Molecular Imaging of Proliferation in Malignant Lymphoma

Abstract

We have determined the ability of positron emission tomography (PET) with the thymidine analogue 3 ¶-deoxy-3 ¶-[18 F]fluorothymidine (FLT) to detect manifestation sites of malignant lymphoma, to assess proliferative activity, and to differentiate aggressive from indolent tumors. In this prospective study, FLT-PET was done additionally to routine staging procedures in 34 patients with malignant lymphoma. Sixty minutes after i.v. injection of f330 MBq FLT, emission and transmission scanning was done. Tracer uptake in lymphoma was evaluated semiquantitatively by calculation of standardized uptake values (SUV) and correlated to tumor grading and proliferation fraction as determined by Ki-67 immunohistochemistry. FLT-PET detected a total of 490 lesions compared with 420 lesions revealed by routine staging. In 11 patients with indolent lymphoma, mean FLT-SUV in biopsied lesions was 2.3 (range, 1.2-4.5). In 21 patients with aggressive lymphoma, a significantly higher FLT uptake was observed (mean FLT-SUV, 5.9; range, 3.2-9.2; P < 0.0001) and a cutoff value of SUV = 3 accurately discriminated between indolent and aggressive lymphoma. Linear regression analysis indicated significant correlation of FLT uptake in biopsied lesions and proliferation fraction (r = 0.84; P < 0.0001). In this clinical study, FLT-PET was suitable for imaging malignant lymphoma and noninvasive assessment of tumor grading. Due to specific imaging of proliferation, FLT may be a superior PET tracer for detection of malignant lymphoma in organs with high physiologic fluorodeoxyglucose uptake and early detection of progression to a more aggressive histology or potential transformation.

Predictive Value of Initial18F-FLT Uptake in Patients with Aggressive Non-Hodgkin Lymphoma Receiving R-CHOP Treatment

“…The high sensitivity for detection of aggressive lymphoma is in agreement with several previously published trials (6,10,13,25,26). Even osseous lesions were detectable 18 F-FLT uptake.…”

“…Our study is by far the largest clinical trial using 18 F-FLT PET for the characterization of aggressive lymphoma (n 5 66). A major strength of our study is a high number of patients assessed who demonstrated that proliferation imaging is a sensitive and reliable procedure potentially suitable also for initial staging of aggressive B-cell lymphoma (6,25,26).…”

“…Recently, published studies demonstrated a significant correlation of tumor cell proliferation and 18 F-FLT uptake in lymphoma and solid tumors (6)(7)(8)(9)(10)(11)(12). Preliminary studies have also shown that 18 F-FLT PET allows noninvasive assessment of tumor grading and early response assessment (6,10). Predictive markers are desirable, guiding optimal treatment in lymphoma; yet the suitability of the initial 18 F-FLT uptake has not been studied thus far.…”

18F-FDG or 3′-Deoxy-3′-18F-Fluorothymidine to Detect Transformation of Follicular Lymphoma

“…Conceptually, 39-deoxy-39-18 F-fluorothymidine ( 18 F-FLT) reflects proliferation more closely than 18 F-FDG (12,13). The limited data on 18 F-FLT PET in patients with transformed FL suggest a higher 18 F-FLT uptake in aggressive lymphoma than in indolent lymphoma, albeit with overlap (14,15).…”

Current Molecular Imaging Positron Emitting Radiotracers in Oncology

“…Several reports have been published describing the use of PET imaging of 18 F-FLT uptake as a surrogate marker for early in vivo quantitative imaging of drug-induced changes in cell proliferation. 18 F-FLT has been studied and compared with FDG in many different types of tumors including brain tumor [49], colorectal cancer [50], non-small cell lung cancer [51], esophageal cancer [52], breast cancer [53,54], and lymphoma [55].…”