F-18 FLT PET: a noninvasive diagnostic tool for visualization of the bone marrow compartment in patients with aplastic anemia: a pilot study.

RATIONALE: A discordant relationship between bone marrow cellularity and peripheral blood findings is regularly noticed in patients with aplastic anemia (AA). Therefore, the feasibility of 3-F-18 fluoro-3-deoxy-L-thymidine (F-18 FLT PET was tested as a noninvasive tool to visualize the total distribution of the hematopoietic bone marrow compartment in AA at presentation or after treatment. METHODS: In vivo scanning was performed with F-18 FLT PET in AA patients (n = 17), including patients upfront (n = 11) and following treatment (n = 6), in addition to peripheral blood cell counts and a bone marrow biopsy. RESULTS: A striking abnormal F-18 FLT scan was observed in all patients upfront treatment, in particular a reduced uptake of the pelvis was shown, the area that is biopsied for the bone marrow biopsy. Following treatment, the number of solitary lesions with increased proliferative activity outside the pelvis was noticed in patients with partial response, whereas patients with a complete remission showed a homogenous uptake throughout the skeleton. CONCLUSION: This pilot study demonstrates that F-18 FLT scan provides a highly distinctive overview of the bone marrow compartment in AA that might be helpful for making a proper diagnosis and monitoring treatment response of AA patients.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Radionuclide imaging of bone marrow disorders.

Noninvasive imaging techniques have been used in the past for visualization the functional activity of the bone marrow compartment. Imaging with radiolabelled compounds may allow different bone marrow disorders to be distinguished. These imaging techniques, almost all of which use radionuclide-labelled tracers, such as (99m)Tc-nanocolloid, (99m)Tc-sulphur colloid, (111)In-chloride, and radiolabelled white blood cells, have been used in nuclear medicine for several decades. With these techniques three separate compartments can be recognized including the reticuloendothelial system, the erythroid compartment and the myeloid compartment. Recent developments in research and the clinical use of PET tracers have made possible the analysis of additional properties such as cellular metabolism and proliferative activity, using (18)F-FDG and (18)F-FLT. These tracers may lead to better quantification and targeting of different cell systems in the bone marrow. In this review the imaging of different bone marrow targets with radionuclides including PET tracers in various bone marrow diseases are discussed.

18F-FDG PET in squamous cell carcinoma of the oral cavity and oropharynx: a study on inter- and intraobserver agreement.

PURPOSE: Good observer agreement is mandatory for an effective imaging technique. However, little is known about the observer agreement of fluorine-18 fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) in head and neck squamous cell carcinoma. The aim of the present study was to evaluate the inter- and intraobserver agreement of interpretations of (18)F-FDG PET in head and neck SCC and to assess the influence of observer experience, tumor localizing, and tumor size on the agreement. PATIENTS AND METHODS: (18)F-FDG PET scans of 80 patients with oral and oropharyngeal SCC were reassessed twice by 2 experienced nuclear medicine physicians and 2 residents in nuclear medicine. The absolute agreement and Cohen's kappa were calculated by comparing the results of the 4 observers for the primary tumor, cervical metastases, and distant metastases/second primary tumor. To analyze the sensitivity and specificity, the results were compared with the findings from the histologic specimens or the follow-up data. RESULTS: The interobserver agreement of the nuclear medicine physicians revealed an absolute agreement and kappa of 0.91 and 0.58 for detecting the primary tumor, 0.94 and 0.83 for detecting cervical metastases, and 0.85 and 0.53 for detecting distant metastases/second primary tumors, respectively. The intraobserver agreement was greater overall than the interobserver agreement. Compared with the nuclear medicine physicians, the residents scored lower in interobserver agreement. The interobserver agreement decreased when localizing the malignancy more precisely. The agreement and sensitivity increased with tumor size. However, for small metastases, a high observer agreement was found owing to the nondetection of these malignancies. CONCLUSIONS: Good inter- and intraobserver agreement in SCC in the oral cavity or oropharynx with (18)F-FDG PET was found. Observer experience had limited influence on observer agreement. However, the agreement level decreased when a more precise anatomic tumor localization was required.

Somatostatin receptor scintigraphy might be useful for detecting skeleton abnormalities in patients with multiple myeloma and plasmacytoma.

PURPOSE: Somatostatin receptor expression has been demonstrated on a number of plasma cell lines. Therefore, we questioned whether somatostatin receptor scintigraphy (SRS) can be used to demonstrate in vivo multiple myeloma (MM) activity. METHODS: SRS was performed in newly diagnosed (n = 9) or relapsing (n = 18) MM patients or in patients with localized plasmacytoma (n = 2). The results were compared with radiographic findings. RESULTS: A positive SRS was demonstrated in 44% of the newly diagnosed patients, in 83% of the relapsed patients and in both patients with plasmacytoma. The SRS findings corresponded with radiographic abnormalities in 40% of the patients. However, in relapsed patients 60% demonstrated increased SRS uptake in areas without new radiographic abnormalities. The positive SRS corresponded with histologically proven disease activity and responded upon treatment. Moreover, immunohistochemical staining of MM material demonstrated concordant somatostatin receptor sst3 staining in five of six patients. CONCLUSION: These results demonstrate that SRS is a valuable tool to detect disease activity, especially in relapsing MM patients.

18F-FLT PET in hematologic disorders: a novel technique to analyze the bone marrow compartment.

UNLABELLED: Few diagnostic procedures are available to determine the degree of bone marrow cellularity and the numbers of cycling cells in patients with bone marrow disorders. Noninvasive imaging of the bone marrow compartment may be helpful. The PET tracer 3'-fluoro-3'-deoxy-L-thymidine (18F-FLT) has been developed recently. 18F-FLT uptake is related to the rate of DNA synthesis and increases with higher proliferation rates in many types of cancer. Background uptake of 18F-FLT in bone marrow is common. 18F-FLT PET might, therefore, visualize the high cycling activity of hematopoietic cells in the bone marrow compartment. Therefore, we investigated the feasibility of visualization and quantification of the activity of the bone marrow compartment with 18F-FLT PET to distinguish different hematologic disorders. METHODS: Clinical and laboratory data of 18 patients with myelodysplasia (MDS), chronic myeloproliferative disorders, myelofibrosis, aplastic anemia, or multiple myeloma were correlated with the results of 18F-FLT PET using visual analysis and the standardized uptake value (SUV). Findings were compared with those of healthy control subjects (n = 14). RESULTS: With SUV and visual analysis, a distinction could be made between MDS (n = 9), chronic myeloproliferative disorders (n = 3), and myelofibrosis (n = 3) compared with healthy control subjects. A significant increase in 18F-FLT uptake was observed in all of the studied patients with MDS and myeloproliferative disorders. In contrast, patients with myelofibrosis and aplastic anemia (n = 1) demonstrated a decline in bone marrow 18F-FLT uptake compared with healthy control subjects. Comparable results were observed in osteolytic lesions of patients with multiple myeloma (n = 2). CONCLUSION: 18F-FLT PET can be used to visualize the proliferative activity of the bone marrow compartment and may be helpful to distinguish separate hematologic disorders.

Nitrate administration increases blood flow in dysfunctional but viable myocardium, leading to improved assessment of myocardial viability: A PET study.

UNLABELLED: SPECT with 99mTc-labeled agents is better able to detect viability after nitrate administration. Nitrates induce vasodilation and may increase blood flow to severely hypoperfused but viable myocardium, thereby enhancing tracer delivery and improving the detection of viability. Quantitative data on the changes in blood flow are lacking in SPECT but can be provided by PET. The aim of the present study was to use PET to evaluate whether nitrate administration increases blood flow to chronically dysfunctional but viable myocardium. METHODS: 13N-Ammonia PET was used to quantitatively assess blood flow, and 18F-FDG PET was used as the gold standard to detect viable myocardium. Twenty-five patients with chronic ischemic left ventricular dysfunction underwent 13N-ammonia PET at rest and after nitrate administration. RESULTS: A significant increase in nitrate-enhanced blood flow was observed in viable segments (from 0.55 +/- 0.15 to 0.68 +/- 0.24 mL/min/g, P < 0.05). No statistically significant change in blood flow was observed in nonviable segments (0.60 +/- 0.20 vs. 0.55 +/- 0.18 mL/min/g). A ratio of at least 1.1 for nitrate-enhanced flow to resting flow allowed optimal detection of viable myocardium, yielding a sensitivity of 82% with a specificity of 100%. CONCLUSION: 13N-Ammonia PET showed a significant increase in nitrate-enhanced blood flow in viable myocardium, whereas blood flow remained unchanged after nitrate administration in nonviable myocardium. Nitrate use during myocardial perfusion imaging will lead to improved assessment of myocardial viability.