Increased 18F-FDG Uptake in the Axillary Lymph Nodes of the Vaccinated Side Associated with COVID-19 Vaccination.

A 50-year-old female patient underwent (18fluorine-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) following modified radical mastectomy for cancer of the left breast. Ten days before the PET/CT, the coronavirus disease-2019 (COVID-19) vaccine was injected intramuscularly into the right deltoid muscle. Increased (18F-FDG uptake of maximum standardized uptake value (11.0) was observed in the lymph nodes of the right axilla, which had not been observed in the previous PET/CT. The size of the oval-shaped lymph nodes was up to approximately 11×9 mm; however, it was larger than that observed on the previous PET/CT. We contemplate that the increased (18F-FDG uptake was a reactive change in the lymph nodes associated with the COVID-19 vaccine.

Prolonged generalized immune response on 18F-FDG PET/CT following COVID-19 vaccination.

The Coronavirus disease 2019 (COVID-19) pandemic continues to be a major public health concern affecting millions of people globally. The COVID-19 vaccination has implications in medical assessment of cancer patients especially undergoing diagnostic imaging such as 18F-fluoro-deoxyglucose (FDG) positron emission tomography with computed tomography (PET/CT). The inflammatory changes following vaccination can cause false positive findings on imaging. We present a case of a patient with esophageal carcinoma who had 18F-FDG PET/CT scan, 8 weeks following booster dose of Moderna COVID-19 vaccination, which showed widespread FDG avid reactive lymph nodes and intense splenic uptake for prolonged duration of approximately 8 months (34 weeks) probably representing generalized immune response. It is important from radiological/nuclear medicine perspective to recognize imaging features of such rare effect of COVID-19 vaccination, which can pose a challenge in assessing 18F-FDG PET/CT scans in cancer patients. It has also opened new avenues for future research evaluating such COVID-19 vaccine-related prolonged systemic immunological response in cancer patients.

COVID-19 vaccination-related [18F]FDG-avid lymph node in a patient with marginal zone B-cell lymphoma

The [18F]FDG PET/CT is a crucial tool in the diagnostic process and monitoring of neoplastic diseases. Currently, during the global program of vaccination against COVID-19 and the possibility of axillary lymphadenopathy after this injection, the correct interpretation of PET/CT images is vitally significant and may create some difficulties. We present a case of increased uptake of [18F]FDG in an axillary lymph node in a PET/CT scan performed 2 days after the Pfizer BioNTech COVID-19 vaccine in a 48-year-old patient newly diagnosed with marginal zone B-cell lymphoma.Copyright © 2023 Via Medica.

COVID-19 vaccine related hypermetabolic lymph nodes on PET/CT: Implications of inflammatory findings in cancer imaging.

We observed several patients presenting 2-[18F]FDG uptake in the reactive axillary lymph node at PET/CT imaging, ipsilateral to the site of the COVID-19 vaccine injection. Analog finding was documented at [18F]Choline PET/CT. The aim of our study was to describe this source of false positive cases. All patients examined by PET/CT were included in the study. Data concerning patient anamnesis, laterality, and time interval from recent COVID-19 vaccination were recorded. SUVmax was measured in all lymph nodes expressing tracer uptake after vaccination. Among 712 PET/CT scans with 2-[18F]FDG, 104 were submitted to vaccination; 89/104 patients (85%) presented axillary and/or deltoid tracer uptake, related to recent COVID-19 vaccine administration (median from injection: 11 days). The mean SUVmax of these findings was 2.1 (range 1.6-3.3). Among 89 patients with false positive axillary uptake, 36 subjects had received chemotherapy due to lymph node metastases from somatic cancer or lymphomas, prior to the scan: 6/36 patients with lymph node metastases showed no response to therapy or progression disease. The mean SUVmax value of lymph nodal localizations of somatic cancers/lymphomas after chemotherapy was 7.8. Only 1/31 prostate cancer patients examined by [18F]Choline PET/CT showed post-vaccine axillary lymph node uptake. These findings were not recorded at PET/CT scans with [18F]-6-FDOPA, [68Ga]Ga-DOTATOC, and [18F]-fluoride. Following COVID-19 mass vaccination, a significant percentage of patients examined by 2-[18F]FDG PET/CT presents axillary, reactive lymph node uptake. Anamnesis, low-dose CT, and ultrasonography facilitated correct diagnosis. Semi-quantitative assessment supported the visual analysis of PET/CT data; SUVmax values of metastatic lymph nodes were considerably higher than post-vaccine lymph nodes. [18F]Choline uptake in reactive lymph node after vaccination was confirmed. After the COVID-19 pandemic, nuclear physicians need to take these potential false positive cases into account in daily clinical practice.

Positron Emission Tomography with Computed Tomography in Evaluations of Classical Fever of Unknown Origin and Length of Hospitalization: A 10-Year Medical Record Review of a Tertiary Hospital

Background: Positron emission tomography with computed tomography (PET/CT) has proven its value for the differential diagnosis of fever of unknown origin (FUO). However, the extent to which PET/CT during FUO evaluation can shorten the length of hospital stay (LOS) remains unclear. Materials and Methods: A retrospective review of the medical records over a 10-year period from January 2009 to December 2018 of a tertiary university hospital was performed. The inclusion criteria were symptoms with fever persisting for >3 weeks before admission, as defined in classical FUO. Medical records in which PET/CT was performed after the final diagnosis, such as neoplastic causes, were excluded. Moreover, in the neoplasm category evaluated using PET/CT, only diagnostic PET/CT cases were enrolled;PET/CT cases for confirming metastasis or staging were excluded. Final diagnoses were categorized as infection, neoplasm, noninfectious non-neoplastic inflammatory disorder, miscellaneous, and uncategorizable. Each category was separated into evaluation with and without PET/CT for statistical analyses. Results: In total, 91 patients underwent evaluation for FUO and about one in three underwent PET/CT. Overall LOS was not different between the PET/CT and non-PET/CT groups;however, there were differences in LOS within the categories. For infectious causes, the mean LOS was 21.1 and 11.1 days in the PET/CT and non-PET/CT groups, respectively (P = 0.022). For neoplastic causes, the mean LOS was 11.4 and 36.0 days in the PET/CT and non-PET/CT Conclusion: Most patients with FUO were aged 50 - 60 years, and their family and work roles were crucial. A lower LOS may benefit both the patients' families and society at large. Interestingly, PET/CT may contribute to shortening the LOS during FUO evaluation when the causes are neoplastic, by approximately 24 days.

The Effects of CoronaVac (Sinovac) and BNT162b2 (BioNTech/Pfizer) Vaccination on Oncologic 18F-FDG PET/CT Studies.

Objectives: BioNTech (Pfizer) and CoronaVac (Sinovac) vaccines are two of the most administered coronavirus disease-2019 (COVID-19) vaccines worldwide. Vaccination against severe acute respiratory syndrome-coronavirus-2 has caused a diagnostic challenge in oncological 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) studies. The aim of our study was to evaluate the 18F-FDG PET/CT findings of the two most commonly administered vaccines worldwide. Methods: Patients over 18 years old who underwent 18F-FDG PET/CT for oncological purposes in our institution between January 13, 2021 and January 31, 2022, who received a single or second dose of the BioNTech or CoronaVac vaccines in the last two months, were included in the study. Descriptive analyses were presented as mean, standard deviation, frequency and ratio. Additionally, chi-square test was used to analyze categorical variables. Results: Ipsilateral deltoid muscle hypermetabolism was observed in 6.9% (n=15) and 14.3% (n=22) patients who received CoronaVac and BioNTech vaccines, respectively. Ipsilateral axillary lymph node hypermetabolism was observed in 11% (n=24) and 41.6% (n=64) patients who received CoronaVac and BioNTech vaccines, respectively. Synchronous deltoid muscle and axillary lymph node hypermetabolism was observed in 4.14% (n=9) and 12.33% (n=19) patients who received CoronaVac and BioNTech vaccines, respectively. Significant differences were detected between CoronaVac and BioNTech vaccines in terms of ipsilateral deltoid muscle hypermetabolism, ipsilateral axillary lymph node hypermetabolism and synchronous deltoid muscle and axillary lymph node hypermetabolism (p<0.05). Conclusion: COVID-19 vaccination may result in ipsilateral axillary lymph node hypermetabolism, ipsilateral deltoid muscle hypermetabolism, or synchronous deltoid muscle and axillary lymph node hypermetabolism with different frequencies depending on the type of vaccination. Although synchronous deltoid muscle and axillary lymph node hypermetabolism can reduce misinterpretation of 18F-FDG PET/CT, to avoid misinterpretation, it is important to question the vaccination history during ongoing COVID-19 vaccination process.

COVID-19 Pneumonia was Incidentally Detected on 18F-Fluorocholine PET/CT in a Work-up for Prostate Cancer.

This is a presentation of the case of a patient who underwent 18F-fluorocholine positron emission/computed tomography to stage a prostate cancer with incidentally found bilateral pneumonia. A high prevalence of incidental pneumonia is very probable under the current circumstance of coronavirus disease-2019 (COVID-19) pandemic, and oncological patients are at increased risk of COVID-19 with poorer outcome. The lung inflammatory burden in the case of COVID-19 infection can be demonstrated by 18F-fluorocholine.

COVID-19: Findings in nuclear medicine from head to toe.

COVID-19 is a multisystemic disease, and hence its potential manifestations on nuclear medicine imaging can extend beyond the lung. Therefore, it is important for the nuclear medicine physician to recognize these manifestations in the clinic. While FDG-PET/CT is not indicated routinely in COVID-19 evaluation, its unique capability to provide a functional and anatomical assessment of the entire body means that it can be a powerful tool to monitor acute, subacute, and long-term effects of COVID-19. Single-photon scintigraphy is routinely used to assess conditions such as pulmonary embolism, cardiac ischemia, and thyroiditis, and COVID-19 may present in these studies. The most common nuclear imaging finding of COVID-19 vaccination to date is hypermetabolic axillary lymphadenopathy. This may pose important diagnostic and management dilemmas in oncologic patients, particularly those with malignancies where the axilla constitutes a lymphatic drainage area. This article aims to summarize the relevant literature published since the beginning of the pandemic on the intersection between COVID-19 and nuclear medicine.

Longitudinal analyses using 18F-Fluorodeoxyglucose positron emission tomography with computed tomography as a measure of COVID-19 severity in the aged, young, and humanized ACE2 SARS-CoV-2 hamster models.

This study compared disease progression of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in three different models of golden hamsters: aged (≈60 weeks old) wild-type (WT), young (6 weeks old) WT, and adult (14-22 weeks old) hamsters expressing the human-angiotensin-converting enzyme 2 (hACE2) receptor. After intranasal (IN) exposure to the SARS-CoV-2 Washington isolate (WA01/2020), 2-deoxy-2-[fluorine-18]fluoro-D-glucose positron emission tomography with computed tomography (18F-FDG PET/CT) was used to monitor disease progression in near real time and animals were euthanized at pre-determined time points to directly compare imaging findings with other disease parameters associated with coronavirus disease 2019 (COVID-19). Consistent with histopathology, 18F-FDG-PET/CT demonstrated that aged WT hamsters exposed to 105 plaque forming units (PFU) developed more severe and protracted pneumonia than young WT hamsters exposed to the same (or lower) dose or hACE2 hamsters exposed to a uniformly lethal dose of virus. Specifically, aged WT hamsters presented with a severe interstitial pneumonia through 8 d post-exposure (PE), while pulmonary regeneration was observed in young WT hamsters at that time. hACE2 hamsters exposed to 100 or 10 PFU virus presented with a minimal to mild hemorrhagic pneumonia but succumbed to SARS-CoV-2-related meningoencephalitis by 6 d PE, suggesting that this model might allow assessment of SARS-CoV-2 infection on the central nervous system (CNS). Our group is the first to use (18F-FDG) PET/CT to differentiate respiratory disease severity ranging from mild to severe in three COVID-19 hamster models. The non-invasive, serial measure of disease progression provided by PET/CT makes it a valuable tool for animal model characterization.

Pulmonary Findings of [18F]FDG PET/CT Images on Asymptomatic COVID-19 Patients.

During the coronavirus disease 2019 (COVID-19) pandemic, several case studies demonstrated that many asymptomatic patients with COVID-19 underwent fluorine-18 fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) examination for various indications. However, there is a lack of literature to characterize the pattern of [18F]FDG PET/CT imaging on asymptomatic COVID-19 patients. Therefore, a systematic review to analyze the pulmonary findings of [18F]FDG PET/CT on asymptomatic COVID-19 patients was conducted. This systematic review was performed under the guidelines of PRISMA. PubMed, Medline, and Web of Science were used to search for articles for this review. Articles with the key words: "asymptomatic", "COVID-19", "[18F]FDG PET/CT", and "nuclear medicine" were searched for from 1 January 2020 to 20 May 2021. Thirty asymptomatic patients with COVID-19 were included in the eighteen articles. These patients had a mean age of 62.25 ± 14.85 years (male: 67.71 ± 12.00; female: 56.79 ± 15.81). [18F]FDG-avid lung lesions were found in 93.33% (28/30) of total patients. The major lesion was [18F]FDG-avid multiple ground-glass opacities (GGOs) in the peripheral or subpleural region in bilateral lungs, followed by the consolidation. The intensity of [18F]FDG uptake in multiple GGOs was 5.605 ± 2.914 (range from 2 to 12) for maximal standardized uptake value (SUVmax). [18F]FDG-avid thoracic lymph nodes (LN) were observed in 40% (12/40) of the patients. They mostly appeared in both mediastinal and hilar regions with an SUVmax of 5.8 ± 2.93 (range from 2.5 to 9.6). The [18F]FDG uptake was observed in multiple GGOs, as well as in the mediastinal and hilar LNs. These are common patterns in PET/CT of asymptomatic patients with COVID-19.

[68Ga]Ga-Pentixafor PET/CT uptake due to COVID-19 infection: An incidental finding in a patient with high-grade oligodendroglioma

A 56-year-old woman with new-onset aphasia and mood changes was diagnosed with a left temporal mass. The surgery was done. She was referred for a trial of post-operative study of in vivo evaluation of CXCR4 expression using [68Ga]Ga-Pentixafor (Pars-CixaforTM) PET/CT in high-grade glioma. The imaging from the brain revealed no evidence of tumoral remnant. Furthermore, the patient represented positive COVID-19 PCR about 4 weeks prior to the study. Surprisingly, mild diffuse uptake was noted in the base and periphery of both lungs with ground glass opacities (GGO) and consolidations (SUVmax = 2.60) with CXCR4-avid hilar lymph nodes (SUVmax up to 3.42).Copyright © 2023 The Authors.

Axillary Lymph Node Uptake on 18F-FDG PET/CT after COVID-19 Vaccination: A Direct Comparison Study with Influenza Vaccination.

Objectives: To compare vaccinated-side axillary lymph node uptake on 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) after coronavirus disease-2019 (COVID-19) and influenza vaccination. Methods: We retrospectively analyzed 177 patients who underwent 18F-FDG PET/CT after COVID-19 or influenza vaccination. We compared the uptake of the vaccinated-side axillary lymph nodes of 109 COVID-19 vaccinated patients with those of a lot of influenza-vaccinated patients. We also compared the uptake between 66 patients who received the first COVID-19 vaccination with 43 who received the second COVID-19 vaccination. Results: 18F-FDG-avid axillary lymph nodes on the vaccinated side were significantly more frequently observed in the COVID-19 group (45%) than in the influenza group (19%) (p<0.001). When the interval between vaccination to PET/CT was within 7 days, there was no significant difference in the frequency of 18F-FDG-avid vaccinated-side axillary lymph nodes between the groups (COVID-19 group: 41% vs. influenza group: 45%, p=0.724). When the interval was over 7 days, 18F-FDG-avid lymph nodes were much more frequent in the COVID-19 group (47%) than in the influenza group (7%) (p<0.001). Comparing the first and second COVID-19 groups, 18F-FDG-avid lymph nodes were more frequent in the second vaccination group than in the first vaccination group, but the difference was not significant. Conclusion: 18F-FDG-avid vaccinated-side axillary lymph nodes were more frequently observed in the COVID-19 group than in the influenza group. In the case of the COVID-19 vaccine, a delay of 18F-FDG PET/CT examination is recommended by a longer interval from vaccination than in the influenza vaccine.

[18F]FDG-PET/CT in mechanically ventilated critically ill patients with COVID-19 ARDS and persistent inflammation.

Purpose: We report the findings of four critically ill patients who underwent an [18F]FDG-PET/CT because of persistent inflammation during the late phase of their COVID-19. Methods: Four mechanically ventilated patients with COVID-19 were retrospectively discussed in a research group to evaluate the added value of [18F]FDG-PET/CT. Results: Although pulmonary PET/CT findings differed, bilateral lung anomalies could explain the increased CRP and leukocytes in all patients. This underscores the limited ability of the routine laboratory to discriminate inflammation from secondary infections. Based on PET/CT findings, a secondary infection/inflammatory focus was suspected in two patients (pancreatitis and gastritis). Lymphadenopathy was present in patients with a detectable SARS-CoV-2 viral load. Muscle uptake around the hips or shoulders was observed in all patients, possibly due to the process of heterotopic ossification. Conclusion: This case series illustrates the diagnostic potential of [18F]FDG-PET/CT imaging in critically ill patients with persistent COVID-19 for the identification of other causes of inflammation and demonstrates that this technique can be performed safely in mechanically ventilated critically ill patients.

Imaging Fibrosis.

Tissue injury in nonmalignant human disease can develop from either disproportionate inflammation or exaggerated fibrotic responses. The molecular and cellular fundamental of these 2 processes, their impact on disease prognosis and the treatment concept deviates fundamentally. Consequently, the synchronous assessment and quantification of these 2 processes in vivo is extremely desirable. Although noninvasive molecular techniques such as 18F-fluorodeoxyglucose PET offer insights into the degree of inflammatory activity, the assessment of the molecular dynamics of fibrosis remains challenging. The 68Ga-fibroblast activation protein inhibitor-46 may improve noninvasive clinical diagnostic performance in patients with both fibroinflammatory pathology and long-term CT-abnormalities after severe COVID-19.

Time-related aortic inflammatory response, as assessed with 18F-FDG PET/CT, in patients hospitalized with severely or critical COVID-19: the COVAIR study.

AIM: Arterial involvement has been implicated in the coronavirus disease of 2019 (COVID-19). Fluorine 18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) imaging is a valuable tool for the assessment of aortic inflammation and is a predictor of outcome. We sought to prospectively assess the presence of aortic inflammation and its time-dependent trend in patients with COVID-19. METHODS: Between November 2020 and May 2021, in this pilot, case-control study, we recruited 20 patients with severe or critical COVID-19 (mean age of 59 ± 12 years), while 10 age and sex-matched individuals served as the control group. Aortic inflammation was assessed by measuring 18F-FDG uptake in PET/CT performed 20-120 days post-admission. Global aortic target to background ratio (GLA-TBR) was calculated as the sum of TBRs of ascending and descending aorta, aortic arch, and abdominal aorta divided by 4. Index aortic segment TBR (IAS-TBR) was designated as the aortic segment with the highest TBR. RESULTS: There was no significant difference in aortic 18F-FDG PET/CT uptake between patients and controls (GLA-TBR: 1.46 [1.40-1.57] vs. 1.43 [1.32-1.70], respectively, P = 0.422 and IAS-TBR: 1.60 [1.50-1.67] vs. 1.50 [1.42-1.61], respectively, P = 0.155). There was a moderate correlation between aortic TBR values (both GLA and IAS) and time distance from admission to 18F-FDG PET-CT scan (Spearman's rho = - 0.528, P = 0.017 and Spearman's rho = - 0.480, p = 0.032, respectively). Patients who were scanned less than or equal to 60 days from admission (n = 11) had significantly higher GLA-TBR values compared to patients that were examined more than 60 days post-admission (GLA-TBR: 1.53 [1.42-1.60] vs. 1.40 [1.33-1.45], respectively, P = 0.016 and IAS-TBR: 1.64 [1.51-1.74] vs. 1.52 [1.46-1.60], respectively, P = 0.038). There was a significant difference in IAS- TBR between patients scanned ≤ 60 days and controls (1.64 [1.51-1.74] vs. 1.50 [1.41-1.61], P = 0.036). CONCLUSION: This is the first study suggesting that aortic inflammation, as assessed by 18F-FDG PET/CT imaging, is increased in the early post COVID phase in patients with severe or critical COVID-19 and largely resolves over time. Our findings may have important implications for the understanding of the course of the disease and for improving our preventive and therapeutic strategies.

Novel 68Ga-FAPI PET/CT offers oncologic staging without COVID-19 vaccine-related pitfalls.

In the setting of ongoing SARS-CoV-2 vaccination, vaccine-related tracer uptake in locoregional lymph nodes has become a well-known issue in tumor staging by 18F-FDG PET/CT. 68Ga-FAPI PET/CT is a new oncologic imaging tool that may overcome this limitation. Methods: We assessed post-vaccine, head-to-head and same-day 18F-FDG and 68Ga-FAPI-46 PET/CT findings in a series of 11 patients from a large prospective imaging registry. All patients with documented tracer uptake in locoregional lymph nodes on PET/CT or PET/MRI, following vaccination within 6 weeks, were eligible for investigation. Result: Significant visual lymph node uptake adjacent to the injection site was noted in 11/11 (100%) patients with 18F-FDG PET/CT versus 0/11 (0%) with 68Ga-FAPI PET/CT. 18F-FDG detected 73% and 68Ga-FAPI PET/CT 94% of all tumor lesions. Conclusion: In this case-series study, 68Ga-FAPI showed its potential to avoid 18F-FDG-PET/CT post-vaccination pitfalls and presented superior tumor localization.

Imaging of COVID-19 Vaccine-Related Axillary Lymphadenopathy: Initial Outcomes Based on US Features of Axillary Lymph Nodes

Objective: The purpose of this study is to describe the imaging characteristics and outcomes of COVID-19 vaccine-related axillary adenopathy and subsequent follow-up.

COVID-19-Associated Erythema Nodosum Detected on FDG PET/CT.

We report the case of a 69-year-old woman who underwent 18F-FDG PET/CT due to prolonged fever. One month before, the patient was diagnosed with COVID-19 infection. The 18F-FDG PET/CT showed several subcutaneous nodules with 18F-FDG uptake on the thorax and upper extremities and bilateral lung infiltrates due to organizing pneumonitis. Clinical examination revealed multiple tender nodules on thorax, arms, and legs, consistent with erythema nodosum (EN) induced by COVID-19 infection. The woman was treated with prednisone with a good effect on EN. To our knowledge, this is the first report on EN secondary to COVID-19 infection diagnosed on 18F-FDG PET/CT.

In Vivo Visualization and Quantification of Neutrophil Elastase in Lungs of COVID-19 Patients - A First-In-Human Positron Emission Tomography Study with 11C-GW457427.

COVID-19 can cause life-threatening lung-inflammation that is suggested to be mediated by neutrophils, whose effector mechanisms in COVID-19 is inexplicit. The aim of the present work is to evaluate a novel PET tracer for neutrophil elastase in COVID-19 patients and healthy controls. METHODS: In this open-label, First-In-Man study, four patients with hypoxia due to COVID-19 and two healthy controls were investigated with positron emission tomography (PET) using the new selective and specific neutrophil elastase PET-tracer [11C]GW457427 and [15O]water for the visualization and quantification of NE and perfusion in the lungs, respectively. RESULTS: [11C]GW457427 accumulated selectively in lung areas with ground-glass opacities on computed tomography characteristic of COVID-19 suggesting high levels on NE in these areas. In the same areas perfusion was severely reduced in comparison to healthy lung tissue as measured with [15O]water. CONCLUSION: The data suggests that NE may be responsible for the severe lung inflammation in COVID-19 patients and that inhibition of NE could potentially reduce the acute inflammatory process and improve the condition.