Clinical Indications of 11C-Choline PET/CT in Prostate Cancer Patients with Biochemical Relapse

Several studies investigated the potential role of imaging modalities in prostate cancer patients in case of biochemical recurrence. However, the role of molecular imaging has not been well established yet. Considering the results of the literature and of our own experience, we tried to summarize the potential applications of 11C-choline PET/CT in prostate cancer patients in case of biochemical relapse for the detection of lymph node and distant recurrence

Solitary Internal Mammary Lymph Node Metastases Detected by 18F-FDG-PET/CT in Ovarian Cancer

Internal mammary lymph nodes as solitary site of recurrent ovarian cancer have not been previously described. In this case report, 3 cases of late and very late isolated recurrence in internal mammary lymph nodes are presented. 18F-FDG-PET/CT allowed the diagnosis which was suspected by the increase of the serum CA-125 level in 2 out of 3 cases. Local treatment, consisting of surgery (in 2 patients) and radiation therapy (in 1 patient), permitted an optimal long-term disease control

CARE-compliant stereotactic radiotherapy of urothelial nodal metastases: A case report

The aim of the present study was to report the case of a 58-year-old male patient with ureteral carcinoma who underwent ureteroileostomy treatment. At 2 years following surgery, six lymph node metastases (LNMs) were detected in the patient's para-aortic and pelvic regions using F-18-labeled fluoro-2-deoxyglucose (FDG) positron emission tomography (PET)/CT. All LNMs were treated using stereotactic body radiotherapy (SBRT; 35-40 Gy/5 fractions). At 3 months after radiotherapy, F-18-FDG-PET/CT examination revealed a complete radiological and metabolic response of all targeted treatment sites in the patient. In the 2 years following radiotherapy, another three same-dose SBRT treatments were performed on single or multiple LNMs, which were all detected in the abdomen and pelvis of the patient. Overall, a total of 11 LNMs were targeted in the patient and all exhibited complete radiological and metabolic response following treatment. The only treatment side effect reported by the patient was a slight and temporary loss of appetite. In patients with lymph node oligometastases there are two options for radiotherapy: i) Irradiation focusing on LNMs alone; and ii) prophylactic irradiation of the entire lymph node area combined with a boost on macroscopic lesions. In the patient discussed in the present study, the choice of irradiation focusing on LNMs alone made it possible to postpone systemic therapies and instead use an optimally tolerated treatment. The treatment outcome in this patient indicated that there was no radioresistance of urothelial LNMs

First case of 18F-FACBC PET/CT-guided salvage radiotherapy for local relapse after radical prostatectomy with negative 11C-Choline PET/CT and multiparametric MRI: New imaging techniques may improve patient selection.

We present the first case of salvage radiotherapy based on the results of 18F-FACBC PET/CT performed for a PSA relapse after radical prostatectomy. The patients underwent 11CCholine PET/CT and multiparametric MRI that were negative while 18F-FACBC PET/CT visualized a suspected local relapse confirmed by transrectal ultrasound-guided biopsy. No distant relapse was detected. Thus the patient was submitted to salvage radiotherapy in the prostatic fossa. After 20 months of follow-up, the PSA was undetectable and 18F-FACBC PET/CT was negative. Salvage radiotherapy after surgery, provided that it is administered at the earliest evidence of the biochemical relapse, may improve cancer control and favourably influence the course of disease as well as the adjuvant approach. New imaging techniques may increase the efficacy of the salvage radiotherapy thus helping in the selection of the patients. Preliminary clinical reports showed an improvement in the detection rate of 20-40% of 18F-FACBC in comparison with 11C-Choline for the detection of disease relapse after radical prostatecomy, rendering the 18F-FACBC the potential radiotracer of the future for prostate cancer

11C-choline vs. 18F-FDG PET/CT in assessing bone involvement in patients with multiple myeloma

<p>Abstract</p> <p>Background</p> <p>Multiple Myeloma (MM) is a B cell neoplasm causing lytic or osteopenic bone abnormalities. Whole body skeletal survey (WBSS), Magnetic resonance (MR) and ¹⁸F-FDG PET/CT are imaging techniques routinely used for the evaluation of bone involvement in MM patients.</p> <p>Aim</p> <p>As MM bone lesions may present low ¹⁸F-FDG uptake; the aim of this study was to assess the possible added value and limitations of ¹¹C-Choline to that of ¹⁸F-FDG PET/CT in patients affected with MM.</p> <p>Methods</p> <p>Ten patients affected with MM underwent a standard ¹¹C-Choline PET/CT and an ¹⁸F-FDG PET/CT within one week. The results of the two scans were compared in terms of number, sites and SUV_maxof lesions.</p> <p>Results</p> <p>Four patients (40%) had a negative concordant ¹¹C-Choline and ¹⁸F-FDG PET/CT scans. Two patients (20%) had a positive ¹¹C-Choline and ¹⁸F-FDG PET/CT scans that identified the same number and sites of bone lesions. The remaining four patients (40%) had a positive ¹¹C-Choline and ¹⁸F-FDG PET/CT scan, but the two exams identified different number of lesions. Choline showed a mean SUV_maxof 5 while FDG showed a mean SUV_maxof 3.8 (P = 0.042). Overall, ¹¹C-Choline PET/CT scans detected 37 bone lesions and ¹⁸F-FDG PET/CT scans detected 22 bone lesions but the difference was not significant (P = 0.8).</p> <p>Conclusion</p> <p>According to these preliminary data, ¹¹C-Choline PET/CT appears to be more sensitive than ¹⁸F-FDG PET/CT for the detection of bony myelomatous lesions. If these data are confirmed in larger series of patients, ¹¹C-Choline may be considered a more appropriate functional imaging in association with MRI for MM bone staging.</p

Radiomic Features from Post-Operative 18F-FDG PET/CT and CT Imaging Associated with Locally Recurrent Rectal Cancer: Preliminary Findings

Locally Recurrent Rectal Cancer (LRRC) remains a major clinical concern, it rapidly invades pelvic organs and nerve roots, causing severe symptoms. Curative-intent salvage therapy offers the only potential for cure but it has a higher chance of success when LRRC is diagnosed at an early stage. Imaging diagnosis of LRRC is very challenging due to fibrosis and inflammatory pelvic tissue which can mislead even the most expert reader. This study exploited a radiomic analysis to enrich, through quantitative features, the characterization of tissue properties, thus favouring an accurate detection of LRRC by Computed Tomography (CT) and 18F-FDG-Positron Emission Tomography/CT (PET/CT). Of 563 eligible patients, undergoing radical resection (R0) of primary RC, 57 patients with suspected LRRC were included, 33 of which histologically confirmed. After manually segmenting suspected LRRC in CT and PET/CT, 144 radiomic features (RFs) were generated, and RFs were investigated for univariate significant discriminations (Wilcoxon rank-sum test, p&lt;0.050) of LRRC from NO LRRC. Five RFs in PET/CT (p&lt;0.017) and 2 in CT (p&lt;0.022) enabled, individually, a clear distinction of the groups, and one RF was shared by PET/CT and CT. Besides confirming the potential role of radiomics to advance LRRC diagnosis, the aforementioned shared RF describes LRRC as tissues having high local inhomogeneity due to evolving tissue’s properties

Anti-viral state segregates two molecular phenotypes of pancreatic adenocarcinoma: potential relevance for adenoviral gene therapy

<p>Abstract</p> <p>Background</p> <p>Pancreatic ductal adenocarcinoma (PDAC) remains a leading cause of cancer mortality for which novel gene therapy approaches relying on tumor-tropic adenoviruses are being tested.</p> <p>Methods</p> <p>We obtained the global transcriptional profiling of primary PDAC using RNA from eight xenografted primary PDAC, three primary PDAC bulk tissues, three chronic pancreatitis and three normal pancreatic tissues. The Affymetrix GeneChip HG-U133A was used. The results of the expression profiles were validated applying immunohistochemical and western blot analysis on a set of 34 primary PDAC and 10 established PDAC cell lines. Permissivity to viral vectors used for gene therapy, Adenovirus 5 and Adeno-Associated Viruses 5 and 6, was assessed on PDAC cell lines.</p> <p>Results</p> <p>The analysis of the expression profiles allowed the identification of two clearly distinguishable phenotypes according to the expression of interferon-stimulated genes. The two phenotypes could be readily recognized by immunohistochemical detection of the Myxovirus-resistance A protein, whose expression reflects the activation of interferon dependent pathways. The two molecular phenotypes discovered in primary carcinomas were also observed among established pancreatic adenocarcinoma cell lines, suggesting that these phenotypes are an intrinsic characteristic of cancer cells independent of their interaction with the host's microenvironment. The two pancreatic cancer phenotypes are characterized by different permissivity to viral vectors used for gene therapy, as cell lines expressing interferon stimulated genes resisted to Adenovirus 5 mediated lysis in vitro. Similar results were observed when cells were transduced with Adeno-Associated Viruses 5 and 6.</p> <p>Conclusion</p> <p>Our study identified two molecular phenotypes of pancreatic cancer, characterized by a differential expression of interferon-stimulated genes and easily recognized by the expression of the Myxovirus-resistance A protein. We suggest that the detection of these two phenotypes might help the selection of patients enrolled in virally-mediated gene therapy trials.</p

Raf Kinase Inhibitor Protein (RKIP) expression and function in human myometrium and leiomyoma

Many growth factors been identified in human myometrium and leiomyoma and activate multiple signaling pathways in order to regulate major cellular processes, including proliferation and fibrosis which are linked to uterine leiomyoma development and growth. The Raf kinase inhibitor protein (RKIP) has emerging roles as regulator of multiple signaling networks including mitogen activated protein (MAP) kinase cascade, as well as interaction with glycogen synthase kinase 3 (GSK3). In our study, we aimed to investigate the presence of RKIP in human myometrium and leiomyoma as well as to determine the effect of locostatin (RKIP inhibitor) on extracellular matrix (ECM) production, proliferation and migration in human myometrial and leiomyoma cells. Myometrial and leiomyoma tissues were used to investigate the localization and the expression level of RKIP through immunohistochemistry and western blotting. Myometrial and leiomyoma cells were treated with locostatin to measure ECM expression by real time PCR, GSK3b expression by western blotting, cell migration by wound-healing assay and cell proliferation by MTT assay. We found that RKIP is expressed in human myometrial and leiomyoma tissue. Locostatin treatment resulted in the activation of the MAPK signal pathway (ERK phosphorylation), providing a powerful validation of our targeting protocol. Further, RKIP inhibition by locostatin reduces ECM components. Moreover, the inhibition of RKIP by locostatin impaired cell proliferation and migration in both leiomyoma and myometrial cells. Finally, locostatin treatment reduced GSK3β expression. Therefore, even if the activation of MAPK pathway should increase proliferation and migration, the destabilization of GSK3β leads to the reduction of proliferation and migration of myometrial and leiomyoma cells

Analysis of tight junctions in placentas affected by chorioamnionitis: in vivo and in vitro analysis

The human placenta and fetal membranes provide a barrier regulating the transfer of materials between the mother and the developing fetus throughout gestation. Chorioamnionitis is an important risk factor for preterm delivery that is associated with high perinatal morbidity and mortality. Chorioamnionitis is the term applied to infections of the placenta and membranes resulting in high concentrations of IL- 1beta, IL-6, IL-8 and TGF-beta in the amniotic fluid (D’Alquen et al., 2005). With progression of inflammation, immune cells penetrate blood vessels and infiltrate the umbilical cord, resulting in funisitis (Romero and Mazor, 1988). In normal conditions the two important physical entities in endothelial/epithelial paracellular clefts are adherens junctions and tight junctions. Tight junction governs the paracellular movement of water, solutes and immune cells, through the intercellular space creating a boundary between the apical and basolateral sides of cellular barriers (Gruenheid and Finlay, 2003). We have evaluated the localization of tight junctions studying the Zonula Occludens-1 (ZO-1) and Occludin expressions as well as the localization of adherent junctions, testing the expression of VE-cadherin and beta-catenin in placentas from normal gestations, from preterm idiopathic deliveries and from chorioamnionitis by immunohistochemistry. In addition, we have evaluated the mRNAs by real time PCR, the protein levels of these molecules by Western blot analysis in placental tissues, and to better clarify the action of some cytokines on occludin we performed in vitro analysis of HUVEC cultures. Our more striking result is the decrease of occludin expression in placentas from chorioamnionitis and an evident action of the cytokines on this molecule

PSMA PET for the Evaluation of Liver Metastases in Castration-Resistant Prostate Cancer Patients: A Multicenter Retrospective Study

Simple Summary Visceral involvement in prostate cancer (PCa) represents a negative prognostic factor. Liver metastases typically occur in systemic, late-stage, castration-resistant prostate cancer (CRPC). The diagnostic performance of [68Ga]Ga-PSMA-11-PET for visceral metastases of CRPC patients has never been systematically assessed. Our aim was to evaluate the diagnostic performance of PSMA-PET compared to conventional imaging, i.e., CT or MRI, or liver biopsy in the detection of liver metastases in CRPC patients. The secondary aim was to assess the ability of radiomics to predict the presence of liver metastases. Regarding liver metastases assessment in CRPC patients, [68Ga]-PSMA-11-PET demonstrated moderate sensitivity while high specificity, positive predictive value, and reproducibility compared to conventional imaging and liver biopsy. However, nuclear medicine physicians should carefully assess the liver parenchyma on PET images, especially in patients at higher risk for liver metastases and with high PSA values. Moreover, radiomic features may aid in recognizing higher-risk patients to develop them. Background: To evaluate the diagnostic performance of PSMA-PET compared to conventional imaging/liver biopsy in the detection of liver metastases in CRPC patients. Moreover, we evaluated a PSMA-PET/CT-based radiomic model able to identify liver metastases. Methods: Multicenter retrospective study enrolling patients with the following inclusion criteria: (a) proven CRPC patients, (b) PSMA-PET and conventional imaging/liver biopsy performed in a 6 months timeframe, (c) no therapy changes between PSMA-PET and conventional imaging/liver biopsy. PSMA-PET sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for liver metastases were calculated. After the extraction of radiomic features, a prediction model for liver metastases identification was developed. Results: Sixty CRPC patients were enrolled. Within 6 months before or after PSMA-PET, conventional imaging and liver biopsy identified 24/60 (40%) patients with liver metastases. PSMA-PET sensitivity, specificity, PPV, NPV, and accuracy for liver metastases were 0.58, 0.92, 0.82, 0.77, and 0.78, respectively. Either number of liver metastases and the maximum lesion diameter were significantly associated with the presence of a positive PSMA-PET (p &lt; 0.05). On multivariate regression analysis, the radiomic feature-based model combining sphericity, and the moment of inverse difference (Idm), had an AUC of 0.807 (95% CI:0.686-0.920). Conclusion: For liver metastases assessment, [68Ga]Ga-PSMA-11-PET demonstrated moderate sensitivity while high specificity, PPV, and inter-reader agreement compared to conventional imaging/liver biopsy in CRPC patients