxyglucose
(18F-FDG) PET is used for staging and response evaluation both in aggressive, as well
as in more indolent types of lymphoma (8). There is a clear trend towards higher
18F-FDG uptake in more aggressive histological subtypes. Therefore a high uptake in an
indolent lymphoma could support the suspicion of transformation. However, there is a
considerable overlap in 18F-FDG uptake between aggressive and indolent lymphomas
potentially impairing its utility to detect transformation (9-11). In order to overcome this,
alternative tracers might be useful. Conceptually, fluorothymidine (18F-FLT) reflects
proliferation more closely than 18F-FDG (12,13). The limited data on 18F-FLT-PET in
patients with transformed FL suggest a higher 18F-FLT uptake in aggressive lymphoma
as compared to indolent lymphoma, albeit with overlap (14,15).
Studies on the role of PET in detection of transformation typically comprise a spectrum
of histological subtypes, reporting considerable variability in uptake of 18F-FDG.
However, since 18F-FDG uptake may strongly vary among histological subtypes of
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