Effect of radiotherapy and chemotherapy on bone marrow activity: a 18F-FLT-PET study

Radiotherapy (RT) and chemotherapy are important treatment modalities for a variety of malignant tumor types. During therapy for malignant diseases, often the limitation for further therapy is determined by the capability of the bone marrow to withstand radiochemotherapeutic effects. Evaluation of hematologic toxicity is commonly performed with peripheral blood counts, and occasionally, sampling of marrow through a bone marrow biopsy. Neither method provides a comprehensive assessment, as bone marrow biopsy is invasive, and both are subject to sampling variability. Fluorine-18-3'-fluoro-3'-deoxy-L-thymidine-PET (18F-FLT-PET) is a noninvasive method and related to the rate of DNA synthesis and visualizes the high cycling activity of hematopoietic cells in the bone marrow compartment. To prove the clinical consistency of marrow function and imaging, we investigated populations of patients typically seen in clinical practice, after radiation and chemotherapy. In this feasibility study, patients were evaluated (i) to prove the ability of visualization and quantification of the activity of the bone marrow compartment with 18F-FLT-PET and (ii) to examine the effect of RT and chemotherapy on bone marrow activity and the correlation with clinical findings.

Bone marrow activity in the cervical region of 10 patients with laryngeal carcinoma who received a mean total dose of 68 Gy (range 30-41 fractions) was evaluated with 18F-FLT-PET, before and 1 month after RT. Whole body FLT images were assessed in nine patients with nonseminomatous testicular germ cell tumor, before and 6 months after the last chemotherapy, consisting of four courses of bleomycin, cisplatin, and etoposide. The maximum standardized uptake value (SUVmax) was used to quantify FLT uptake in bone marrow at the standard bone marrow regions.

A significant decrease in 18F-FLT-PET uptake was observed in all the studied laryngeal carcinoma patients in the cervical region after RT of the adjacent bone marrow compartment. Tumor stage and additional field-of-view of RT were inversely related to the 18F-FLT uptake in bone marrow. The mean 18F-FLT SUVmax before RT was 3.0+/-1.34 and after RT was 1.94+/-0.60 (P=0.013). The mean 18F-FLT SUVmax of the spine (Th5-Th12) regions outside the field-of-view of RT were stable and reproducible and not significantly different (5.56+/-1.56 vs. 5.16+/-1.35, P=0.16). Chemotherapy did not result in a significant difference of whole body SUVmax value, with a mean SUVmax of 4.99+/-1.15 prechemotherapy, and a mean SUVmax of 5.28+/-1.0 postchemotherapy (P=0.21). Laboratory analysis of the hematologic parameters confirmed repopulation of the bone marrow.

18F-FLT uptake in the bone marrow decreases after RT, but not after chemotherapy. We conclude that 18F-FLT-PET is a potential noninvasive tool that can be used in the assessment of quantification of cellular division in the hematopoietic organ.