Diagnostic performance of [68Ga]DOTATATE PET/CT, [18F]FDG PET/CT, MRI of the spine, and whole-body diagnostic CT and MRI in the detection of spinal bone metastases associated with pheochromocytoma and paraganglioma.

OBJECTIVE: To compare the diagnostic performance of [68Ga]DOTATATE PET/CT, [18F]FDG PET/CT, MRI of the spine, and whole-body CT and MRI for the detection of pheochromocytoma/paraganglioma (PPGL)-related spinal bone metastases. MATERIALS AND METHODS: Between 2014 and 2020, PPGL participants with spinal bone metastases prospectively underwent [68Ga]DOTATATE PET/CT, [18F]FDG PET/CT, MRI of the cervical-thoracolumbar spine (MRIspine), contrast-enhanced MRI of the neck and thoraco-abdominopelvic regions (MRIWB), and contrast-enhanced CT of the neck and thoraco-abdominopelvic regions (CTWB). Per-patient and per-lesion detection rates were calculated. Counting of spinal bone metastases was limited to a maximum of one lesion per vertebrae. A composite of all functional and anatomic imaging served as an imaging comparator. The McNemar test compared detection rates between the scans. Two-sided p values were reported. RESULTS: Forty-three consecutive participants (mean age, 41.7 ± 15.7 years; females, 22) with MRIspine were included who also underwent [68Ga]DOTATATE PET/CT (n = 43), [18F]FDG PET/CT (n = 43), MRIWB (n = 24), and CTWB (n = 33). Forty-one of 43 participants were positive for spinal bone metastases, with 382 lesions on the imaging comparator. [68Ga]DOTATATE PET/CT demonstrated a per-lesion detection rate of 377/382 (98.7%) which was superior compared to [18F]FDG (72.0%, 275/382, p < 0.001), MRIspine (80.6%, 308/382, p < 0.001), MRIWB (55.3%, 136/246, p < 0.001), and CTWB (44.8%, 132/295, p < 0.001). The per-patient detection rate of [68Ga]DOTATATE PET/CT was 41/41 (100%) which was higher compared to [18F]FDG PET/CT (90.2%, 37/41, p = 0.13), MRIspine (97.6%, 40/41, p = 1.00), MRIWB (95.7%, 22/23, p = 1.00), and CTWB (81.8%, 27/33, p = 0.03). CONCLUSIONS: [68Ga]DOTATATE PET/CT should be the modality of choice in PPGL-related spinal bone metastases due to its superior detection rate. CLINICAL RELEVANCE STATEMENT: In a prospective study of 43 pheochromocytoma/paraganglioma participants with spinal bone metastases, [68Ga]DOTATATE PET/CT had a superior per-lesion detection rate of 98.7% (377/382), compared to [18F]FDG PET/CT (p < 0.001), MRI of the spine (p < 0.001), whole-body CT (p < 0.001), and whole-body MRI (p < 0.001). KEY POINTS: • Data regarding head-to-head comparison between functional and anatomic imaging modalities to detect spinal bone metastases in pheochromocytoma/paraganglioma are limited. • [68Ga]DOTATATE PET/CT had a superior per-lesion detection rate of 98.7% in the detection of spinal bone metastases associated with pheochromocytoma/paraganglioma compared to other imaging modalities: [18]F-FDG PET/CT, MRI of the spine, whole-body CT, and whole-body MRI. • [68Ga]DOTATATE PET/CT should be the modality of choice in the evaluation of spinal bone metastases associated with pheochromocytoma/paraganglioma.

International consensus on the use of tau PET imaging agent 18F-flortaucipir in Alzheimer's disease.

PURPOSE: Positron emission tomography (PET) with the first and only tau targeting radiotracer of 18F-flortaucipir approved by FDA has been increasingly used in depicting tau pathology deposition and distribution in patients with cognitive impairment. The goal of this international consensus is to help nuclear medicine practitioners procedurally perform 18F-flortaucipir PET imaging. METHOD: A multidisciplinary task group formed by experts from various countries discussed and approved the consensus for 18F-flortaucipir PET imaging in Alzheimer's disease (AD), focusing on clinical scenarios, patient preparation, and administered activities, as well as image acquisition, processing, interpretation, and reporting. CONCLUSION: This international consensus and practice guideline will help to promote the standardized use of 18F-flortaucipir PET in patients with AD. It will become an international standard for this purpose in clinical practice.

International consensus on the use of [18F]-FDG PET/CT in pediatric patients affected by epilepsy.

PURPOSE: Positron emission tomography (PET) with 18F-fluorodeoxyglucose ([18F]-FDG) has been increasingly applied in precise localization of epileptogenic focus in epilepsy patients, including pediatric patients. The aim of this international consensus is to provide the guideline and specific considerations for [18F]-FDG PET in pediatric patients affected by epilepsy. METHODS: An international, multidisciplinary task group is formed, and the guideline for brain [18F]-FDG PET/CT in pediatric epilepsy patients has been discussed and approved, which include but not limited to the clinical indications, patient preparation, radiopharmaceuticals and administered activities, image acquisition, image processing, image interpretation, documentation and reporting, etc. CONCLUSION: This is the first international consensus and practice guideline for brain [18F]-FDG PET/CT in pediatric epilepsy patients. It will be an international standard for this purpose in clinical practice.

The application of 18F-FDG PET/CT imaging for human hepatocellular carcinoma: a narrative review.

Background and Objective: Primary hepatocellular carcinoma (HCC) poses a significant threat to human health. The mean overall survival (OS) of HCC is approximately 15.8 months whereas the 6-month and 1-year OS rates are only 71.6% and 49.7%, respectively. 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) has been widely used for the management of several solid cancers; however, HCC frequently displays low 18F-FDG uptake; approximately 50% of HCC cases do not take up 18F-FDG. Therefore, 18F-FDG PET is not considered very useful for the visualization of HCC and is not currently a recommended standard imaging modality for HCC. Conversely, 18F-FDG PET/CT has been reported to be clinically important in the management, staging, and prognosis of HCC patients. Currently, reports relating to 18F-FDG uptake in HCC are unclear and controversial. There is an urgent need to clarify the efficacy of 18F-FDG PET for the management of HCC. Methods: The PubMed database was searched for all articles on the application of 18F-FDG PET/CT imaging for human HCC up to December 2021. The following search terms were used: 'Hepatocellular carcinoma', '[18F]FDG PET/CT', 'Hypoxia', '[11C]Choline'. Key Content and Findings: In this review, we re-evaluate the potential hypoxia-dependent uptake mechanism of 18F-FDG in HCC and review the usefulness of 18F-FDG PET/CT for identifying, managing, and investigating the biological properties of HCC. Conclusions: 18F-FDG PET/CT is very useful for HCC visualization, management, and the evaluation of biological properties. A negative test for 18F-FDG uptake is not meaningless and may reflect a relatively better outcome. 18F-FDG-positive lesions indicate a significantly less favorable prognosis.

Likely Common Role of Hypoxia in Driving 18F-FDG Uptake in Cancer, Myocardial Ischemia, Inflammation and Infection.

First introduced in 1976, 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) has become an indispensable tool for diagnosis and prognostic evaluation of tumors, heart disease, as well as other conditions, including inflammation and infection. Because 18F-FDG can accurately reflect the glucose metabolism level of organs and tissues, it is known as a "century molecule" and is currently the main agent for PET imaging. The degree of 18F-FDG uptake by cells is related to both the rate of glucose metabolism and glucose transporter expression. These, in turn, are strongly influenced by hypoxia, in which cells meet their energy needs through glycolysis, and 18F-FDG uptake increased due to hypoxia. 18F-FDG uptake is a complex process, and hypoxia may be one of the fundamental driving forces. The correct interpretation of 18F-FDG uptake in PET imaging can help clinics make treatment decisions more accurately and effectively. In this article, we review the application of 18F-FDG PET in tumors, myocardium, and inflammation. We discuss the relationship between 18F-FDG uptake and hypoxia, the possible mechanism of 18F-FDG uptake caused by hypoxia, and the associated clinical implications.

Tc-99m sestamibi uptake in the chest mimicking a malignant lesion of the breast.

The use of nuclear medicine imaging of the breast has resulted in the improved diagnosis of breast cancer (Radiology 196 (1995) 421; J. Nucl. Med. 36 (1995) 1758). It's use is becoming more widespread, particularly as breast optimized scintigraphy with a high-resolution, breast-specific gamma camera has been developed (J. Nucl. Med. 43 (2002) 909; J. Nucl. Med. 45 (2004) 553). With the increasing use of breast-optimized scintigraphy, pitfalls in the interpretation of breast-optimized scintigraphy are being recognized. This report describes a previously unrecognized cause for a false positive interpretation of scintimammography due to tumor uptake of the radiotracer in the chest as a result of physiologic activity in the auricular aspect of the right atrium.

Cutaneous metastatic lung cancer detected with 18F-FDG PET.

A 48-year-old male smoker presented with a chief complaint of persistent cough for three months. A CT scan revealed only a large right paratracheal mass. The plan was to obtain histological confirmation of suspected lung cancer via bronchoscopy and mediastinoscopy. A whole body 18F-FDG (2-deoxy-2-[18F]fluoro-D-glucose) PET Scan was ordered for staging and localization of the most accessible biopsy site. There was a large, intense hypermetabolic focus corresponding to the paratracheal lesion seen on CT, as well as a lesion in the right adrenal gland. There was also a superficial, subcutaneous hypermetabolic lesion in the mid-back. The subcutaneous lesion, which previously had not been noted, was biopsied and proved to be metastatic adenocarcinoma consistent with the lung primary. This case illustrates the clinical utility of reporting soft tissue abnormalities, which may provide an alternative, more readily accessible location for biopsy that is both safer and less expensive than bronchoscopy or mediastinoscopy.

Pigmented villonodular synovitis mimics metastases on fluorine 18 fluorodeoxyglucose position emission tomography-computed tomography.

Pigmented villonodular synovitis (PVNS) is a benign joint disease best characterized on magnetic resonance imaging (MRI). The role of fluorine 18 fluorodeoxyglucose ((18)F-FDG) position emission tomography-computed tomography (PET-CT) in the diagnosis or characterization remains unclear. PVNS displays as a focal FDG avid lesion, which can masquerade as a metastatic lesion, on PET-CET. We present a case of PVNS found on surveillance imaging of a lymphoma patient.

Prospective evaluation of delayed technetium-99m sestamibi SPECT scintigraphy for preoperative localization of primary hyperparathyroidism.

BACKGROUND: Delayed technetium-99m sestamibi single photon emission computed tomography (SPECT) scans were prospectively analyzed in a large series of patients with primary hyperparathyroidism. METHODS: Three hundred thirty-eight patients underwent sestamibi-SPECT and were explored. Prospective data included preoperative demographics, clinical, sestamibi, and operative findings, laboratory values, and pathologic and follow-up laboratory results from all patients. RESULTS: Between 1994 and 2000, 287 unexplored patients (85%) and 51 re-explored patients (15%) participated. The abnormal parathyroid glands excised from 336 of 338 patients included 299 single adenomas (88%) and 23 double adenomas (7%), and 14 patients had multigland hyperplasia (4%). Sestamibi SPECT correctly lateralized 349 of 400 abnormal parathyroid glands, with an overall sensitivity of 87%, an accuracy of 94%, and a positive predictive value of 86%. Precise localization occurred in 82% of the abnormal parathyroid glands. Sestamibi sensitivity was similar in unexplored (87%) and reoperative (92%) cases; two hundred eighty-six of 299 (96%) solitary adenomas, 38 of 46 (83%) double adenomas, but only 25 of 55 (45%) hyperplastic glands were identified. The mean weight of the true-positive glands (1252 +/- 1980 mg) was greater than that of the false-negative glands (297 +/- 286 mg) (P <.005). Three patients had persistent primary hyperparathyroidism, in spite of the excision of sestamibi-identified lesions in 2 cases. Follow-up indicated curative resection in 99% of the unexplored cases and 94% of the remedial cases. CONCLUSIONS: Sestamibi SPECT is highly accurate for the localization of parathyroid adenomas in unexplored and re-explored cases, where it is often the only imaging required. Its sensitivity is limited in multiglandular disease.

Effect of calcium channel blockers on the sensitivity of preoperative 99mTc-MIBI SPECT for hyperparathyroidism.

BACKGROUND: Technetium 99m ( 99m Tc)-methoxyisobutylisonitrile (MIBI) single photon emission computed tomography (SPECT) is frequently used in the evaluation of patients with hyperparathyroidism. Calcium channel blockers (CACBs) may affect 99m Tc-MIBI uptake by parathyroid cells. This study examines the effect of CACB therapy on the sensitivity of 99m Tc-MIBI SPECT localization for hyperparathyroidism. METHODS: Two hundred fifty-three operated patients with hyperparathyroidism were retrospectively reviewed. The potential effect of CACB therapy on 99m Tc-MIBI scan sensitivity was examined by using logistic regression analysis. Possible confounding factors were considered. RESULTS: Among 235 patients, those with multiple endocrine neoplasia, type I (MEN-I), MEN-IIA, 4-gland hyperplasia, secondary hyperparathyroidism, and tertiary hyperparathyroidism exhibited no difference associated with CACB use. Of the remaining 198 patients with primary hyperparathyroidism, 7/30 (23%) with negative 99m Tc-MIBI SPECT scans compared to 24/168 (14%) with positive scans used CACBs. After correcting for age, gender and gland weight, the odds ratio (OR) for a negative study in patients taking CACBs was 2.88 (95% CI, 1.03-8.10; P = .045). Atherosclerosis, hypertension, diabetes mellitus, preoperative calcium and parathyroid hormone levels, and thyroid hormone use were not confounding factors. CONCLUSIONS: CACB therapy reduces the sensitivity of 99m Tc-MIBI parathyroid SPECT in patients with primary hyperparathyroidism. Further studies are required to determine the potential reversibility of this effect with termination of CACB therapy.

Lung scan in the diagnosis and management of patent foramen ovale pulmonary embolism, paradoxical embolism.

This case illustrates the reopening of foramen ovale in a young patient with chronic pulmonary hypertension caused by bronchiectasis and chronic pulmonary fibrosis, which resulted in a prominent right-to-left shunt and severe hypoxia. Her clinically unsuspected right-to-left shunt was discovered during ventilation-perfusion scan, which was performed for the evaluation of pulmonary embolism. She had common variable immune deficiency, a primary immunodeficiency disease in which B-lymphocytes produce few or no antibodies. Most patients with this syndrome have an intrinsic defect in their B-lymphocytes that results in reduced immunoglobulin production. In these patients, recurrent respiratory tract infections are common and may result in chronic lung disease, fibrosis, particularly bronchiectasis (20-30%) and even cor pulmonale as happened in our patient [J. Clin. Immunol. 9 (1989) 22-33.].

Bisphosphonate-related osteonecrosis of the jaw mimicking bone metastasis.

Osteonecrosis of the jaw is usually a potential complication of bisphosphonate therapy. In a cancer patient, this disease entity can be misdiagnosed as a metastatic lesion. Our aim is to make clinicians aware of bisphosphonate associated osteonecrosis of the jaw to prevent misdiagnosis and initiate proper treatment at the earliest. We present the case of a breast cancer patient with multiple bony metastases and a jaw lesion presumed to be metastases. After no response to palliative radiation, repeat radiological imaging studies revealed osteonecrosis of the jaw. Correlating a patient's clinical information with findings on diagnostic imaging studies, such as SPECT bone and CT scans, can help identify this potential complication of bisphosphonate treatment. Early diagnosis helps minimize unnecessary biopsies and allows for the proper treatment to be instituted.

(18)F-fluorodeoxyglucose uptake and tumor hypoxia: revisit (18)f-fluorodeoxyglucose in oncology application.

UNLABELLED: This study revisited (18)F-fluorodeoxyglucose ((18)F-FDG) uptake and its relationship to hypoxia in various tumor models. METHODS: We generated peritoneal carcinomatosis and subcutaneous xenografts of colorectal cancer HT29, breast cancer MDA-MB-231, and non-small cell lung cancer A549 cell lines in nude mice. The partial oxygen pressure (pO2) of ascites fluid was measured. (18)F-FDG accumulation detected by digital autoradiography was related to tumor hypoxia visualized by pimonidazole binding and glucose transporter-1 (GLUT-1) in frozen tumor sections. RESULTS: Ascites pO2 was 0.90 ± 0.53 mm Hg. Single cancer cells and clusters suspended in ascites fluid as well as submillimeter serosal tumors stained positive for pimonidazole and GLUT-1 and had high (18)F-FDG uptake. In contrast, (18)F-FDG uptake was significantly lower in normoxic portion (little pimonidazole binding or GLUT-1 expression) of larger serosal tumors or subcutaneous xenografts, which was not statistically different from that in the liver. CONCLUSIONS: Glucose demand ((18)F-FDG uptake) in severely hypoxic ascites carcinomas and hypoxic portion of larger tumors is significantly higher than in normoxic cancer cells. Warburg effect originally obtained from Ehrlich ascites carcinoma may not apply to normoxic cancer cells. Our findings may benefit the better understanding of (18)F-FDG PET in oncology application.

Focus on China: should clinicians engage in research? and lessons from other countries.

Following tremendous economic progress, society in China is also undergoing fundamental changes, as is the healthcare system. Currently the training of Chinese young doctors and their future work placement are all undergoing re-structuring. We compiled some thoughts and opinions on the topic of 'should clinicians in China engage in research?', and publish them as a special report in this issue of Quantitative Imaging in Medicine and Surgery (QIMS). The contributors included some editorial members of this journal, and a few personal friends. Besides a few minor linguistic corrections, opinions from the contributors have not been edited, as we want authors' to write their own independent views. However, it is possible there is a selection bias of the contributors of this paper; more likely those who are interested in the medical research are selected and therefore the views of the contributors may not be generalizable. To compare the structure and funding of China with other countries, authors from UK, The Netherlands, France, and USA are also invited.

(18)F-misonidazole PET imaging of hypoxia in micrometastases and macroscopic xenografts of human non-small cell lung cancer: a correlation with autoradiography and histological findings.

The objective of this study was to determine whether (18)F-misonidazole could detect hypoxia in macroscopic and microscopic tumors in mice. In nude mice, subcutaneous xenografts and peritoneal metastases were generated utilizing human non-small cell lung cancer A549 and HTB177 cells. Animals were co-injected with (18)F-misonidazole, pimonidazole and bromodeoxyuridine, and tumor perfusion was assessed by Hoechst 33342 injection. The intratumoral distribution of (18)F-misonidazole was determined by micro-PET scan and autoradiography. Pimonidazole, bromodeoxyuridine and Hoechst 33342 were detected by immunohistochemistry on the autoradiography sections. Submillimeter micrometastases found to be severely hypoxic. In both peritoneal metastases and subcutaneous xenografts models, PET images displayed significant (18)F-misonidazole uptake, and its distribution was non-uniform in these macroscopic subcutaneous tumors. In frozen sections, digital autoradiography and immunohistochemistry revealed similar distributions of (18)F-misonidazole, pimonidazole and glucose transporter-1, in both microscopic and macroscopic tumors. Bromodeoxyuridine stained-positive proliferative regions were well perfused, as judged by Hoechst 33342, and displayed low (18)F-misonidazole accumulation. (18)F-misonidazole uptake was low in tumor stroma and necrotic zones as well. Microscopic non-small cell lung cancer metastases are severely hypoxic. (18)F-misonidazole PET is capable to image hypoxia noninvasively not only in macroscopic tumors but also in micrometastases growing in mice. Accordingly, (18)F-misonidazole may be a promising agent to detect the burden of micrometastatic diseases.