Nadia Withofs

18F-fluoride PET/CT for assessing bone involvement in prostate and breast cancers

ObjectiveTo evaluate the accuracy of 18F-fluoride PET/computed tomography (CT) to detect bone metastases (BMs) in a breast and prostate cancer population, using magnetic resonance imaging (MRI) or thin-slice CT as a gold standard. MethodsWe have prospectively included 34 patients with breast (N=24) or prostate cancer (N=10) at high risk of BMs. Whole-body PET/CT (low-dose CT) and bone scintigraphy (BS) with single photon emission CT were obtained for all 34 patients and the results compared with a radiological gold standard. ResultsOut of the 386 foci detected by PET/CT, 219 (56.7%) could be verified by CT or MRI. Eighty-six additional foci were detected by BS (n=46) or seen only by CT (n=9), MRI (n=23), or both CT and MRI (n=8). The total number of verified lesions was therefore 274 (58.1%), including 119 (43.4%) benign and 155 (56.6%) BM. The sensitivity, specificity, and accuracy of 18F-fluoride PET/CT were 76, 84.2, and 80%, respectively. For BS, they were 44.8, 79.2, and 60%, respectively. Sensitivity significantly decreased for the lytic lesions. The accuracy of PET/CT was significantly superior to BS for pelvic and lumbar lesions. PET/CT provided a correct diagnosis (M+/M0) in 32 of 33 patients (one false positive) compared with 28 of 33 with BS (four false positive, one false positive). Conclusion 18F-fluoride PET/CT is significantly more accurate than BS for detecting BMs from breast and prostate cancers.

Twist1 Suppresses Senescence Programs and Thereby Accelerates and Maintains Mutant Kras-Induced Lung Tumorigenesis

KRAS mutant lung cancers are generally refractory to chemotherapy as well targeted agents. To date, the identification of drugs to therapeutically inhibit K-RAS have been unsuccessful, suggesting that other approaches are required. We demonstrate in both a novel transgenic mutant Kras lung cancer mouse model and in human lung tumors that the inhibition of Twist1 restores a senescence program inducing the loss of a neoplastic phenotype. The Twist1 gene encodes for a transcription factor that is essential during embryogenesis. Twist1 has been suggested to play an important role during tumor progression. However, there is no in vivo evidence that Twist1 plays a role in autochthonous tumorigenesis. Through two novel transgenic mouse models, we show that Twist1 cooperates with KrasG12D to markedly accelerate lung tumorigenesis by abrogating cellular senescence programs and promoting the progression from benign adenomas to adenocarcinomas. Moreover, the suppression of Twist1 to physiological levels is sufficient to cause Kras mutant lung tumors to undergo senescence and lose their neoplastic features. Finally, we analyzed more than 500 human tumors to demonstrate that TWIST1 is frequently overexpressed in primary human lung tumors. The suppression of TWIST1 in human lung cancer cells also induced cellular senescence. Hence, TWIST1 is a critical regulator of cellular senescence programs, and the suppression of TWIST1 in human tumors may be an effective example of pro-senescence therapy.

PET/CT of Skull Base Meningiomas Using 2-18F-Fluoro-l-Tyrosine: Initial Report

Precise delineation of the shape of skull base meningiomas is critical for their treatment and follow-up but is often difficult using conventional imaging such as CT and MRI. We report our results with PET/CT and 2-18F-fluoro-l-tyrosine (18F-TYR), a marker of amino acid transport, as part of the yearly follow-up of irradiated patients. Methods: Eleven patients (mean age, 56.5 y) with skull base meningiomas (n = 13 lesions) previously irradiated were included. All patients received 300 MBq of 18F-TYR and were imaged after 30 min of uptake, using a dedicated PET/CT system. The images were first visually examined, and regions of interest (ROI) were then placed over the transaxial PET slice showing the highest uptake. Another ROI was placed over the normal parietal cortex. Tumor-to-cortex activity ratios were obtained by dividing the maximum pixel value in the tumor ROI by the maximum pixel value in the cortex ROI. The PET/CT images were compared with the MR images obtained as part of routine follow-up. Results: Accumulation of the tracer was higher in all meningiomas than in the surrounding tissue. The tumor-to-cortex activity ratio was 2.53 ± 0.35 (range, 1.3–6). Nonneoplastic tissue such as hyperemic cavernous sinus did not take up the radionuclide and was therefore easily distinguished from the meningioma. The 18F-TYR anomalies completely overlapped with the MR image in 54% of the tumors, extended beyond the MRI lesion in 38% of the tumors, and were smaller in 8% of the tumors. Conclusion: Meningiomas of the skull base are clearly visualized using 18F-TYR PET/CT, even after irradiation. In addition to MRI, 18F-TYR PET/CT images may contribute to the evaluation, delineation, and follow-up of these tumors.

The role of positron emission tomography-computed tomography and magnetic resonance imaging in diagnosis and follow-up of multiple myeloma

Multiple myeloma is the second most common hematologic malignancy and occurs most commonly in elderly patients. Almost all multiple myeloma patients develop bone lesions in the course of their disease or have evidence of bone loss at initial diagnosis. Whole-body conventional radiography remains the gold standard in the diagnostic evaluation, but computed tomography, magnetic resonance imaging and 18F-fluorodeoxyglucose positron emission tomography are increasingly used as complementary techniques in the detection of bone lesions. Moreover, the number of lesions detected and the presence of extramedullary disease give strong prognostic information. These new techniques may help to assess treatment response in solitary plasmacytoma or in multiple myeloma. In this article, we review recent data on the different imaging techniques used at diagnosis and in the assessment of treatment response, and discuss some current issues.

18F-FPRGD2 PET/CT Imaging of Integrin αvβ3 in Renal Carcinomas: Correlation with Histopathology

This study aimed to correlate 18F-FB-mini-PEG-E[c(RGDyK)](2) (18F-FPRGD2) uptake to integrin αvβ3 expression and angiogenesis in renal tumors. Methods: 18F-FPRGD2 PET/CT was performed on 27 patients before surgical resection (median 4 d) of a renal mass. The 18F-FPRGD2 uptake was compared with integrin αvβ3, CD31, CD105, and Ki-67 using immunohistochemistry; with placental growth factor and vascular endothelial growth factor receptors 1 and 2 using reverse transcription polymerase chain reaction; and with vascular endothelial growth factor A isoforms using enzyme-linked immunosorbent assay. Results: Overall, 18F-FPRGD2 uptake significantly correlated (P < 0.0001) with integrin αvβ3 expression in renal masses. However, it correlated only with integrin αvβ3-positive vessels in the group of papillary carcinomas whereas it correlated with integrin αvβ3 expression by tumor cells in the clear cell carcinoma group. Conclusion: 18F-FPRGD2 uptake reflects the expression of integrin αvβ3 in renal tumors but represents angiogenesis only when tumor cells do not express the integrin.

Contribution of positron emission tomography in pleural disease.

INTRODUCTION Positron emission tomography (PET) now plays a clear role in oncology, especially in chest tumours. We discuss the value of metabolic imaging in characterising pleural pathology in the light of our own experience and review the literature. BACKGROUND PET is particularly useful in characterising malignant pleural pathologies and is a factor of prognosis in mesothelioma. Metabolic imaging also provides clinical information for staging lung cancer, in researching the primary tumour in metastatic pleurisy and in monitoring chronic or recurrent pleural pathologies. CONCLUSIONS PET should therefore be considered as a useful tool in the diagnosis of liquid or solid pleural pathologies.

FDG PET/CT for rectal carcinoma radiotherapy treatment planning: comparison of functional volume delineation algorithms and clinical challenges.

PET/CT imaging could improve delineation of rectal carcinoma gross tumor volume (GTV) and reduce interobserver variability. The objective of this work was to compare various functional volume delineation algorithms. We enrolled 31 consecutive patients with locally advanced rectal carcinoma. The FDG PET/CT and the high dose CT (CTRT) were performed in the radiation treatment position. For each patient, the anatomical GTVRT was delineated based on the CTRT and compared to six different functional/metabolic GTVPET derived from two automatic segmentation approaches (FLAB and a gradient‐based method); a relative threshold (45% of the SUVmax) and an absolute threshold (SUV>2.5), using two different commercially available software (Philips EBW4 and Segami OASIS). The spatial sizes and shapes of all volumes were compared using the conformity index (CI). All the delineated metabolic tumor volumes (MTVs) were significantly different. The MTVs were as follows (mean±SD):GTVRT(40.6±31.28ml); FLAB(21.36±16.34ml); the gradient‐based method (18.97±16.83ml); OASIS45%(15.89±12.68ml); Philips45%(14.52±10.91ml); OASIS2.5(41.62±33.26ml); Philips2.5(40±31.27ml). CI between these various volumes ranged from 0.40 to 0.90. The mean CI between the different MTVs and the GTVCT was <0.4. Finally, the DICOM transfer of MTVs led to additional volume variations. In conclusion, we observed large and statistically significant variations in tumor volume delineation according to the segmentation algorithms and the software products. The manipulation of PET/CT images and MTVs, such as the DICOM transfer to the Radiation Oncology Department, induced additional volume variations. PACS number: 87.55.D‐

Apport de l'imagerie par tomographie a emission de positons dans la pathologie pleurale. Interet de la TEP en pathologie pleurale.

Introduction La tomographie par emission de positons (TEP) s’est clairement positionnee en oncologie, en particulier thoracique. A la lueur de notre experience et de la revue de la litterature, nous precisons l’interet de l’imagerie metabolique dans l’approche diagnostique de la pathologie pleurale. Etat des connaissances La TEP permet en particulier la caracterisation d’une pleuropathie maligne, et constitue un facteur pronostique du mesotheliome. L’imagerie metabolique apporte des informations cliniques pour le bilan d’extension d’un cancer pulmonaire, pour la recherche de la tumeur primitive d’une pleuresie metastatique, ainsi que pour le suivi d’une pathologie pleurale chronique ou recurrente. Conclusions Il est, des lors, justifie que la TEP integre l’arsenal diagnostique d’une pathologie pleurale tant liquidienne que solide.

Molecular mechanisms, current management and next generation therapy in myeloma bone disease.

Abstract Multiple myeloma (MM) bone disease is a major cause of morbidity and mortality in MM patients and persists even in patients in remission. This bone disease is caused by an uncoupling of bone remodeling, with increased osteoclast and decreased osteoblast activity and formation, culminating in lytic bone destruction. Bisphosphonates are the current standard of care but new therapies are needed. As the molecular mechanisms controlling MM bone disease are increasingly well understood, new therapeutic targets are extensively explored in the preclinical setting and initial clinical trials with novel compounds now show promising results. In this review, we will provide a comprehensive overview of the biology of MM bone disease, summarize its current clinical management and discuss preclinical and clinical data on next generation therapies.

Acute intramural haematoma of the ascending aorta

A 77-year-old man with a history of mantle cell lymphoma underwent a FDG PET/CT to explore fever and chest pain. A diffuse high FDG uptake is seen within the wall of the enlarged ascending aorta extending from the aortic valve to the brachiocephalic, right subclavian and left common carotid arteries. A photopenic area in the ascending aorta, best seen on the coronal view, suggests the presence of an intramural haematoma. The study is thus consistent with the diagnosis of acute intramural haematoma of the ascending aorta, which was confirmed by echo Doppler, angio-CT and histological examination. Acute intramural haematoma is considered as a variant of aortic dissection. It can evolve to stabilization and resolution or progress towards classical aortic dissection, development of ulcer-like projections of the aorta, and formation of an aortic aneurysm. Because of this unpredictable evolution, guidelines for its treatment are not clear [1]. Increased FDG uptake by acute intramural haematoma has been reported [2, 3], but it is not known whether such increased uptake is associated with a higher risk of rupture and progression, as shown by PET studies in type-B aortic dissection [4].