Prospective Pilot Study of 18F-Fluoroestradiol PET/CT in Patients With Invasive Lobular Carcinomas.

BACKGROUND. PET/CT with 18F-fluoroestradiol (FES) (FDA-approved in 2020) depicts tissues expressing estrogen receptor (ER). Invasive lobular carcinoma (ILC) is commonly ER positive. OBJECTIVE. The primary aim of this study was to assess the frequency with which sites of histologically proven ILC have abnormal uptake on FES PET/CT. METHODS. This prospective single-center pilot study, conducted from December 2020 to August 2021, enrolled patients with histologically confirmed ILC to undergo FES PET/CT; patients optionally underwent FDG PET/CT. Two nuclear radiologists assessed FES PET/CT and FDG PET/CT studies for abnormal uptake corresponding to known ILC sites at enrollment and for additional sites of abnormal uptake, resolving differences by consensus. The primary endpoint was percentage of known ILC sites showing abnormal FES uptake. The alternative to the null hypothesis was that more than 60% of sites would have abnormal FES uptake, exceeding the percentage of ILC with abnormal FDG uptake described in prior literature. A sample size of 24 biopsied lesions was preselected to provide 81% power for the alternative hypothesis (one-sided α = .10). Findings on FES PET/CT and FDG PET/CT were summarized for additional secondary endpoints. RESULTS. The final analysis included 17 patients (mean age, 59.1 ± 13.2 years) with 25 sites of histologically confirmed ILC at enrollment (22 breast lesions, two axillary lymph nodes, one distant metastasis). FES PET/CT showed abnormal uptake in 22 of 25 (88%) lesions, sufficient to reject the null hypothesis (p = .002). Thirteen patients underwent FDG PET/CT. Four of 23 (17%) sites of histologically confirmed ILC, including additional sites detected and confirmed after enrollment, were identified with FES PET/CT only, and 1 of 23 (4%) was identified only with FDG PET/CT (p = .18). FES PET/CT depicted additional lesions not detected with standard-of-care evaluation in 4 of 17 (24%) patients (two contralateral breast cancers and two metastatic axillary lymph nodes, all with subsequent histologic confirmation). Use of FES PET/CT resulted in changes in clinical stage with respect to standard-of-care evaluation in 3 of 17 (18%) patients. CONCLUSION. The primary endpoint of the trial was met. The frequency of abnormal FES uptake among sites of histologically known ILC was found to be to be significantly greater than 60%. CLINICAL IMPACT. This pilot study shows a potential role of FES PET/CT in evaluation of patients with ILC. TRIAL REGISTRATION. ClinicalTrials.gov NCT04252859.

Biopsy of a complicated right atrial mass using CARTO 3-dimensional electro-anatomic mapping.

We report the successful biopsy of a right atrial fatty mass using CARTO 3-dimensional electro-anatomic mapping fused with cardiac MRI. Fluoroscopic guidance within the cardiac chambers lacks precision and therefore risks geographical miss of the intended target and cardiac perforation. CARTO mapping fused with cardiac MRI facilitated precise navigation of the bioptome thereby ensuring a successful biopsy of the intended tissue while minimizing the risks of inadvertent trauma to adjacent tissue.

Protective autophagy elicited by RAF→MEK→ERK inhibition suggests a treatment strategy for RAS-driven cancers.

Pancreatic ductal adenocarcinoma (PDA) was responsible for ~ 44,000 deaths in the United States in 2018 and is the epitome of a recalcitrant cancer driven by a pharmacologically intractable oncoprotein, KRAS1-4. Downstream of KRAS, the RAF→MEK→ERK signaling pathway plays a central role in pancreatic carcinogenesis5. However, paradoxically, inhibition of this pathway has provided no clinical benefit to patients with PDA6. Here we show that inhibition of KRAS→RAF→MEK→ERK signaling elicits autophagy, a process of cellular recycling that protects PDA cells from the cytotoxic effects of KRAS pathway inhibition. Mechanistically, inhibition of MEK1/2 leads to activation of the LKB1→AMPK→ULK1 signaling axis, a key regulator of autophagy. Furthermore, combined inhibition of MEK1/2 plus autophagy displays synergistic anti-proliferative effects against PDA cell lines in vitro and promotes regression of xenografted patient-derived PDA tumors in mice. The observed effect of combination trametinib plus chloroquine was not restricted to PDA as other tumors, including patient-derived xenografts (PDX) of NRAS-mutated melanoma and BRAF-mutated colorectal cancer displayed similar responses. Finally, treatment of a patient with PDA with the combination of trametinib plus hydroxychloroquine resulted in a partial, but nonetheless striking disease response. These data suggest that this combination therapy may represent a novel strategy to target RAS-driven cancers.

Publisher Correction: Protective autophagy elicited by RAF→MEK→ERK inhibition suggests a treatment strategy for RAS-driven cancers.

In the version of this article initially published, the label over the bottom schematic in Fig. 1a was "pH > 5.0"; it should have been "pH < 5.0". Further, the original article misspelt the surname of Katrin P. Guillen as "Gullien". These errors have been corrected in the print, PDF and HTML versions of the article.

Mentoring and the Nuclear Medicine Technologist.

Mentoring has a rich tradition throughout history. Capable instructors and experienced nuclear medicine technologists guide the path of the new trainee, with success being determined by the quality of the mentorship that takes place. This article provides an overview of mentoring for nuclear medicine technologists, including what it is, how it can work, and what benefits it may provide. Advice on improved application of mentoring is also presented.

18F-FDG and Amyloid PET in Dementia.

We present a case of memory loss and aphasia in a 72-y-old man and discuss how PET imaging supported a diagnosis of Alzheimer dementia despite conflicting clinical findings.

Correlation of Glioma Proliferation and Hypoxia by Luciferase, Magnetic Resonance, and Positron Emission Tomography Imaging.

Gliomas are the most common type of primary, malignant brain tumor and significantly impact patients, who have a median survival of ~1 year depending on mutational background. Novel imaging modalities such as luciferase bioluminescence, micro-magnetic resonance imaging (micro-MRI), micro-computerized tomography (micro-CT), and micro-positron emission tomography (micro-PET) have expanded the portfolio of tools available to study this disease. Hypoxia, a key oncogenic driver of glioma and mechanism of resistance, can be studied in vivo by the concomitant use of noninvasive MRI and PET imaging. We present a protocol involving stereotactic injection of syngenic F98 luciferase-expressing glioma cells generated by our laboratory into Fischer 344 rat brains and imaging using luciferase. In addition, 18-F-fludeoxyglucose, 18F-fluoromisonidazole, and 18F-fluorothymidine PET imaging are compared with quantified luciferase flux. These tools can potentially be used for assessing tumor growth characteristics, hypoxia, mutational effects, and treatment effects.

The Influential Role of BCL2 Family Members in Synovial Sarcomagenesis.

Synovial sarcomas are deadly soft tissue malignancies associated with t(X;18) balanced chromosomal translocations. Expression of the apoptotic regulator BCL2 is prominent in synovial sarcomas and has prompted the hypothesis that synovial sarcomagenesis may depend on it. Herein, it is demonstrated that Bcl2 overexpression enhances synovial sarcomagenesis in an animal model. Furthermore, we determined increased familial clustering of human synovial sarcoma patients with victims of other BCL2-associated malignancies in the Utah Population Database. Conditional genetic disruption of Bcl2 in mice also led to reduced sarcomagenesis. Pharmacologic inhibition specific to BCL2 had no demonstrable efficacy against human synovial sarcoma cell lines or mouse tumors. However, targeting BCLxL in human and mouse synovial sarcoma with the small molecule BH3 domain inhibitor, BXI-72, achieved significant cytoreduction and increased apoptotic signaling. Thus, the contributory role of BCL2 in synovial sarcomagenesis does not appear to render it as a therapeutic target, but mitochondrial antiapoptotic BCL2 family members may be.Implications: The association of BCL2 expression with synovial sarcoma is found to fit with a subtle, but significant, impact of its enhanced presence or absence during early tumorigenesis. However, specific pharmacologic inhibition of BCL2 does not demonstrate a persistent dependence in fully developed tumors. Conversely, inhibition of the BCL2 family member BCLxL resulted in nanomolar potency against human synovial sarcoma cell lines and 50% tumor reduction in a genetically engineered mouse model. Mol Cancer Res; 15(12); 1733-40. ©2017 AACR.

Relationship between 18F-Flutemetamol uptake and RBANS performance in non-demented community-dwelling older adults.

OBJECTIVE: The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) has been used extensively for clinical care and in research for patients with mild cognitive impairment and Alzheimer's disease (AD); however, relatively few studies have evaluated the relationship between RBANS performance and AD imaging biomarkers. The purpose of the current study was to evaluate the association between a relatively new amyloid positron emission tomography imaging biomarker and performance on the RBANS. METHODS: Twenty-seven nondemented community-dwelling adults over the age of 65 underwent 18F-Flutemetamol amyloid- positron emission tomography imaging, along with cognitive testing using the RBANS and select behavioral measures. Partial correlation coefficients were used to identify relationships between the imaging and behavioral markers. RESULTS: After controlling for age and education, amyloid deposition and RBANS Indexes of Immediate Memory, Delayed Memory, and Total Scale score were significantly correlated (p's < .001, r's = -.73 to -.77, d's = 2.13-2.39), with greater amyloid burden being associated with lower RBANS scores. The Delayed Memory Index was particularly highly associated with 18F-Flutemetamol binding (r2 = .59, p < .001, d = 2.39). Neither 18F-Flutemetamol binding nor RBANS performance was significantly correlated with levels of depression, subjective cognitive difficulties, or premorbid intellect. CONCLUSIONS: Because of the limited use of amyloid imaging in clinical settings due to high cost and lack of reimbursement, these findings suggest that in particular RBANS Delayed Memory Index may be a cost-efficient tool to identify early signs of AD pathology, and its use may enlighten clinical decision-making regarding potential progression to dementia due to AD.

Amyloid Positivity Using [18F]Flutemetamol-PET and Cognitive Deficits in Nondemented Community-Dwelling Older Adults.

Little research exists examining the relationship between beta-amyloid neuritic plaque density via [18F]flutemetamol binding and cognition; consequently, the purpose of the current study was to compare cognitive performances among individuals having either increased amyloid deposition (Flute+) or minimal amyloid deposition (Flute-). Twenty-seven nondemented community-dwelling adults over the age of 65 underwent [18F]flutemetamol amyloid-positron emission tomography imaging, along with cognitive testing using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and select behavioral measures. Analysis of variance was used to identify the differences among the cognitive and behavioral measures between Flute+/Flute- groups. Flute+ participants performed significantly worse than Flute- participants on RBANS indexes of immediate memory, language, delayed memory, and total scale score, but no significant group differences in the endorsed level of depression or subjective report of cognitive difficulties were observed. Although these results are preliminary, [18F]flutemetamol accurately tracks cognition in a nondemented elderly sample, which may allow for better prediction of cognitive decline in late life.

Usefulness of left atrial appendage volume as a predictor of embolic stroke in patients with atrial fibrillation.

Stroke prevention in atrial fibrillation (AF) is guided by clinical factors with inadequate predictive power. Most thrombi observed in AF are observed in the left atrial appendage (LAA). This study was designed to determine (1) the association between LAA and the incidence of AF-related stroke and (2) the power of LAA to predict stroke. Patients (n = 48) with a history of AF and stroke were compared with control subjects (n = 48) with a history of AF but no history of stroke. Magnetic resonance images from both case and control populations were manually segmented to determine LAA volume. Patients with a history of stroke had larger LAA mean volumes than control subjects (28.8 ± 13.5 cm(3) vs 21.7 ± 8.27 cm(3), p = 0.002). Stroke risk is highest in patients with a LAA volume >34 cm(3) (multivariable OR 7.11, p = 0.003). In conclusion, larger LAA volume is associated with stroke in the setting of AF, and this measure can potentially improve risk stratification for stroke risk management in AF patients.