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 Molecular Imaging of the Major Neurodegenerative Disorders: Overview and Pictorial Essay, from a Nuclear Medicine Center's Perspective.

Computed tomography (CT) and magnetic resonance imaging (MRI) provide key structural information on brain pathophysiology. Positron emission tomography (PET) measures metabolism in the living brain; it plays an important role in molecular neuroimaging and is rapidly expanding its field of application to the study of neurodegenerative diseases. Different PET radiopharmaceuticals allow in vivo characterization and quantization of biological processes at the molecular and cellular levels, from which many neurodegenerative diseases develop. In addition, hybrid imaging tools such as PET/CT and PET/MRI support the utility of PET, enabling the anatomical mapping of functional data. In this overview, we describe the most commonly used PET tracers in the diagnostic work-up of patients with Alzheimer's disease, Parkinson's disease, and other neurodegenerative diseases. We also briefly discuss the pathophysiological processes of tracer uptake in the brain, detailing their specific cellular pathways in clinical cases. This overview is limited to imaging agents already applied in human subjects, with particular emphasis on those tracers used in our department.

Peptide Receptor Radionuclide Therapy and Primary Brain Tumors: An Overview.

Primary brain tumors (PBTs) are some of the most difficult types of cancer to treat, and despite advancements in surgery, chemotherapy and radiotherapy, new strategies for the treatment of PBTs are needed, especially for those with poor prognosis such as inoperable/difficult-to-reach lesions or relapsing disease. In regard to the last point, malignant primary brain tumors remain some of the most lethal types of cancer. Nuclear medicine may provide exciting new weapons and significant contributions in the treatment of PBTs. In this review, we performed literature research in order to highlight the possible role of peptide receptor radionuclide therapy (PRRT) in the treatment of PBTs with radiolabeled molecules that bind with high-affinity transmembrane receptors such as somatostatin receptors (SSTRs), neurokinin type-1 receptor and prostate-specific membrane antigen (PSMA). These receptors are overexpressed in some cancer types such as gliomas, meningiomas, pituitary tumors and medulloblastomas. A comprehensive overview of possible applications in this field will be shown, providing knowledge about benefits, feasibility, developments and limitations of PRRT in this type of tumor, also revealing new advantages in the management of the disease.

131I Uptake in Bronchiectasis Detected by Single Photon Emission Computed Tomography/Computed Tomography during Follow-up of Thyroid Cancer.

During follow-up of thyroid cancer, 131I whole-body scan showed intense tracer uptake in the right hemithorax of a patient previously submitted to thyroidectomy and radioiodine therapy for differentiated thyroid cancer. Thyroglobulin was undetectable at the time of the scan. Single-photon emission computed tomography/computed tomography (SPECT/CT) of the thorax correctly identified widespread bronchiectasis 131I-avid in the middle lobe of the right lung. After bronchoalveolar lavage, a bronchial specimen was positive for Mycobacterium avium infection. Hybrid imaging with SPECT/CT allowed to correctly identify a false-positive case of 131I uptake due to inflammation in a single diagnostic session, minimizing patient discomfort or misdiagnoses.

68Ga/64Cu PSMA Bio-Distribution in Prostate Cancer Patients: Potential Pitfalls for Different Tracers.

BACKGROUND: 68Ga-PSMA is a widely useful PET/CT tracer for prostate cancer imaging. Being a transmembrane protein acting as a glutamate carboxypeptidase enzyme, PSMA is highly expressed in prostate cancer cells. PSMA can also be labeled with 64Cu, offering a longer half-life and different resolution imaging. Several studies documented bio-distribution and pitfalls of 68Ga-PSMA as well as of 64Cu- PSMA. No data are reported on differences between these two variants of PSMA. Our aim was to evaluate physiological distribution of these two tracers and to analyze false positive cases. METHODS: We examined tracer bio-distribution in prostate cancer patients with negative 68Ga-PSMA PET/CT (n=20) and negative 64Ga-PSMA PET/CT (n=10). A diagnostic pitfall for each tracer was documented. RESULT: Bio-distribution of both tracers was similar, with some differences due to renal excretion of 68Ga- PSMA and biliary excretion of 64Cu-PSMA. 68Ga-PSMA uptake was observed in sarcoidosis while 64Cu- PSMA uptake was recorded in pneumonitis. DISCUSSION: Both tracers may present similar bio-distribution in the human body, with similar uptake in exocrine glands and high intestinal uptake. Similarly to other tracers, false positive cases cannot be excluded in clinical practice. CONCLUSION: The knowledge of difference in bio-distribution between two tracers may help in interpretation of PET data. Diagnostic pitfalls can be documented, due to the possibility of PSMA uptake in inflammation. Our results are preliminary to future studies comparing diagnostic accuracies of 68Ga-PSMA and 64Cu-PSMA.

Situs Inversus Totalis and Cholangiocarcinoma of the Gallbladder Detected by 18F-FDG PET/CT.

A 72-year-old woman was examined by F-FDG PET/CT, showing pathologic tracer uptake in the gallbladder. PET/CT also depicted condition of situs inversus totalis, with dextrocardia, liver on the left side and spleen on the right side of the body. These findings were essential to plan and develop laparoscopic cholecystectomy, which diagnosed cholangiocarcinoma. The recognition of anatomical variants and abnormalities by means of hybrid PET/CT imaging is essential in order to plan the best therapeutic approach.

Iodine-123 metaiodobenzylguanidine scintigraphy and iodine-123 ioflupane single photon emission computed tomography in Lewy body diseases: complementary or alternative techniques?

PURPOSE: To compare myocardial sympathetic imaging using (123)I-Metaiodobenzylguanidine (MIBG) scintigraphy and striatal dopaminergic imaging using (123)I-Ioflupane (FP-CIT) single photon emission computed tomography (SPECT) in patients with suspected Lewy body diseases (LBD). METHODS: Ninety-nine patients who performed both methods within 2 months for differential diagnosis between Parkinson's disease (PD) and other parkinsonism (n = 68) or between dementia with Lewy bodies (DLB) and other dementia (n = 31) were enrolled. Sensitivity, specificity, accuracy, positive and negative predictive values of both methods were calculated. RESULTS: For (123) I-MIBG scintigraphy, the overall sensitivity, specificity, accuracy, positive and negative predictive values in LBD were 83%, 79%, 82%, 86%, and 76%, respectively. For (123)I-FP-CIT SPECT, the overall sensitivity, specificity, accuracy, positive and negative predictive values in LBD were 93%, 41%, 73%, 71%, and 80%, respectively. There was a statistically significant difference between these two methods in patients without LBD, but not in patients with LBD. CONCLUSIONS: LBD usually present both myocardial sympathetic and striatal dopaminergic impairments. (123)I-FP-CIT SPECT presents high sensitivity in the diagnosis of LBD; (123)I-MIBG scintigraphy may have a complementary role in differential diagnosis between PD and other parkinsonism. These scintigraphic methods showed similar diagnostic accuracy in differential diagnosis between DLB and other dementia.

Cardiac adrenergic nerve function in patients with cardiac syndrome X.

BACKGROUND: We previously found a severe impairment of cardiac uptake of I-metaiodobenzylguanidine (MIBG), an analogue of norepinephrine, on myocardial scintigraphy in a small group of patients with cardiac syndrome X (CSX), suggesting a dysfunction of cardiac adrenergic nerve fibres. In this study, we assessed the consistency of these previous findings in a larger group of these patients. METHODS: Planar and single-photon emission computed tomography MIBG myocardial scintigraphy was performed in 40 CSX patients (58 +/- 7 years, 17 men). Cardiac MIBG uptake was measured by the heart/mediastinum ratio and by a single-photon emission computed tomography regional cardiac MIBG uptake defect score (higher values = lower uptake). As a control group, we studied 20 healthy individuals (56 +/- 6 years, nine men). An exercise stress Tc-SestaMIBI myocardial scintigraphy was performed in 34 CSX patients (85%). RESULTS: Cardiac MIBG defects were observed in 30 patients (75%), with nine (22.5%) showing no cardiac MIBG uptake at all. Compared with controls, CSX patients showed a significantly lower heart/mediastinum ratio (1.70 +/- 0.35 vs. 2.1 +/- 0.22, P < 0.001) and a higher cardiac MIBG defect score (27 +/- 25 vs. 4.4 +/- 2.5, P < 0.001). No differences were found in lung MIBG uptake between the two groups. Reversible perfusion defects on stress myocardial scintigraphy were found in 17 out of 34 CSX patients (50%), all of whom also had abnormal cardiac MIBG uptake; cardiac MIBG uptake abnormalities were also present in nine of 17 patients with normal perfusion scintigraphic images. Cardiac MIBG uptake findings were similar in our first 12 patients and in the 28 patients studied subsequently. CONCLUSION: Our data show a relevant impairment of cardiac MIBG uptake in patients with CSX, suggesting that functional abnormalities in cardiac adrenergic nerve function may play a significant role in the mechanisms responsible for the syndrome.

Myocardial (123)I-MIBG scintigraphy for differentiation of Lewy bodies disease from FTD.

Clinical distinction between Lewy bodies disease (LBD) and frontotemporal dementia (FTD) is sometimes difficult. Nigrostriatal dopaminergic degeneration occurs in both LBD and FTD, limiting helpfulness of DAT imaging to differentiate these forms of dementia. Several studies have emphasized the usefulness of myocardial scintigraphy with (123)Metaiodobenzylguanidine ((123)I-MIGB) in assessing the sympathetic nerve terminals in LBD demonstrating that cardiac (123)I-MIGB uptake is decreased in patients with this disease. We investigated the role of cardiac (123)I-MIBG scintigraphy in differentiating patients with LBD from those with FTD. Clinical diagnosis of LBD and FTD was determined according to established consensus criteria. Nine patients with LBD (1 possible and 8 probable), 6 patients with FTD, and 16 control subjects were involved in the study. The heart to mediastinum ratio (H/M) of (123)I-MIBG uptake was markedly reduced in all patients with LBD (H/M early: 1.25±0.12; delayed: 1.14±0.13) whereas it was normal in patients with FTD (H/M early: 1.86±0.20; delayed: 1.80±0.23) and in controls (H/M early: 1.91±0.17; delayed: 1.99±0.19), suggesting that cardiac (123)I-MIBG scintigraphy can help distinguish patients with LBD from those with FTD.

Combined use of DAT-SPECT and cardiac MIBG scintigraphy in mixed tremors.

The cooccurrence of rest and postural tremor (mixed tremor) as the predominant clinical manifestation in patients who do not fulfill diagnostic established criteria for essential tremor (ET) or Parkinson's disease (PD) poses a clinical diagnostic challenge. Twenty-two patients with mixed tremor and additional mild extrapyramidal features, such as bradykinesia and rigidity, 20 patients with probable PD, 10 patients with probable ET, and 18 controls were investigated through the combined use of dopamine transporter (123)I-FP-CIT-single-photon emission tomography (DAT-SPECT) and cardiac (123)metaiodobenzylguanidine (MIGB) scintigraphy. Six of the 22 mixed-tremor patients had normal DAT-SPECT, a condition usually found in patients with ET, whereas 16 patients showed damage to the nigrostriatal system. Cardiac MIBG allowed further differentiation between these 16 patients because eight of them had decreased tracer uptakes (heart/mediastinum [H/M] ratio in delayed image, H/M ratio delayed: 1.16 +/- 0.11, P < 0.001 vs controls), indicating a PD, whereas the remaining eight had normal cardiac tracer uptakes, a finding suggestive of a parkinsonian syndrome (H/M ratio delayed: 1.90 +/- 0.13). Both DAT-SPECT and cardiac MIBG scintigraphies were abnormal in the 20 patients with probable PD, whereas these were normal in both the patients with probable ET as well as in the controls. Our study suggests that the combined use of both DAT-SPECT and MIBG scintigraphy in mixed tremors with additional extrapyramidal features can help distinguish patients with ET from those with PD and parkinsonism.

Cardiac MIBG scintigraphy in Primary Progressive Freezing Gait.

Freezing of gait (FOG) generally occurs as a late manifestation of Parkinson's Disease (PD). FOG, however, can present in isolation, constituting the so-called "Primary Progressive Freezing Gait"(PPFG). Myocardial (123)Metaiodiobenzylguanidine (MIBG) enables the assessment of postganglionic sympathetic cardiac nerve terminals. MIBG uptake reflects sympathetic system integrity, and reduced myocardial uptake of the tracer has been observed in nearly all patients with PD. We investigated MIBG uptake in 7 patients with PPFG, 14 patients with mild PD, and 6 patients with advanced PD and FOG (PD-FOG), and 18 control subjects. Our study shows that myocardial MIBG uptake was normal in all patients with PPFG (H/M ratio: mean+/-SD, 1.85+/-0.11 early; 1.71+/-0.15 delayed) and in the controls (H/M ratio: mean+/-SD, 1.94+/-0.18 early; 2.02+/-0.19 delayed) whereas it was markedly decreased in the patients with mild and advanced PD (H/M ratio: mean+/-SD, PD: 1.17+/-0.02 early; 1.16+/-0.02 delayed; PD-FOG: 1.22+/-0.10 early; 1.08+/-0.06 delayed). Our findings demonstrate that cardiac sympathetic denervation did not occur in patients with PPFG, confirming that PPFG and PD are distinct diseases.

Myocardial 123metaiodobenzylguanidine uptake in genetic Parkinson's disease.

Myocardial (123)Metaiodobenzylguanidine (MIBG) enables the assessment of postganglionic sympathetic cardiac innervation. MIBG uptake is decreased in nearly all patients with Parkinson's disease (PD). Our objective was to evaluate MIBG uptake in patients with genetic PD. We investigated MIBG uptake in 14 patients with PD associated with mutations in different genes (Parkin, DJ-1, PINK1, and leucine-rich repeat kinase 2 -LRRK2), in 15 patients with idiopathic PD, and 10 control subjects. The myocardial MIGB uptake was preserved in 3 of the 4 Parkin-associated Parkinsonisms, in 1 of the 2 patients with DJ-1 mutations, in 1 of the 2 brothers with PINK1 mutations, in 3 of the 6 unrelated patients with Gly2019Ser mutation in the LRRK2 gene, whereas it was impaired in all patients with idiopathic PD. MIBG was preserved in all control subjects. Our study shows that myocardial MIGB uptake was normal in 8 of 14 patients with genetic PD, suggesting that cardiac sympathetic denervation occurs less frequently in genetic PD than in idiopathic PD. Our findings also demonstrate that MIGB uptake has a heterogeneous pattern in genetic PD, because it was differently impaired in patients with different mutations in the same gene or with the same gene mutation.