Comparing the Differential Diagnostic Values of 18F-Alfatide II PET/CT between Tuberculosis and Lung Cancer Patients.

Purpose: To compare the differential diagnostic values of 18F-Alfatide II PET/CT between tuberculosis and lung cancer patients and in patients with sarcoidosis and common inflammation. Methods: Nine inflammation patients (4 tuberculosis, 3 sarcoidosis, and 2 common inflammation) and 11 lung cancer patients were included in this study. All patients underwent 18F-FDG and 18F-Alfatide II PET/CT within 2 weeks, followed by biopsy and surgery. The maximized standard uptake value (SUVmax) and the mean standard uptake value (SUVmean) were evaluated. Results: The active tuberculosis lesions showed a high accumulation of 18F-FDG, but varying degrees of accumulation of 18F-Alfatide II, including negative results. The SUVmax of 18F-Alfatide II in malignant lesions was significantly higher than that in tuberculosis (4.08 ± 1.51 versus 2.63 ± 1.34, P = 0.0078). Three patients with sarcoidosis showed negative results in 18F-Alfatide II PET/CT. Conclusions: The expression of αVß3 is much lower in tuberculosis as compared to that in lung cancer, and accumulation of 18F-Alfatide II varied even in lesions of the same patient. The negative results of sarcoidosis patients led to the speculation that αVß3 was not expressed in those lesions.

Non-invasive glucagon-like peptide-1 receptor imaging in pancreas with (18)F-Al labeled Cys(39)-exendin-4.

PURPOSE: Glucagon-like peptide-1 receptor (GLP-1R) is abundantly expressed on beta cells and may be an ideal target for the pancreas imaging. Monitoring the GLP-1R of pancreas could be benefit for understanding the pathophysiology of diabetes. In the present study, (18)F-Al labeled exendin-4 analog, (18)F-Al-NOTA-MAL-Cys(39)-exendin-4, was evaluated for PET imaging GLP-1R in the pancreas. METHODS: The targeting of (18)F-Al labeled exendin-4 analog was examined in healthy and streptozotocin induced diabetic rats. Rats were injected with (18)F-Al-NOTA-MAL-Cys(39)-exendin-4 and microPET imaging was performed at 1 h postinjection, followed by ex vivo biodistribution. GLP-1R expression in pancreas was determined through post mortern examinations. RESULTS: The pancreas of healthy rats was readily visualized after administration of (18)F-Al-NOTA-MAL-Cys(39)-exendin-4, whereas the pancreas of diabetic rats, as well as those from rats co-injected with excess of unlabeled peptides, was barely visible by microPET. At 60 min postinjection, the pancreatic uptakes were 1.02 ± 0.15%ID/g and 0.23 ± 0.05%ID/g in healthy and diabetic rats respectively. Under block, the pancreatic uptakes of non-diabetic rats reduced to 0.21 ± 0.07%ID/g at the same time point. Biodistribution data and IHC staining confirmed the findings of the microPET imaging. CONCLUSION: The favorable preclinical data indicated that (18)F-Al-NOTA-MAL-Cys(39)-exendin-4may be suitable for non-invasive monitoring functional pancreatic beta cells.

(18)F-Alfatide II PET/CT in healthy human volunteers and patients with brain metastases.

PURPOSE: We report the biodistribution and radiation dosimetry of an integrin αvß3 specific PET tracer (18)F-AlF-NOTA-E[PEG4-c(RGDfk)]2) (denoted as (18)F-Alfatide II). We also assessed the value of (18)F-Alfatide II in patients with brain metastases. METHODS: A series of torso (from the skull to the thigh) static images were acquired in five healthy volunteers (3 M, 2 F) at 5, 10, 15, 30, 45, and 60 min after injection of (18)F-Alfatide II (257 ± 48 MBq). Regions of interest (ROIs) were drawn manually, and the time-activity curves (TACs) were obtained for major organs. Nine patients with brain metastases were examined by static PET imaging with (18)F-FDG (5.55 MBq/kg) and (18)F-Alfatide II. RESULTS: Injection of (18)F-Alfatide II was well tolerated in all healthy volunteers, with no serious tracer-related adverse events found. (18)F-Alfatide II showed rapid clearance from the blood pool and kidneys. The total effective dose equivalent (EDE) and effective dose (ED) were 0.0277 ± 0.003 mSv/MBq and 0.0198 ± 0.002 mSv/MBq, respectively. The organs with the highest absorbed dose were the kidneys and the spleen. Nine patients with 20 brain metastatic lesions identified by MRI and/or CT were enrolled in this study. All 20 brain lesions were visualized by (18)F-Alfatide II PET, while only ten lesions were visualized by (18)F-FDG, and 13 by CT. CONCLUSION: F-Alfatide II is a safe PET tracer with a favorable dosimetry profile. The observed ED suggests that (18)F-Alfatide II is feasible for human studies. (18)F-Alfatide II has potential value in finding brain metastases of different cancers as a biomarker of angiogenesis.

Pilot Prospective Evaluation of (18)F-Alfatide II for Detection of Skeletal Metastases.

This pilot prospective evaluation study is to verify the efficiency of (18)F-Alfatide II, a specific PET imaging agent for integrin αvß3, in detecting bone metastasis in human, with comparison to (18)F-FDG PET. Thirty recruited patients underwent (18)F-FDG and (18)F-alfatide II PET/CT successively within days. The final diagnosis of bone lesions was established based on the comprehensive assessment of all available data and clinical follow-up, which fall into four groups: osteolytic, osteoblastic, mixed and bone marrow. Visual analysis and quantification of SUVmax were performed to compare the detection sensitivity of (18)F-Alfatide II and (18)F-FDG PET. Eleven patients were found to have a total of 126 bone metastasis lesions. (18)F-Alfatide II PET can detect the bone metastatic lesions with good contrast and higher sensitivity (positive rate of 92%) than (18)F-FDG PET (77%). Especially, (18)F-Alfatide II PET showed superiority to (18)F-FDG PET in detecting osteoblastic (70% vs. 53%) and bone marrow metastatic lesions (98% vs. 77%). In conclusion, (18)F-Alfatide II PET/CT can be used to detect skeletal and bone marrow metastases, with nearly 100% sensitivity in osteolytic, mixed and bone marrow lesions. The sensitivity of (18)F-Alfatide II PET/CT in osteoblastic metastases is relatively low but still significantly higher than that of (18)F-FDG PET/CT. This pilot clinical study warrants the further application of (18)F-Alfatide II PET/CT in metastatic lesion detection, patient management and drug therapy response monitoring.

Carcinosarcoma of the uterine corpus on 18F-FDG PET/CT in a postmenopausal woman with elevated AFP.

Uterine carcinosarcoma (termed malignant mixed müllerian tumor) is a rare neoplasm of the uterus with a poor prognosis. There have been very few cases in the literature describing the PET/CT findings of uterine carcinosarcoma. We report a case of tissue-proven carcinosarcoma of the uterine corpus in a 65-year-old woman with elevated serum alpha-fetoprotein (AFP), whose 18F-FDG PET/CT showed a 10.3-cm mass in the uterus with uneven high FDG uptake. The SUVmax was 12.8. After surgery, the patient received 6 courses of chemotherapy, and the serum levels of AFP decreased to reference range.

First experience of 18F-alfatide in lung cancer patients using a new lyophilized kit for rapid radiofluorination.

UNLABELLED: (18)F-FPPRGD2, which was approved for clinical study recently, has favorable properties for integrin targeting and showed potential for antiangiogenic therapy and early response monitoring. However, the time-consuming multiple-step synthesis may limit its widespread applications in the clinic. In this study, we developed a simple lyophilized kit for labeling PRGD2 peptide ((18)F-AlF-NOTA-PRGD2, denoted as (18)F-alfatide) using a fluoride-aluminum complex that significantly simplified the labeling procedure. METHODS: Nine patients with a primary diagnosis of lung cancer were examined by both static and dynamic PET imaging with (18)F-alfatide, and 1 tuberculosis patient was investigated using both (18)F-alfatide and (18)F-FDG imaging. Standardized uptake values were measured in tumors and other main organs at 30 min and 1 h after injection. Kinetic parameters were calculated by Logan graphical analysis. Immunohistochemistry and staining intensity quantification were performed to confirm the expression of integrin α(v)ß(3). RESULTS: Under the optimal conditions, the whole radiosynthesis including purification was accomplished within 20 min with a decay-corrected yield of 42.1% ± 2.0% and radiochemical purity of more than 95%. (18)F-alfatide PET imaging identified all tumors, with mean standardized uptake values of 2.90 ± 0.10. Tumor-to-muscle and tumor-to-blood ratios were 5.87 ± 2.02 and 2.71 ± 0.92, respectively. CONCLUSION: (18)F-alfatide can be produced with excellent radiochemical yield and purity via a simple, 1-step, lyophilized kit. PET scanning with (18)F-alfatide allows specific imaging of αvß3 expression with good contrast in lung cancer patients. This technique might be used for the assessment of angiogenesis and for planning and response evaluation of cancer therapies that would affect angiogenesis status and integrin expression levels.

[The value of extra-lung lesions on ¹8F-FDG PET/CT in improving diagnosis of lung cancer].

BACKGROUND AND OBJECTIVE: ¹8F-FDG PET/CT has several shortcomings in discriminating between lung carcinoma and pulmonary benign lesions. The aims of the present study is to explore the value of extra-lung lesions on ¹8F-FDG PET/CT image in the diagnosis of lung cancer. METHODS: A total of 126 suspected lung cancer patients underwent ¹8F-FDG PET/CT scan. Preliminary diagnoses were based on the PET characteristics, SUVmean value, and CT characteristics of the lesions in the lung, and the diagnoses were modified based on the detected extra-lung lesions. The difference between the two methods and their disparity were calculated. RESULTS: Extra-lung lesions were identified on the PET/CT image in 81 patients; extra-lung metastasis modified 13 probable malignancies to affirmative malignancy and 1 probable malignancy to benign lesion. Non-metastasis modified 2 probable malignancies to affirmative malignancy and 1 probable malignancy to benign lesion. Fifteen were correct, whereas 2 were misdiagnosed. The diagnoses modification rate was 13.5% (17/126), and the modified diagnoses accuracy is 88.2% (15/17). CONCLUSIONS: Extra-lung lesions demonstrated on ¹8F-FDG PET/CT improved the diagnostic accuracy of lung cancer. Tuberculosis was identified as the most important reason for false positive diagnoses after modification by extra-lung lesions.

Evaluation of the relationship between [18F]FDG and P-glycoprotein expression: an experimental study.

INTRODUCTION: P-glycoprotein (P-gp) is a cell-membrane-associated protein that transports a variety of drug substrates. We sought to evaluate the relationship between 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) and P-gp expression using breast carcinoma Bcap37/multidrug resistant (MDR1) and Bcap37 in vitro and in vivo. METHODS: The function of P-gp expressed in Bcap37/MDR1 cells was evaluated using verapamil (VER), a classical inhibitor of P-gp. The accumulation of 99mTc-methoxyisobutylisonitrile ([99mTc]MIBI) in vitro was measured. In vivo imaging of severe combined immune deficiency (SCID) mice implanted with Bcap37 and Bcap37/MDR1 cells was performed by scintigraphy and micro-positron emission tomography (PET). RESULTS: The uptake of [99mTc]MIBI was 0.62%±0.05% in the Bcap37/MDR1 cells and 2.02%±0.28% in the Bcap37 cells. VER significantly increased the uptake of [99mTc]MIBI in the Bcap37/MDR1 cells (1.90%±0.09%) but not in the Bcap37 cells (2.15%±0.27%). In vivo, neither the Bcap37 nor Bcap37/MDR1 tumors grown in the SCID mice could be detected by [99mTc]MIBI scintigraphy. Both the Bcap37 and Bcap37/MDR1 tumors were visible by micro-PET. The mean standardized uptake value (SUV) was significantly higher in the Bcap37 tumors (1.00±0.06) than in the Bcap37/MDR1 (0.67±0.11) tumors. VER significantly increased the mean SUV in the Bcap37/MDR1 tumors (1.02±0.16) but not in the Bcap37 tumors (1.09±0.22). CONCLUSIONS: [18F]FDG combined with VER may be an effective noninvasive method of determining P-gp expression in tumors.