Investigation of the pharmacokinetics of 3'-deoxy-3'-[18F]fluorothymidine uptake in the bone marrow before and early after initiation of chemoradiation therapy in head and neck cancer

Abstract

Introduction: The kinetics of the bone marrow uptake of 3'-deoxy-3'-[(18)F]fluorothymidine (FLT) before and early after initiation of chemoradiation therapy was investigated in patients with head and neck cancer.

Methods: Fourteen subjects with head and neck cancer underwent FLT positron emission tomography (PET) at baseline and after 10 Gy of radiation therapy. Thirteen subjects also received one cycle of platinum-based chemotherapy before the second FLT PET. Kinetic parameters, including the flux constant based on compartmental analysis (K(FLT)) and the Patlak constant (K(Patlak)) for cervical marrow, were calculated. Standardized uptake values (SUVs) for the cervical marrow (inside the radiation field) and lumbar spine marrow (outside the radiation field) were also determined.

Results: There was a significant drop in FLT uptake in the bone marrow inside the radiation field. Mean pretreatment uptake values for the cervical spine were SUV=3.08+/-0.66, K(FLT)=0.045+/-0.016 min(-1) and K(Patlak)=0.039+/-0.013 min(-1). After treatment, these values were SUV=0.74+/-0.19, K(FLT)=0.011+/-0.005 min(-1) and K(Patlak)=0.005+/-0.002 min(-1). Compartmental analysis revealed a significant drop in k(3) in irradiated cervical marrow. FLT uptake in the bone marrow outside the radiation field exhibited a significantly smaller decrease.

Conclusions: There is a marked decrease in FLT uptake in irradiated bone marrow after 10 Gy of radiation therapy to the head and neck. The drop in FLT uptake in irradiated marrow is due to a significant decrease in the net phosphorylation rate of FLT.

(c( 2010 Elsevier Inc. All rights reserved.

Figures

Figure 1

FLT PET images pretherapy (A and C) and midtherapy (B and D), both obtained scan at approximately 75 minutes after the intravenous administration of 181 MBq of FLT. Note the disappearance of FLT uptake in the cervical spine and upper thoracic spine on sagittal images (A and B). The representative transaxial images (C and D) also show the drop in FLT uptake in the bone marrow (arrow) and right tonsillar squamous cell carcinoma (dashed arrow) after therapy.

Figure 2

FLT uptake in the cervical spine and lumbar spine bone marrow pretherapy and after 10 Gy of radiation therapy and one cycle of platinum-based chemotherapy. (i.e., midtherapy). Subject H did not receive chemotherapy prior to the midtherapy FLT PET scan.

Figure 3

Mean FLT uptake in cervical bone marrow over 60 minutes of dynamic imaging pretherapy (open diamonds) and midtherapy (X). Early stages of the dynamic uptake curves are similar indicating no significant change in initial FLT uptake with therapy. The significant difference in the curves after the initial 5 min reflects the drop in retention of FLT in the bone marrow after treatment due to decrease in phosphorylation (k3).