David C.P. Cobben

[18F]FLT-PET in oncology: current status and opportunities

In recent years, [18F]-fluoro-3′-deoxy-3′-L-fluorothymidine ([18F]FLT) has been developed as a proliferation tracer. Imaging and measurement of proliferation with PET could provide us with a non-invasive staging tool and a tool to monitor the response to anticancer treatment. In this review, the basis of [18F]FLT as a proliferation tracer is discussed. Furthermore, an overview of the current status of [18F]FLT-PET research is given. The results of this research show that although [18F]FLT is a tracer that visualises cellular proliferation, it also has certain limitations. In comparison with the most widely used PET tracer, [18F]FDG, [18F]FLT uptake is lower in most cases. Furthermore, [18F]FLT uptake does not always reflect the tumour cell proliferation rate, for example during or shortly after certain chemotherapy regimens. The opportunities provided by, and the limitations of, [18F]FLT as a proliferation tracer are addressed in this review, and directions are given for further research, taking into account the strong and weak points of the new tracer.

Detection and grading of soft tissue sarcomas of the extremities with 18F-3'-fluoro-3'-deoxy-L-thymidine

Purpose: The aim of the study was to investigate the feasibility of 18F-3′-fluoro-3′-deoxy-l-thymidine positron emission tomography (FLT-PET) for the detection and grading of soft tissue sarcoma (STS). Experimental Design: Nineteen patients with 20 STSs of the extremities were scanned, using attenuation corrected whole-body FLT-PET. Standardized uptake values (SUVs) and tumor:nontumor ratios (TNTs) were compared with histopathological parameters using French and Japanese grading systems. Results: Mean SUV, maximal SUV, and TNT could differentiate between low-grade (grade 1; n = 6) STS and high-grade (grade 2 and 3; n = 14) STS according to the French grading system (P = 0.001). Mean SUV, max SUV, and TNT correlated with mitotic score, MIB-1 score, the French and Japanese grading system (• = 0.550–0.747). Conclusions: FLT-PET is able to visualize STS and differentiate between low-grade and high-grade STS. The uptake of FLT correlates with the proliferation of STS.

Fluorodeoxyglucose-positron emission tomography and sentinel lymph node biopsy in staging primary cutaneous melanoma

AIM We report the value of sentinel lymph node (SLN) biopsy and fluorodeoxyglucose-positron emission tomography (FDG-PET) in relation to SLN biopsy in staging primary cutaneous melanoma. METHODS Fifty-five patients with primary cutaneous melanoma >1.0 mm. Breslow thickness and no palpable regional lymph nodes underwent a FDG-PET scan before SLN biopsy. RESULTS SLNs were retrieved in 53 patients. Melanoma metastases were found in the SLN of 13 patients. FDG-PET detected the lymph node metastases in two of the 13 patients with SLN metastases. In five patients FDG accumulation was recorded in a regional lymph node basin, while no tumour positive SLN was found. In eight patients FDG-PET showed increased activity at a site of possible distant metastasis. Metastatic disease was confirmed in one patient. No explanation for the positive FDG-PET result could be found in five cases. CONCLUSION FDG-PET should not be considered in this group. SLN biopsy reveals regional metastases that are too small to be detected by FDG-PET. The prevalence of distant metastases is too small to justify routine use of FDG-PET.

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

BackgroundRadiotherapy (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. MethodsBone 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. ResultsA 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. Conclusion18F–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.

Should breathing adapted radiotherapy also be applied for right-sided breast irradiation?

Abstract Background: Voluntary moderate deep inspiration breath-hold (vmDIBH) is widely used for left sided breast cancer patients. The purpose of this study was to investigate the usefulness of vmDIBH in local and locoregional radiation therapy (RT) of right-sided breast cancer. Materials and Methods: For fourteen right-sided breast cancer patients, 3D-conformal (3D-CRT) RT plans (i.e., forward IMRT) were calculated on free-breathing (FB) 3D-CRT(FB) and vmDIBHCT-scans, for local- as well as locoregional breast treatment, with and without internal mammary nodes (IMN). Dose volume parameters were compared. Results: For local breast treatment, no relevant reduction in mean lung dose (MLD) was found. For locoregional breast treatment without IMN, the average MLD reduced from 6.5 to 5.4 Gy (p < 0.005) for the total lung and from 11.2 to 9.7 Gy (p < 0.005) for the ipsilateral lung. For locoregional breast treatment with IMN, the average MLD reduced from 10.8 to 9.1 Gy (p < 0.005) for the total lung and from 18.7 to 16.2 Gy (p < 0.005) for the ipsilateral lung, whilea small reduction in mean heart dose of 0.4 Gy (p = 0.07) was also found. Conclusions: Breathing adapted radiation therapy in left-sided breast cancer patients is becoming widely introduced. As a result of the slight reduction in lung dose found for locoregional right-sided breast cancer treatment in this study, a slightly lower risk of pneumonitis and secondary lung cancer (in ever smoking patients) can be expected.In addition, for some patients the heart dose will also be reduced by more than 0.5 up to 2.6 Gy. We therefore suggest to also apply breath-hold for locoregional irradiation of right-sided breast cancer patients.