Musculoskeletal Pitfalls on Molecular Imaging Studies of Oncologic Patients: How to Stay Out of Trouble.

An increasing amount of molecular imaging studies are ordered each year for an oncologic population that continues to expand and increase in age. The importance of these studies in dictating further care for oncologic patients underscores the necessity of differentiating benign from malignant findings, particularly for a population in whom incidental findings are common. The aim of this review is to provide pictorial examples of benign musculoskeletal pathologies which may be found on molecular imaging and which may be mistaken for malignant processes. Imaging examples are provided in the form of radiographs, bone scintigraphy, computed tomography, and fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) scans. Special attention is paid to specific features that help narrow the differential diagnosis and distinguish benign from malignant processes, with the goal of avoiding unnecessary invasive procedures.

The Utility of PET/CT for the Diagnosis of Periosteal Chondrosarcoma in a Patient With Maffucci's Syndrome.

Maffucci's syndrome is a rare congenital nonhereditary syndrome with less than 300 cases having been reported in the United States. It is characterized by multiple enchondromas, hemangiomas, and rarely lymphangiomas. Enchondromas may undergo malignant transformation to chondrosarcomas. Surveillance plays a vital role in detecting early malignant transformation. Fluorodeoxyglucose (FDG) PET/CT, although falling out of favor, may be utilized as an imaging modality by physicians to determine such transformation, allowing for timely management and intervention. In this report, we share our experience with such a case.

Semantic intrusion errors are associated with plasma Ptau-181 among persons with amnestic mild cognitive impairment who are amyloid positive.

Introduction: Semantic intrusion errors (SI) have distinguished between those with amnestic Mild Cognitive Impairment (aMCI) who are amyloid positive (A+) versus negative (A-) on positron emission tomography (PET). Method: This study examines the association between SI and plasma - based biomarkers. One hundred and twenty-eight participants received SiMoA derived measures of plasma pTau-181, ratio of two amyloid-ß peptide fragments (Aß42/Aß40), Neurofilament Light protein (NfL), Glial Fibrillary Acidic Protein (GFAP), ApoE genotyping, and amyloid PET imaging. Results: The aMCI A+ (n = 42) group had a higher percentage of ApoE ɛ4 carriers, and greater levels of pTau-181 and SI, than Cognitively Unimpaired (CU) A- participants (n = 25). CU controls did not differ from aMCI A- (n = 61) on plasma biomarkers or ApoE genotype. Logistic regression indicated that ApoE ɛ4 positivity, pTau-181, and SI were independent differentiating predictors (Correct classification = 82.0%; Sensitivity = 71.4%; Specificity = 90.2%) in identifying A+ from A- aMCI cases. Discussion: A combination of plasma biomarkers, ApoE positivity and SI had high specificity in identifying A+ from A- aMCI cases.

Optimal timing of imaging in gastric emptying scintigraphy for the detection of delayed emptying.

OBJECTIVE: The purpose of this study was to evaluate a standard 4-h imaging protocol for gastric emptying scintigraphy (GES) in detecting delayed gastric emptying (GE). SUBJECTS AND METHODS: Gamma camera imaging was performed in the anterior and posterior views at 0, 0.5, 1, 1.5, 2, 2.5 and 4-h as per established Miami method (MIA) and National Standard Protocol (NSP), in accordance with the consensus guidelines of the ANMS/SNM [SNMMI] Societies. Patients (N=1002) received a standardized solid meal radiolabeled with 1mCi of technetium-99 (99mTc) sulfur colloid. Quantitative analysis was performed using geometric mean calculation of decay-corrected counts at each imaging time point, expressed as percent emptying or retention. RESULTS: In our patient cohort, 21% had delayed GE at 4h, whereas 79% had normal emptying with less than 10% retention at 4h. There was a 25% increase in delayed GE studies at 4h versus 2h. From those patients who had delayed GE at 2h, 30% normalized at 4h, while 10% of patients with normal GE at 2h became delayed at 4h thus indicating that more studies changed from abnormal to normal than from normal to abnormal at 4h. Greater than 90% GE was found in 9% of patients at 2 h and 25% of patients at 2.5h and this persisted at 4h. The study at 2h as compared with 4h, had 56% sensitivity, 95% specificity, 70% PPV and 91% NPV. CONCLUSION: The 4-h imaging was very important in detecting cases that were delayed at 2h but normalized at 4h, and also cases with normal GE at 2h that became abnormal at 4h. These findings support the ANMS/SNM [SNMMI] recommendations. Gastric emptying value ≥90% at 2.5h can be used as threshold in predicting normal GE and the study could be terminated without additional imaging.

Axitinib plus pembrolizumab in patients with advanced sarcomas including alveolar soft-part sarcoma: a single-centre, single-arm, phase 2 trial.

BACKGROUND: VEGF promotes an immunosuppressive microenvironment and contributes to immune checkpoint inhibitor resistance in cancer. We aimed to assess the activity of the VEGF receptor tyrosine-kinase inhibitor axitinib plus the anti-PD-1 immune checkpoint inhibitor pembrolizumab in patients with sarcoma. METHODS: This single-centre, single-arm, phase 2 trial was undertaken at a tertiary care academic medical centre in Miami, FL, USA, and participants were recruited from all over the USA and internationally. Patients were eligible if they were aged 16 years or older, and had histologically confirmed advanced or metastatic sarcomas, including alveolar soft-part sarcoma (ASPS); measurable disease with one site amenable to repeated biopsies; an ECOG performance status of 0-1; and progressive disease after previous treatment with at least one line of systemic therapy (unless no standard treatment existed or the patient declined therapy). The first five patients were enrolled in a lead-in cohort and were given axitinib 5 mg orally twice daily and pembrolizumab 200 mg intravenously for 30 min on day 8 and every 3 weeks for cycles of 6 weeks for up to 2 years. Thereafter, patients received escalating doses of axitinib (2-10 mg) plus flat dose pembrolizumab according to the schedule above. The primary endpoint was 3-month progression-free survival. All patients were evaluable for survival and safety analyses. This study is registered with ClinicalTrials.gov, number NCT02636725, and is closed to accrual. FINDINGS: Between April 19, 2016, and Feb 7, 2018, of 36 patients assessed for eligibility, 33 (92%) were enrolled and given study treatment (intention-to-treat population and safety population), 12 (36%) of whom had ASPS. With a median follow-up of 14·7 months (IQR 10·1-19·1), 3-month progression-free survival for all evaluable patients was 65·6% (95% CI 46·6-79·3). For patients with ASPS, 3-month progression-free survival was 72·7% (95% CI 37·1-90·3). The most common grade 3 or 4 treatment-related adverse events included hypertension (five [15%] of 33 patients), autoimmune toxicities (five [15%]), nausea or vomiting (two [6%]), and seizures (two [6%]). Serious treatment-related adverse events occurred in seven (21%) patients, including autoimmune colitis, transaminitis, pneumothorax, haemoptysis, seizures, and hypertriglyceridemia. There were no treatment-related deaths. INTERPRETATION: Axitinib plus pembrolizumab has manageable toxicity and preliminary activity in patients with advanced sarcomas, particularly patients with ASPS, warranting further investigation in randomised controlled trials. FUNDING: Merck, Pfizer, American Cancer Society, and Sylvester Comprehensive Cancer Center.

Renal scintigraphy in the acute care setting.

Renal scintigraphy is a powerful imaging method that provides both functional and anatomic information, which is particularly useful in the acute care setting. In our institution, for the past 2 decades, we have used a 25-minute renal diuretic protocol, technetium-99m ((99m)Tc) mercaptoacetyltriglycine with simultaneous intravenous injection of furosemide, for all ages and indications, including both native and transplant kidneys. As such, this protocol has been widely used in the workup of acutely ill patients. In this setting, there are common clinical entities which affect patients with native and transplant kidneys. In adult patients with native kidneys one of the most frequent reasons for emergency room visits is renal colic due to urolithiasis. Although unenhanced computed tomography is useful to assess the anatomy in cases of renal colic, it does not provide functional information. Time zero furosemide renal scintigraphy can do both and we have shown that it can effectively stratify patients with renal colic. To this end, 4 characteristic patterns of scintirenography have been identified, standardized, and consistently applied: no obstruction, partial obstruction (mild vs high grade), complete obstruction, and stunned (postdecompressed) kidney. With the extensive use of this protocol over the past 2 decades, a pattern of "regional parenchymal dysfunction" indicative of acute pyelonephritis has also been delineated. This information has proved to be useful for patients presenting with urinary tract infection and suspected pyelonephritis, as well as for patients who were referred for workup of renal colic but were found to have acute pyelonephritis instead. In instances of abdominal trauma, renal scintigraphy is uniquely suited to identify urine leaks. This is also true in cases of suspected leak following renal transplant or from other iatrogenic/postsurgical causes. Patients presenting with acute renal failure can be evaluated with renal scintigraphy. A scintigraphic pattern of "relative preservation of flow as compared to function" has been identified as indicative of acute tubular necrosis, which is distinct from other potential causes of acute renal failure, such as nephrotoxicity and in the case of renal transplants, rejection.

A renal protocol for all ages and all indications: mercapto-acetyl-triglycine (MAG3) with simultaneous injection of furosemide (MAG3-F0): a 17-year experience.

Current clinical requirements mandate the existence of a renal diuretic protocol, which is fast and easy, applicable in all ages and for all indications, convenient for both the patient and the technologist, and provides diagnostic as well as prognostic information. Seventeen years ago a 25-minute protocol, after oral hydration, with no bladder catheterization, and simultaneous injection of mercapto-acetyl-triglycine (MAG(3)) and furosemide (MAG(3)-F(0)), was initiated. It initially was used for the evaluation of drainage and emerged as a protocol to also evaluate the renal parenchyma. Results of this protocol have been published individually, per clinical application. MAG(3)-F(0) was instrumental in the evaluation and prognosis of congenital disorders. For obstruction, in the newborn, an increasing renogram mandates intervention, whereas a downsloping one predicts spontaneous resolution. In children or adults, preoperatively or postoperatively, when the cortex was visualized and drained normally, there was no obstruction, even if urine was retained within a dilated collecting system or an extrarenal pelvis. For diseases of the renal parenchyma, the protocol enabled the diagnosis of acute pyelonephritis (APN) revealing the "regional parenchymal dysfunction," diagnostic of APN. Diffuse parenchymal diseases were characterized by increased residual cortical activity (RCA), and their progression was manifested as a deterioration of RCA. End-stage renal disease was characterized by lack of accumulation and retention. Trauma and leaks were identified with specific patterns. In renovascular hypertension (RVH), an increase in RCA after angiotension-converting enzyme inhibitors is diagnostic of RVH and prognostic of the beneficial effect of angioplasty on hypertension. In renal colic, stratification was possible into (1) complete or severe obstruction requiring immediate intervention, (2) mild obstruction allowing waiting, (3) spontaneous decompression (stunned kidney), and (4) no recent obstruction. In transplants, it enabled differentiation of acute tubular necrosis, acute or chronic rejection and nephrotoxicity, and identified infarcts, RVH, leaks and obstruction. Finally, this method allows for a quick semiquantification of renal function. The clinical usefulness of the MAG(3)-F(0) protocol in most congenital or acquired renal problems is proven through long-term clinical experience and has resulted in a substantial utilization of the test at our Center.

The sodium-iodine symporter and the proton-pump inhibitors in - related to the side effects of- the treatment of thyroid cancer with iodine-131.

Iodine-131 ((131)I) administered to patients for imaging or treatment, concentrates in the gastrointestinal tract, including the salivary glands, stomach and bowel. In Nuclear Medicine practice this biological property of iodine causes side effects when the therapeutic dose of (131)I is large. This occurs during the treatment of patients with differentiated thyroid carcinoma (DTC). During this clinical application, the dose of (131)I is higher than 3.7 GBq. Side effects of this treatment with respect to the stomach, include gastritis as an inflammatory reaction to radiation, anorexia due to gastric atrophy and rarely megaloblastic anemia due to lack of the endogenous factor. Side effects can also include xerostomia. We have recently tried to prevent gastric side effects by prescribing proton pump inhibitors (PPI) for patients with DTC prior to treatment with (131)I. PPI block the excretion of hydrochloric acid from the gastric mucosa and are utilized for the prevention and treatment of gastritis, gastric ulcers and gastroesophageal reflux. Whole body scans before or after the administration of PPI, showed that PPI do not interfere with the biologic distribution of (131)I. These findings were not surprising. Recent studies in animals and humans have shown that the accumulation and concentration of iodine by the thyroid gland is the result of the selective action of sodium iodine symporter (Na+I+symporter, NIS). Furthermore, it was shown that the accumulation and concentration of (131)I in the parietal cells of the gastric mucosa, the ductal cells of the salivary glands and the alveolar epithelial cells of the mammary glands, is analogous to the biologic action of NIS in the thyroid cells. The gastric mucosa accumulates iodine from the capillaries via the extracellular/extravascular space and finally excretes it into the lumen of the stomach, from where it is passively transferred into the bowel, where it is partially reabsorbed to once again enter its metabolic cycle. On the contrary, as it is now known, the PPI have an entirely different metabolic action, which is unrelated to that of the NIS, although both mechanisms coexist in the parietal cells of the gastric mucosa. Thus, during the application of (131)I for imaging or for the treatment of DTC patients, except for the short period of time immediately after the oral administration, when the radionuclide passes through the stomach, the concentration of (131)I in the gastrointestinal tract is due to its active accumulation and excretion by the gastric mucosa. PPI act only on the hydrochloric acid secretion not affecting the biologic properties of iodine.