Rationale and design of the RAPID-WATER-FLOW trial: Radiolabeled perfusion to identify coronary artery disease using water to evaluate responses of myocardial FLOW.

OBJECTIVES: The objective of this study was to determine the diagnostic performance of 15O-water positron emission tomography (PET) myocardial perfusion imaging to detect coronary artery disease (CAD) using the truth-standard of invasive coronary angiography (ICA) with fractional flow reserve (FFR) or instantaneous wave-Free Ratio (iFR) or coronary computed tomography angiogram (CCTA). BACKGROUND: 15O-water has a very high first-pass extraction that allows accurate quantification of myocardial blood flow and detection of flow-limiting CAD. However, the need for an on-site cyclotron and lack of automated production at the point of care and relatively complex image analysis protocol has limited its clinical use to date. METHODS: The RAPID WATER FLOW study is an open-label, multicenter, prospective investigation of the accuracy of 15O-water PET to detect obstructive angiographic and physiologically significant stenosis in patients with suspected CAD. The study will include the use of an automated system for producing, dosing, and injecting 15O-water and enrolling approximately 215 individuals with suspected CAD at approximately 10 study sites in North America and Europe. The primary endpoint of the study is the diagnostic sensitivity and specificity of the 15O-water PET study using the truth-standard of ICA with FFR or iFR to determine flow-limiting stenosis, or CCTA to rule out CAD and incorporating a quantitative analytic platform developed for the 15O-water PET acquisitions. Sensitivity and specificity are to be considered positive if the lower bound of the 95% confidence interval is superior to the threshold of 60% for both, consistent with prior registration studies. Subgroup analyses include assessments of diagnostic sensitivity, specificity, and accuracy in female, obese, and diabetic individuals, as well as in those with multivessel disease. All enrolled individuals will be followed for adverse and serious adverse events for up to 32 hours after the index PET scan. The study will have >90% power (one-sided test, α = 0.025) to test the hypothesis that sensitivity and specificity of 15O-water PET are both >60%. CONCLUSIONS: The RAPID WATER FLOW study is a prospective, multicenter study to determine the diagnostic sensitivity and specificity of 15O-water PET as compared to ICA with FFR/iFR or CCTA. This study will introduce several novel aspects to imaging registration studies, including a more relevant truth standard incorporating invasive physiologic indexes, coronary CTA to qualify normal individuals for eligibility, and a more quantitative approach to image analysis than has been done in prior pivotal studies. CLINICAL TRIAL REGISTRATION INFORMATION: Clinical-Trials.gov (#NCT05134012).

Dural involvement in central nervous system langerhans cells histiocytosis (LCH) on FDG PET/CT: Case report and review of CNS manifestations of LCH on PET/CT.

We report a case of multisystem Langerhans cell histiocytosis in a pediatric patient with central nervous system involvement, highlighting F-18(FDG) uptake characteristics of dural sites of disease. We also highlight the advantages of functional data offered by FDG-PET as a useful follow-up tool to assess viability and, therefore, treatment response of previously known central nervous system lesions. The utility of recognizing characteristic patterns of FDG uptake in dural disease is also applicable in cases of diagnostic uncertainty, such as when evaluating isolated dural lesions or when distinguishing between Langerhans cell histiocytosis and similar appearing lesions such as meningiomas.

Nuclear Imaging of Neuroendocrine Tumors.

Consensus guidelines acknowledge the role of gallium Ga-68 (68Ga) 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic (DOTA) somatostatin receptor (SSTR) positron emission tomography/computed tomography (PET/CT) in management of neuroendocrine tumor (NET) patients. 68Ga-DOTA-SSTR PET/CT demonstrates superior performance to conventional imaging in initial detection, staging, detection of recurrent tumor, and detection of unknown primary in known metastatic disease. 68Ga-DOTA-SSTR PET/CT is low yield for NET detection in the setting of symptoms or elevated biomarkers when conventional imaging is negative, but may still guide management. The role of 68Ga-DOTA-SSTR PET/CT is not established in monitoring response to systemic therapy but may identify progression through detection of new metastases.

Chronic Venous Insufficiency Causing a Diagnostic Conundrum on Tc-99m Bone Scan Done for Osteosarcoma Surveillance: Awareness is the Key!

Bone scans are the most commonly used imaging technique to rule out local recurrence or metastasis during surveillance of malignant bone tumors after treatment. Although bone scans are very sensitive in detecting recurrence or metastasis, they are less specific. There are many nonmalignant conditions which can mimic either recurrence or metastasis on a Tc-99m bone scan. Therefore, physicians must be aware of such conditions to avoid unnecessary workup and invasive procedures. We present such an interesting case where chronic venous insufficiency mimicked either osteomyelitis or regional metastasis on a Tc-99m bone scan done for osteosarcoma surveillance.

Posterior Reversible Encephalopathy Syndrome on 18F-FDG PET/CT in a Pediatric Patient With Burkitt's Lymphoma.

We present a case of posterior reversible encephalopathy syndrome (PRES) in a pediatric patient with Burkitt's lymphoma predominantly involving the bone marrow. F-FDG PET/CT scan obtained after the first cycle of chemotherapy, complicated by acute kidney injury, hypertension, tumor lysis syndrome, and lethargy with focal neurological symptoms, showed a favorable marrow and lymph node response but increased FDG uptake in the bilateral frontal and occipital cortical/subcortical regions. Brain MRI was consistent with PRES. The patient was managed with IV hydration and blood pressure control with symptom resolution. This case shows the F-FDG uptake pattern of PRES in postchemotherapy setting.

Safety and accuracy of 68Ga-DOTATOC PET/CT in children and young adults with solid tumors.

68Ga-DOTA-tyr3-Octreotide (68Ga-DOTATOC) PET/CT has been shown to have high accuracy in adults with neuroendocrine tumors, however has not been studied in pediatric patients. This study evaluated the safety and accuracy of 68Ga-DOTATOC PET/CT in children and young adults with solid tumors that express somatostatin receptor type 2. A series of three prospective, IRB approved, clinical trials evaluating safety and efficacy of 68Ga-DOTATOC PET/CT were conducted for subjects aged 6 months to 90 years. This study reports the results for the 26 children and young adults, aged 16 months to 29 years who participated in these trials. The administered activity of 68Ga-DOTATOC was 1.59 MBq/kg with an upper limit of 111 MBq for subjects < 18 years and 148 MBq for young adults. Safety was assessed with laboratory studies and patient/parent report of symptoms before and after the scan. Scans were interpreted in consensus by two board-certified nuclear medicine physicians. Each scan was categorized on a patient basis as true positive, true negative, false negative or false positive against a reference standard that included a combination of histopathology, other imaging modalities and clinical follow-up. Nine Grade I adverse events (AEs) occurred among 26 subjects, none of which were attributable to 68Ga-DOTATOC. Sensitivity of 68Ga-DOTATOC PET/CT was 88% (14 true positive, 2 false negative) and specificity was 100% (10 true negative, 0 false positive). 68Ga-DOTATOC PET/CT is safe and accurate in children and young adults with solid tumors expressing somatostatin receptor type 2.

Sinonasal NUT-Midline Carcinoma - A Multimodality Approach to Diagnosis, Staging and Post-Surgical Restaging.

Nuclear protein testis (NUT) midline carcinoma is a rare malignancy involving predominantly the midline structures of the body. It is characterized by its genotypic feature of BRD4-NUT translocation, which is in contrast with other malignant processes that are usually categorized based on their histologic/phenotypic features. As these tumors may vary in their histologic presentation, they can be misdiagnosed as poorly differentiated carcinomas. Moreover, they are often very aggressive and associated with high mortality. Therefore, it is extremely important to diagnose them early using computed tomography (CT) and magnetic resonance imaging (MRI) and perform staging and restaging using 18-fluorodeoxyglucose positron emission tomography/computed tomography (18-FDG PET/CT), in addition to accurately identifying them at a microscopic and molecular level. We report a unique case of a sinonasal NUT midline carcinoma that was diagnosed with CT, staged with PET/CT, and restaged using PET/CT and MRI.

Incidental Meningioma Detected on 18F-Fluoride With PET/CT During Initial Staging for Prostate Cancer.

A 72-year-old man with recently diagnosed high-grade prostate adenocarcinoma with a Gleason score of 7 and PSA of 3.7 underwent ¹8F-fluoride PET/CT bone scan. The ¹8F-fluoride PET/CT bone scan showed increased uptake in the brain in the right frontal lobe. The follow-up MRI revealed a right frontal meningioma.