Abstract
Although 3′-deoxy-3′[(18)F]-fluorothymidine (FLT)-positron emission tomography (PET) has been utilized for tumor response assessment to neoadjuvant chemotherapy in soft tissue sarcomas, it has not been exploited for the assessment of early response to systematically targeted therapies. Herein, we investigated the 18F-FLT PET/CT kinetics in patients with sarcoma who received targeted therapies. Among 15 patients with sarcoma who underwent 18F-FLT PET/CT, 5 patients (33%) patients were imaged at three time points: At baseline and at 1–15 weeks (MDM2-inhibitor treatment), and 10 patients (67%) were imaged twice: At baseline and at 1–4 weeks (MDM2 inhibitor, n = 5; c-met inhibitor n = 5). The patients with sarcoma had a total of 18 identifiable tumors. Twelve of 15 patients (80%) demonstrated 18F-FLT concentrations changes early, i.e., at 1–4 weeks. Eight patients responded (53.3%), four patients progressed (26.7%) based on FLT change of more than 10% increase, and three patients (20%) demonstrated no change. 18F-FLT PET/CT may be used for early response imaging to molecularly targeted therapies in patients with sarcoma. Further larger studies in specific sarcoma sub-types are warranted.
Highlights
Tumor proliferation and early response to molecularly targeted therapy can be imaged using positron emission tomography (18 F-FLT PET/CT) [1,2,3,4,5].Fluorine-18 fluorothymidine (18 F-FLT) is a structural analog of the DNA component, thymidine; it is not incorporated into the DNA
The advantage of 18 F-FLT is that, it is a marker of tumor proliferation and its uptake has been shown to be proportional to the DNA synthesis rate and correlative with proliferative index [1]
A baseline 18 F-FLT PET/CT was obtained before treatment with MDM2 or C-MET inhibitor followed by a second 18 F-FLT PET/CT approximately 1–15 weeks after treatment in all participants (Tables 1 and 2)
Summary
Tumor proliferation and early response to molecularly targeted therapy can be imaged using positron emission tomography (18 F-FLT PET/CT) [1,2,3,4,5]. Fluorine-18 fluorothymidine (18 F-FLT) is a structural analog of the DNA component, thymidine; it is not incorporated into the DNA. It is entrapped in the cell due to phosphorylation by thymidine kinase, a part of the proliferation pathway. This is trapped in the cell and accumulates in the cell. Imaging of cellular proliferation has the potential to become an important diagnostic and/or theranostic tool to evaluate the tumor growth rates, and objectively assess potential response to treatment [1]
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