Thoracic positron emission tomography: 18F-fluorodeoxyglucose and beyond.

Ongoing technologic and therapeutic advancements in medicine are now testing the limits of conventional anatomic imaging techniques. The ability to image physiology, rather than simply anatomy, is critical in the management of multiple disease processes, especially in oncology. Nuclear medicine has assumed a leading role in detecting, diagnosing, staging and assessing treatment response of various pathologic entities, and appears well positioned to do so into the future. When combined with computed tomography (CT) or magnetic resonance imaging (MRI), positron emission tomography (PET) has become the sine quo non technique of evaluating most solid tumors especially in the thorax. PET/CT serves as a key imaging modality in the initial evaluation of pulmonary nodules, often obviating the need for more invasive testing. PET/CT is essential to staging and restaging in bronchogenic carcinoma and offers key physiologic information with regard to treatment response. A more recent development, PET/MRI, shows promise in several specific lung cancer applications as well. Additional recent advancements in the field have allowed PET to expand beyond imaging with 18F-flurodeoxyglucose (FDG) alone, now with the ability to specifically image certain types of cell surface receptors. In the thorax this predominantly includes 68Ga-DOTATATE which targets the somatostatin receptors abundantly expressed in neuroendocrine tumors, including bronchial carcinoid. This receptor targeted imaging technique permits targeting these tumors with therapeutic analogues such as 177Lu labeled DOTATATE. Overall, the proper utilization of PET in the thorax has the ability to directly impact and improve patient care.

Pitfalls of a Mixed Metabolic Response at PET/CT.

Although the term mixed metabolic response is commonly used in PET/CT reports, it should be a red flag to reconsider the assumptions made by the PET scan reader. Fluorine 18 fluorodeoxyglucose (FDG) PET/CT is recognized as an accurate imaging method for detecting response to cancer therapies. Critical clinical decisions regarding therapy are dependent on accurate interpretation of findings. The use of standardized terminology for response assessment, such as that in the Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST), is highly recommended. With PERCIST, treatment response is categorized as complete metabolic response, partial metabolic response, stable metabolic disease, or progressive metabolic disease. Mixed metabolic response is not included in PERCIST. Rather, it is used colloquially to describe a scenario in which scanning performed after systemic cancer therapy reveals divergent findings, with some tumor foci responding and others not responding or even seen progressing. In PERCIST, mixed metabolic response should be described as stable metabolic disease or progressive metabolic disease. However, the PET/CT reader may also wish to suggest that individual tumors have heterogeneous genetic and/or other characteristics and consequently a mixed response to therapy. The concept of tumor heterogeneity is gaining momentum in cancer research and thus possibly leading to options for therapy targeted to oligometastases that are not responding. However, the authors suggest exercising extreme caution when PET/CT findings appear at first to reflect what some might call a mixed response. In addition, they have found that FDG PET/CT findings are often confounding owing to the simultaneous presence of two or more unrelated disease processes. Common examples include synchronous neoplasms, inflammatory processes, and treatment-related effects. Thus, an apparent mixed response is a red flag to reconsider whether all of the FDG-avid findings are actually metastases of the same cancer. Common mimics of a mixed metabolic response that do not represent true tumor heterogeneity are highlighted to improve the FDG PET/CT reader's recognition of these lesions.©RSNA, 2019.

Osteolytic-variant POEMS syndrome: an uncommon presentation of "osteosclerotic" myeloma.

Polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes (POEMS) syndrome, a form of osteosclerotic myeloma, is a multisystem disease related to a monoclonal plasma cell proliferative disorder. Osseous lesions are most commonly sclerotic on radiographs and computed tomography (CT), demonstrate low T1 and T2 signal intensity on magnetic resonance imaging (MRI), and have variable degrees of avidity on positon emission tomography (PET) imaging using 18-fluorodeoxyglucose (18F-FDG). We present three cases of POEMS syndrome manifesting as osteolytic lesions with indolent features, including well-defined thin sclerotic rims, no cortical disruption or periosteal reaction, no associated soft-tissue mass, and a periarticular location, all features that could lead to misinterpretation as benign bone lesions. We also report increased T1 signal and diffuse solid enhancement of these lesions on MRI, features previously unreported. POEMS syndrome should not be discounted as a diagnostic consideration in the setting of osteolytic lesions with non-aggressive imaging characteristics on radiographs or CT, especially in the presence of other supportive clinical features.

Nuclear factor kappa B signaling regulates neuronal morphology and cocaine reward.

Although chronic cocaine-induced changes in dendritic spines on nucleus accumbens (NAc) neurons have been correlated with behavioral sensitization, the molecular pathways governing these structural changes, and their resulting behavioral effects, are poorly understood. The transcription factor, nuclear factor kappa B (NFkappaB), is rapidly activated by diverse stimuli and regulates expression of many genes known to maintain cell structure. Therefore, we evaluated the role of NFkappaB in regulating cocaine-induced dendritic spine changes on medium spiny neurons of the NAc and the rewarding effects of cocaine. We show that chronic cocaine induces NFkappaB-dependent transcription in the NAc of NFkappaB-Lac transgenic mice. This induction of NFkappaB activity is accompanied by increased expression of several NFkappaB genes, the promoters of which show chromatin modifications after chronic cocaine exposure consistent with their transcriptional activation. To study the functional significance of this induction, we used viral-mediated gene transfer to express either a constitutively active or dominant-negative mutant of Inhibitor of kappa B kinase (IKKca or IKKdn), which normally activates NFkappaB signaling, in the NAc. We found that activation of NFkappaB by IKKca increases the number of dendritic spines on NAc neurons, whereas inhibition of NFkappaB by IKKdn decreases basal dendritic spine number and blocks the increase in dendritic spines after chronic cocaine. Moreover, inhibition of NFkappaB blocks the rewarding effects of cocaine and the ability of previous cocaine exposure to increase an animal's preference for cocaine. Together, these studies establish a direct role for NFkappaB pathways in the NAc to regulate structural and behavioral plasticity to cocaine.

Overexpression of 5-HT1B receptor in dorsal raphe nucleus using Herpes Simplex Virus gene transfer increases anxiety behavior after inescapable stress.

5-HT(1B) autoreceptors have been implicated in animal models of stress and are regulated selectively by serotonin-selective reuptake inhibitors such as fluoxetine. These terminal autoreceptors regulate serotonin release from dorsal raphe nucleus (DRN) projections throughout rat forebrain. However, it has not been previously possible to manipulate 5-HT(1B) autoreceptor activity selectively without also changing 5-HT(1B) activity in other neurons mediating different behavioral responses. Therefore, we have developed a viral-mediated gene transfer strategy to express hemagglutinin-tagged 5-HT(1B) and manipulate these autoreceptors in DRN. Green fluorescent protein (GFP) was coexpressed from a separate transcriptional unit on the same amplicon to assist in monitoring infection and expression. We confirmed the expression and biological activity of both transgenic proteins in vitro. When injected directly into DRN using stereotaxic procedure, HA-5-HT(1B) receptors were expressed in serotonergic neurons and translocated to the forebrain. The effect of DRN expression of HA-5-HT(1B) on stress-induced behaviors was compared with control rats that received GFP-only amplicons. There was no change in immobility in the forced swim test. However, HA-5-HT(1B) expression significantly reduced entrances into the central region of an open-field arena after water-restraint stress without altering overall locomotor activity, but not in the absence of stress exposure. HA-5-HT(1B) expression also reduced entries into the open arms of the elevated plus maze after water restraint. Because these tests are sensitive to increases in anxiety-like behavior, our results suggest that overactivity of 5-HT(1B) autoreceptors in DRN neurons may be an important mediator of pathological responses to stressful events.