18F-FDG PET during stereotactic body radiotherapy for stage I lung tumours cannot predict outcome: a pilot study

(18)F-Fluorodeoxyglucose positron emission tomography (FDG PET) has been used to assess metabolic response several months after stereotactic body radiotherapy (SBRT) for early-stage non-small cell lung cancer. However, whether a metabolic response can be observed already during treatment and thus can be used to predict treatment outcome is undetermined. Ten medically inoperable patients with FDG PET-positive lung tumours were included. SBRT consisted of three fractions of 20 Gy delivered at the 80% isodose at days 1, 6 and 11. FDG PET was performed before, on day 6 immediately prior to administration of the second fraction of SBRT and 12 weeks after completion of SBRT. Tumour metabolism was assessed semi-quantitatively using the maximum standardized uptake value (SUV(max)) and SUV(70%). After the first fraction, median SUV(max) increased from 6.7 to 8.1 (p = 0.07) and median SUV(70%) increased from 5.7 to 7.1 (p = 0.05). At 12 weeks, both median SUV(max) and median SUV(70%) decreased by 63% to 3.1 (p = 0.008) and to 2.5 (p = 0.008), respectively. SUV increased during treatment, possibly due to radiation-induced inflammation. Therefore, it is unlikely that (18)F-FDG PET during SBRT will predict treatment success

FDG PET/CT in carcinoma of unknown primary

Carcinoma of unknown primary (CUP) is a heterogeneous group of metastatic malignancies in which a primary tumor could not be detected despite thorough diagnostic evaluation. Because of its high sensitivity for the detection of lesions, combined 18F-fluoro-2-deoxyglucose positron emission tomography (FDG PET)/computed tomography (CT) may be an excellent alternative to CT alone and conventional magnetic resonance imaging in detecting the unknown primary tumor. This article will review the use, diagnostic performance, and utility of FDG PET/CT in CUP and will discuss challenges and future considerations in the diagnostic management of CUP

Cell surface detection of vimentin, ACE2 and SARS-CoV-2 Spike proteins reveals selective colocalization at primary cilia

19 p.-9 fig.The SARS-CoV-2 Spike protein mediates docking of the virus onto cells prior to viral invasion. Several cellular receptors facilitate SARS-CoV-2 Spike docking at the cell surface, of which ACE2 plays a key role in many cell types. The intermediate filament protein vimentin has been reported to be present at the surface of certain cells and act as a co-receptor for several viruses; furthermore, its potential involvement in interactions with Spike proteins has been proposed. Nevertheless, the potential colocalization of vimentin with Spike and its receptors on the cell surface has not been explored. Here we have assessed the binding of Spike protein constructs to several cell types. Incubation of cells with tagged Spike S or Spike S1 subunit led to discrete dotted patterns at the cell surface, which consistently colocalized with endogenous ACE2, but sparsely with a lipid raft marker. Vimentin immunoreactivity mostly appeared as spots or patches unevenly distributed at the surface of diverse cell types. Of note, vimentin could also be detected in extracellular particles and in the cytoplasm underlying areas of compromised plasma membrane. Interestingly, although overall colocalization of vimentin-positive spots with ACE2 or Spike was moderate, a selective enrichment of the three proteins was detected at elongated structures, positive for acetylated tubulin and ARL13B. These structures, consistent with primary cilia, concentrated Spike binding at the top of the cells. Our results suggest that a vimentin-Spike interaction could occur at selective locations of the cell surface, including ciliated structures, which can act as platforms for SARS-CoV-2 docking.This work was supported by grants from Consejo Superior de Investigaciones Científicas, CSIC PTI Global Health (PIE 202020E223/CSIC-COV19-100), RTI2018-097624-B-I00 from Ministerio de Ciencia e Innovación, Micinn (Agencia Estatal de Investigación), Spain, and European Regional Development Fund, EDRF (. Á.V.P. and P.G.J. are the recipients of predoctoral contracts BES-2016-076965 and PRE2019-088194, respectively, from Ministerio de Ciencia e Innovación, Spain.Peer reviewe

Immunolocalization studies of vimentin and ACE2 on the surface of cells exposed to SARS-CoV-2 Spike proteins

The Spike protein from SARS-CoV-2 mediates docking of the virus onto cells and contributes to viral invasion. Several cellular receptors are involved in SARS-CoV-2 Spike docking at the cell surface, including ACE2 and neuropilin. The intermediate filament protein vimentin has been reported to be present at the surface of certain cells and act as a co-receptor for several viruses; furthermore, its potential involvement in interactions with Spike proteins has been proposed. Here we have explored the binding of Spike protein constructs to several cell types using low-temperature immunofluorescence approaches in live cells, to minimize internalization. Incubation of cells with tagged Spike S or Spike S1 subunit led to discrete dotted patterns at the cell surface, which showed scarce colocalization with a lipid raft marker, but consistent coincidence with ACE2. Under our conditions, vimentin immunoreactivity appeared as spots or patches unevenly distributed at the surface of diverse cell types. Remarkably, several observations including potential antibody internalization and adherence to cells of vimentin-positive structures present in the extracellular medium exposed the complexity of vimentin cell surface immunoreactivity, which requires careful assessment. Notably, overall colocalization of Spike and vimentin signals markedly varied with the cell type and the immunodetection sequence. In turn, vimentin-positive spots moderately colocalized with ACE2; however, a particular enrichment was detected at elongated structures positive for acetylated tubulin, consistent with primary cilia, which also showed Spike binding. Thus, these results suggest that vimentin-ACE2 interaction could occur at selective locations near the cell surface, including ciliated structures, which can act as platforms for SARS-CoV-2 docking.This work was supported by grants CSIC PTI Global Health (PIE 202020E223/CSIC-COV19-100), RTI2018-097624-B-I00 from Micinn (Agencia Estatal de Investigación), Spain and ERDF. Á.V.P. and P.G.J. are the recipients of predoctoral contracts BES-2016-076965 and PRE2019-088194, respectively, from Micinn, Spain.N

Review of imaging techniques for evaluating morphological and functional responses to the treatment of bone metastases in prostate and breast cancer.

Bone metastases are very common complications associated with certain types of cancers that frequently negatively impact the quality of life and functional status of patients; thus, early detection is necessary for the implementation of immediate therapeutic measures to reduce the risk of skeletal complications and improve survival and quality of life. There is no consensus or universal standard approach for the detection of bone metastases in cancer patients based on imaging. Endorsed by the Spanish Society of Medical Oncology (SEOM), the Spanish Society of Medical Radiology (SERAM), and the Spanish Society of Nuclear Medicine and Molecular Imaging (SEMNIM) a group of experts met to discuss and provide an up-to-date review of our current understanding of the biological mechanisms through which tumors spread to the bone and describe the imaging methods available to diagnose bone metastasis and monitor their response to oncological treatment, focusing on patients with breast and prostate cancer. According to current available data, the use of next-generation imaging techniques, including whole-body diffusion-weighted MRI, PET/CT, and PET/MRI with novel radiopharmaceuticals, is recommended instead of the classical combination of CT and bone scan in detection, staging and response assessment of bone metastases from prostate and breast cancer.Clinical trial registration: Not applicable