Clinical PET Imaging in Prostate Cancer.

Prostate cancer is the second most common cancer in men worldwide, with a wide spectrum of biologic behavior ranging from indolent low-risk disease to highly aggressive castration-resistant prostate cancer. Conventional imaging with computed tomography, magnetic resonance imaging, and bone scintigraphy is limited for the detection of nodal disease and distant bone metastases. In addition, advances in the available therapeutic options, both localized and systemic, drive the requirement for precise diagnostic and prognostic tools to refine the individual therapeutic approach at various times in the management of patients with prostate cancer. Positron emission tomography (PET) has a rapidly evolving role in the assessment of prostate cancer, particularly in the scenario of biochemical relapse. Fluorine 18 (18F) fluorodeoxyglucose, the most widely available PET tracer, has limitations, particularly in indolent prostate cancer. In the past decade, several PET tracers with specific molecular targets have reached the clinical domain. These tracers include 18F-sodium fluoride, which is a bone-specific biomarker of osteoblastic activity; 18F-choline and carbon 11-choline, which are directed at cell membrane metabolism; gallium 68-prostate-specific membrane antigen ligands; and, more recently, an amino acid analog, 18F-fluciclovine (anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid; also known as FACBC), which is also directed at cell membrane turnover. The mechanisms of actions of the clinically available PET tracers are reviewed, as well as their role in the imaging of prostate cancer with reference to relevant guidelines and the technical and imaging pearls and pitfalls of these tracers. ©RSNA, 2017.

Expression of human tissue factor pathway inhibitor on vascular smooth muscle cells inhibits secretion of macrophage migration inhibitory factor and attenuates atherosclerosis in ApoE-/- mice.

BACKGROUND: Tissue factor (TF) and coagulation proteases are involved in promoting atherosclerosis, but the molecular and cellular bases for their involvement are unknown. METHODS AND RESULTS: We generated a new strain (ApX4) of apolipoprotein E-deficient mice expressing a membrane-tethered human tissue factor pathway inhibitor fusion protein on smooth muscle actin-positive cells, including vascular smooth muscle cells (SMCs). ApX4 mice developed little atherosclerosis on either a normal chow or high-fat diet. Lipid levels were similar to those in parental ApoE(-/-) mice, and there was no detectable difference in systemic (circulating) tissue factor pathway inhibitor levels or activity. The small lipid-rich lesions that developed had markedly reduced leukocyte infiltrates, and in contrast to ApoE(-/-) mice, SMCs did not express macrophage migratory inhibitory factor (MIF), including at sites distant from atheromatous lesions. Low levels of circulating MIF in ApX4 mice normalized to levels seen in ApoE(-/-) mice after injection of an inhibitory anti-human tissue factor pathway inhibitor antibody, which also led to MIF expression by tissue factor-positive medial SMCs. MIF production by SMCs in ApoE(-/-) mice in vitro and in vivo was shown to be dependent on tissue factor and protease-activated receptor signaling, which were inhibited in ApX4 mice. CONCLUSIONS: Our data indicate that tissue factor plays a hitherto unreported role in the generation of MIF by SMCs in atherosclerosis-prone ApoE(-/-) mice, inhibition of which significantly prevents the development of atherosclerosis, through inhibition of leukocyte recruitment. These data significantly enhance our understanding of the pathophysiology of this important pathology and suggest new potential translational strategies to prevent atheroma formation.

The role of routine clinical pretreatment 18F-FDG PET/CT in predicting outcome of colorectal liver metastasis.

OBJECTIVE: The aim of this study was to determine the value of SUV-based metabolic parameters derived from pretreatment F-FDG PET/CT of colorectal liver metastases in predicting disease response, progression-free survival (PFS), and overall survival (OS). PATIENTS AND METHODS: We retrospectively reviewed 70 colorectal patients with liver metastases who underwent pretreatment F-FDG PET/CT. SUVmean, SUVmax, TLG (total lesion glycolysis), metabolic tumor volume, and metabolic tumor diameter were the metabolic parameters derived from volume of interest analysis of the most FDG-avid liver lesion in each subject. Clinical and laboratory parameters were recorded. Tumor response was assessed by response evaluation criteria in solid tumors 1.1 criteria at 12 weeks after treatment. Associations between tumor response, metabolic parameters, and clinical/laboratory parameters were examined by 1-way analysis of variance. The relationship of the metabolic parameters with PFS and OS was determined by Kaplan-Meier analyses and further confirmed with multivariate Cox regression analyses. RESULTS: SUVmean less than 4.48, SUVmax less than 6.59, TLG less than 75.2, metabolic tumor volume less than 4.49 cm, and hemoglobin level greater than or equal to 11 g/dL were associated with longer PFS (P < 0.05). Prior surgery or radiofrequency ablation to the liver metastases was the only additional factor shown to be associated with longer OS. CONCLUSIONS: SUV-based metabolic parameters derived from pretreatment F-FDG PET/CT can predict PFS in colorectal liver metastases.

Frequency and significance of physiological versus pathological uptake of 68Ga-DOTATATE in the pancreas: validation with morphological imaging.

AIM: The objective of this study was to assess the relevance of physiological (68)Ga-DOTATATE PET/CT findings in the pancreas guided by morphological imaging (MI) in comparison with pathological tumour uptake in patients with neuroendocrine tumours (NETs). METHODS: A total of 138 patients with pancreatic NET (pNET; n=38) or non-pNET (n=100) underwent (68)Ga-DOTATATE PET/CT. Pancreatic regions with intensity higher than background were localized with anatomical reference support [head/uncinate process (HUP); body/tail (BT)] and classified as tumour, suspicious or physiological. Maximum standardized uptake value (SUV(max)) was assessed in all regions. PET/CT findings were compared with MI results. RESULTS: Physiological uptake was seen in 10/38 pNETs (SUV(max) range, mean±SD and median in HUP and BT: 2.4-12.7, 5.9±3.2 and 4.6; 3.8-6.6, 6.6±2.5 and 5.6, respectively). A total of 18/38 showed high uptake (SUV(max) range, mean±SD and median in HUP and BT: 6.9-50, 26.9±13.5 and 27; 10-151, 32.2±36 and 19.4, respectively) with abnormal MI results. Among 10/38 patients we observed a total of n=15 discordant findings between PET/CT and MI: two lesions detected by MI did not correspond to any pathologial uptake on PET/CT, five suspicious uptake in the HUP did not correspond to any abnormal finding on MI, one HUP suspicious uptake correspondend to a lymphadenopaty on MI and seven suspicious BT uptake correspondend to calcification (1/6), cystic lesions (3/6), lesion different form the one detected by PET/CT (1/6) or negative findings (2/6) on MI. Among the 100 patients with non-pNETs, 97 showed homogeneous uptake and three had suspicious pancreatic uptake without concordant findings on MI. CONCLUSION: Physiological pancreatic uptake of (68)Ga-DOTATATE showed low SUV(max), whereas tumours showed higher SUV(max); this is in agreement with previously published data. Equivocal findings showed SUV(max) in the grey area between physiological and pathological ranges, and for these lesions MI and histological confirmation are required for final diagnosis.

Human umbilical cord blood-derived mesenchymal stem cells do not differentiate into neural cell types or integrate into the retina after intravitreal grafting in neonatal rats.

This study investigated the ability of mesenchymal stem cells (MSCs) derived from full-term human umbilical cord blood to survive, integrate and differentiate after intravitreal grafting to the degenerating neonatal rat retina following intracranial optic tract lesion. MSCs survived for 1 week in the absence of immunosuppression. When host animals were treated with cyclosporin A and dexamethasone to suppress inflammatory and immune responses, donor cells survived for at least 3 weeks, and were able to spread and cover the entire vitreal surface of the host retina. However, MSCs did not significantly integrate into or migrate through the retina. They also maintained their human antigenicity, and no indication of neural differentiation was observed in retinas where retinal ganglion cells either underwent severe degeneration or were lost. These results have provided the first in vivo evidence that MSCs derived from human umbilical cord blood can survive for a significant period of time when the host rat response is suppressed even for a short period. These results, together with the observation of a lack of neuronal differentiation and integration of MSCs after intravitreal grafting, has raised an important question as to the potential use of MSCs for neural repair through the replacement of lost neurons in the mammalian retina and central nervous system.