Common Skeletal Neoplasms and Nonneoplastic Lesions at 18F-FDG PET/CT.

Numerous primary and metastatic osseous lesions and incidental osseous findings are encountered at fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/CT. These lesions show varying degrees of FDG uptake. Malignancies are generally more FDG avid than are benign lesions, but many exceptions exist. Although aggressive lesions tend to be more FDG avid than nonaggressive lesions, this concept holds true particularly for lesions of the same histologic subtype. In addition, some benign osseous processes such as Paget disease have variable degrees of FDG avidity on the basis of disease metabolic activity. This creates a diagnostic dilemma for radiologists and clinicians, especially in patients with known malignancies, and can result in unnecessary diagnostic imaging or interventions for incidental osseous lesions. Evaluation of morphologic CT characteristics of osseous lesions at FDG PET/CT can be a valuable adjunct to metabolic analysis to further characterize lesions, enhance diagnostic and staging accuracy, and avoid unnecessary invasive biopsy procedures. The authors review the common primary and metastatic bone lesions at FDG PET/CT, with an emphasis on morphologic CT assessment of lesions to help narrow the differential diagnosis. Imaging manifestations of common incidental nonneoplastic bone lesions at FDG PET/CT are discussed to provide information on differentiation of these lesions from osseous neoplasms. The guidelines of the National Comprehensive Cancer Network (NCCN) for common primary osseous malignancies are also summarized. Online supplemental material is available for this article. ©RSNA, 2021.

Clinical Impact of FDG PET/CT of the Lower Extremities in Patients With Merkel Cell Carcinoma With Primary Disease Site Outside of the Lower Extremities.

OBJECTIVE. Whole-body imaging extending from the vertex of the head to the toes is considered the standard 18F-FDG PET/CT protocol for Merkel cell carcinoma, though the evidence establishing this standard is scant. The purpose of this study was to investigate the clinical impact of PET/CT of the lower extremities in patients with Merkel cell carcinoma, a rare aggressive neuroendocrine tumor of the skin. MATERIALS AND METHODS. A total of 101 patients with Merkel cell carcinoma (mean age, 70.9 years) who underwent whole-body PET/CT were included. PET/CT findings in the lower extremities were evaluated on a per-patient basis, and the results were compared between patients with the primary lesion in the lower extremities (lower extremity primary) and those with the primary lesion located between the head and inguinal regions (body primary). Subsequent clinical evaluation and follow-up imaging were used as the reference standard. RESULTS. In the lower extremity (n = 22) and body (n = 79) primary groups, five and eight patients had true metastases in the lower extremities (p = .15). In the body primary group, all metastases in the lower extremities were part of widespread metastases in the body. In contrast, three of five patients (60%) in the lower extremity primary group had isolated metastases in the lower extremities, which differed significantly from the rate in the body primary group (p = .04). Subgroup analysis that included 48 patients who underwent initial staging examinations showed no metastases in the lower extremities regardless of primary location. CONCLUSION. PET/CT of the lower extremities for patients with body primary lesions of Merkel cell carcinoma should be considered of limited clinical utility.

Mutations in Superoxide Dismutase 1 (Sod1) Linked to Familial Amyotrophic Lateral Sclerosis Can Disrupt High-Affinity Zinc-Binding Promoted by the Copper Chaperone for Sod1 (Ccs).

Zinc (II) ions (hereafter simplified as zinc) are important for the structural and functional activity of many proteins. For Cu, Zn superoxide dismutase (Sod1), zinc stabilizes the native structure of each Sod1 monomer, promotes homo-dimerization and plays an important role in activity by "softening" the active site so that copper cycling between Cu(I) and Cu(II) can rapidly occur. Previously, we have reported that binding of Sod1 by its copper chaperone (Ccs) stabilizes a conformation of Sod1 that promotes site-specific high-affinity zinc binding. While there are a multitude of Sod1 mutations linked to the familial form of amyotrophic lateral sclerosis (fALS), characterizations by multiple research groups have been unable to realize strong commonalities among mutants. Here, we examine a set of fALS-linked Sod1 mutations that have been well-characterized and are known to possess variation in their biophysical characteristics. The zinc affinities of these mutants are evaluated here for the first time and then compared with the previously established value for wild-type Sod1 zinc affinity. Ccs does not have the same ability to promote zinc binding to these mutants as it does for the wild-type version of Sod1. Our data provides a deeper look into how (non)productive Sod1 maturation by Ccs may link a diverse set of fALS-Sod1 mutations.

Long term follow-up of neoadjuvant chemotherapy for non-small cell lung cancer (NSCLC) investigating early positron emission tomography (PET) scan as a predictor of outcome.

BACKGROUND: Neoadjuvant chemotherapy is effective in improving survival of resectable NSCLC. Based on findings in the adjuvant and metastatic setting, FDG positron emission tomography (PET) scans may offer early prognostic or predictive value after one cycle of induction chemotherapy. METHODS: In this phase II non-randomized trial, patients with AJCC version 6 stage IB to IIIB operable NSCLC were treated with 3 cycles of cisplatin and pemetrexed neoadjuvant chemotherapy. Patients underwent FDG-PET scanning prior to and 18 to 21 days after the first cycle of chemotherapy. Investigators caring for patients were blinded to results, unless the scans showed evidence of disease progression. FDG-PET response was defined prospectively as a ≥ 20% decrease in the SUV of the primary lesion. RESULTS: Between October 2005 and February 2010, 25 patients enrolled. Fifty two percent were female, 88% white, and median age was 62 years. Histology was divided into adenocarcinoma 66%, not otherwise specified (NOS) 16%, squamous cell 12%, and large cell 4%. Stage distribution was: 16% IB, 4% IIB, and 79% IIIA. Treatment was well tolerated and only one patient had a grade 4 toxicity. The median follow up was 95 months. The 5 year progression free survival (PFS) and overall survival (OS) for the entire population were 54 and 67%, respectively. Eighteen patients had a baseline FDG-PET scan and a repeat scan at day 18-21 available for comparison. Ten patients (56%) were considered metabolic responders on the day 18-21 FDG-PET scan. Responders had a 5 year PFS and OS of 60 and 70%, respectively, while the percentage for non-responders was 63 and 75% (p = 0.96 and 0.85). CONCLUSIONS: This phase II trial did not demonstrate that a PET scan after one cycle of chemotherapy can predict survival outcomes of patients with NSCLC treated with neoadjuvant chemotherapy. TRIAL REGISTRATION: NCT00227539 registered September 28th, 2005.

Imaging of Merkel Cell Carcinoma: What Imaging Experts Should Know.

Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous neuroendocrine tumor with a higher mortality rate than melanoma. Approximately 40% of MCC patients have nodal or distant metastasis at initial presentation, and one-third of patients will develop distant metastatic disease over their clinical course. Although MCC is rare, its incidence has been steadily increasing. Furthermore, the immunogenicity of MCC and its diagnostic and therapeutic application have made MCC one of the most rapidly developing topics in dermatology and oncology. Owing to the aggressive and complex nature of MCC, a multidisciplinary approach is necessary for management of this tumor, including dermatologists, surgeons, radiation oncologists, medical oncologists, pathologists, radiologists, and nuclear medicine physicians. Imaging plays a crucial role in diagnosis, planning for surgery or radiation therapy, and assessment of treatment response and surveillance. However, MCC is still not well recognized among radiologists and nuclear medicine physicians, likely owing to its rarity. The purpose of this review is to raise awareness of MCC among imaging experts by describing the epidemiology, pathophysiology, and clinical features of MCC and current clinical management with a focus on the role of imaging. The authors highlight imaging findings characteristic of MCC, as well as the clinical significance of CT, MRI, sentinel lymph node mapping, fluorine 18 fluorodeoxyglucose PET/CT, and other nuclear medicine studies such as bone scintigraphy and somatostatin receptor scintigraphy. ©RSNA, 2019.

PET/CT in the Diagnosis and Workup of Sarcoidosis: Focus on Atypical Manifestations.

Sarcoidosis is a multisystem disease characterized by the formation of noncaseating granulomas. Lung and intrathoracic lymph nodes are classic sites of involvement; however, sarcoidosis can affect any site in the body. The clinical course is extremely variable, and the imaging features are diverse and dependent on the affected site, degree of inflammation, and treatment the patient receives. Atypical manifestations and imaging findings can make diagnosis and/or management challenging. In addition, assessment of treatment response can be difficult in the setting of chronic disease. Fluorine 18 fluorodeoxyglucose (FDG) PET/CT is sensitive for assessment of the inflammatory activity of sarcoidosis in any organ. Although FDG PET/CT is not included in the standard workup for sarcoidosis, there has been growing evidence that supports the value of this examination in guiding diagnosis and management. FDG PET/CT may be especially useful for assessing reversible granuloma, treatment response, disease extent, occult disease, and cardiac or osseous sarcoidosis, and determining the most suitable biopsy site. Capability to image the entire body during a single examination is advantageous in cases of systemic disease such as sarcoidosis. The authors review the use of FDG PET/CT, providing up-to-date evidence and describing various cases of sarcoidosis in which FDG PET/CT has an important role in diagnosis and/or management. They also discuss the usefulness of FDG PET/CT in cases of selective manifestations of sarcoidosis. ©RSNA, 2018.

Nuclear medicine and the emergency department patient: an illustrative case-based approach.

Radiologists are familiar with the use of radiographs, computed tomography, magnetic resonance imaging and ultrasound in the acute clinical setting. However, there are some specific clinical scenarios which may be found in nuclear medicine imaging problem-solving tools. These clinical scenarios and imaging techniques are less frequent, and the referring clinician from the emergency department may not consider these alternatives. It is important for the radiologist to be aware of these techniques to be able to guide the clinician to use those tools, which may result in optimal patient care. In this article, we will discuss those nuclear medicine studies which have application in the setting of an emergency radiology practice.

Newer PET application with an old tracer: role of 18F-NaF skeletal PET/CT in oncologic practice.

The skeleton is one of the most common sites for metastatic disease, particularly from breast and prostate cancer. Bone metastases are associated with considerable morbidity, and accurate imaging of the skeleton is important in determining the appropriate therapeutic plan. Sodium fluoride labeled with fluorine 18 (sodium fluoride F 18 [(18)F-NaF]) is a positron-emitting radiopharmaceutical first introduced several decades ago for skeletal imaging. (18)F-NaF was approved for clinical use as a positron emission tomographic (PET) agent by the U.S. Food and Drug Administration in 1972. The early use of this agent was limited, given the difficulties of imaging its high-energy photons on the available gamma cameras. For skeletal imaging, it was eventually replaced by technetium 99m ((99m)Tc)-labeled agents because of the technical limitations of (18)F-NaF. During the past several years, the widespread availability and implementation of hybrid PET and computed tomographic (CT) dual-modality systems (PET/CT) have encouraged a renewed interest in (18)F-NaF PET/CT for routine clinical use in bone imaging. Because current PET/CT systems offer high sensitivity and spatial resolution, the use of (18)F-NaF has been reevaluated for the detection of malignant and nonmalignant osseous disease. Growing evidence suggests that (18)F-NaF PET/CT provides increased sensitivity and specificity in the detection of bone metastases. Furthermore, the favorable pharmacokinetics of (18)F-NaF, combined with the superior imaging characteristics of PET/CT, supports the routine clinical use of (18)F-NaF PET/CT for oncologic imaging for skeletal metastases. In this article, a review of the indications, imaging appearances, and utility of (18)F-NaF PET/CT in the evaluation of skeletal disease is provided, with an emphasis on oncologic imaging.

Testicular FDG Uptake on PET/CT in Patients with Lymphoma: Correlation with Age.

The purpose of this observational study was to investigate whether the standard uptake value (SUV) measurement has practical utility in distinguishing secondary testicular involvement from physiologic uptake in patients with lymphoma. A Radiology Information System (RIS) search was conducted for all PET/CT studies performed from 2010-2016 on adult male patients with a diagnosis of lymphoma. Patients with clinical or pathologic diagnosis of testicular lymphoma were excluded to undergo a separate analysis. PET/CT images of 606 patients with 1087 scans, in which 2045 testes were included in the field of view, were reviewed and measurements were performed for standardized uptake values of both testicles (SUVmax) as well as of the liver (SUVmax and SUVmean). The mean SUVmax of the testicles was 3.75 ± 0.90 (range 1.16-8.38). The mean ratio of testis SUVmax / liver SUVmean (T/L) was 1.78 ± 0.43. Trends in SUVmax and age were significant for a negative correlation by a small magnitude of 0.066 per 10 years (P < 0.001). T/L had similar changes with significant low magnitude decrease with increasing age (0.059 per 10-year increase, P < 0.001). In our separate analysis of 3 patients with clinical or pathology proven testicular lymphoma, the average pathologic SUVmax was 13.47 (range 11.39-15.97). This study has the largest known sample size for quantifying physiologic uptake in the testes. SUV measurements to quantify F-18 Fluorodeoxyglucose (FDG) uptake on PET/CT likely have practical utility in discriminating between physiologic and pathologic uptake of FDG in cases of secondary testicular lymphoma.

A case of multiple aggressive osseous hemangiomas on bone scan.

A 49-year-old male with worsening back and right leg pain was referred for bone scan imaging. Bone scan demonstrated multifocal expansile osteoblastic bony lesions, atypical for benign osseous hemangiomas, which are commonly cold on bone scan. Multisite bone biopsies were compatible with the diagnosis of multifocal osseous hemangiomas. This case illustrates that aggressive osseous hemangiomas, a rare subtype of hemangiomas, may have variable osteoblastic activity on bone scan, ranging from mild to severe uptake.

Multimodality imaging evaluation for iliac crest apophysis avulsion injury.

A young cross-country athlete with left thigh pain, and a recent negative MRI of the left hip was referred to nuclear medicine for bone scan imaging. A 3-phase Tc-99m methylene diphosphonate bone scan was performed and revealed left iliac crest apophysis avulsion. This case illustrates that 3-phase bone scan is a great adjunct in the evaluation of sports injuries especially in athletes presenting with vague nonlocalizing symptoms, and prior negative radiographic or MRI imaging.

Spontaneous regression of a metastatic melanoma pulmonary deposit following biopsy.

Spontaneous complete and partial regression of metastatic melanoma is poorly understood, and is a rare phenomenon with less than 80 cases reported since 1866. Several correlations have been noted such as systemic or local infections, operative trauma, hormonal influences, nutrition and immunologic factors. We present FDG PET and CT findings in a patient with multiple pulmonary metastases of melanoma, one of which underwent regression following biopsy. We suggest immune system modulation, triggered by biopsy, could have played a role, although the precise mechanism remains unknown.

18F-Fluciclovine Uptake by an Incidentally Detected Hepatocellular Carcinoma in a Case of Biochemically Recurrent Prostate Cancer.

Prostate cancer is one of the most common cancers affecting men worldwide with a high recurrence rate following therapy. F-fluciclovine, is a US Food and Drug Administration-approved radiopharmaceutical for PET imaging in biochemically recurrent prostate cancer. It targets increased amino acid transporters in the cell membrane of cancer cells. We report a case of incidentally detected hepatocellular carcinoma showing F-fluciclovine uptake in a 71-year-old man with biochemically recurrent prostate cancer.

Lacrimal gland uptake on F-18 florbetapir amyloid positron emission tomography scan.

In 2012, the Food and Drug Administration (FDA) approved the use of F-18 florbetapir to estimate ß-amyloid neuritic plaque density when indicated. A normal scan will show increased radiotracer uptake in the white matter. Mild uptake in salivary glands, skin, muscles, and bones is considered normal. Being a new and infrequently performed study, familiarity with normal biodistribution and variants is important. We hereby present 2 cases with F-18 florbetapir uptake in lacrimal glands. Patients had no symptoms or known systemic conditions to explain this uptake. We speculate that lacrimal gland uptake of F-18 florbetapir could represent a normal variant.

Hepatopulmonary shunting on Tc99m-MAA liver mapping: correlation with dynamic cross-sectional imaging and description of different shunting patterns.

PURPOSE: The purpose of the study was to correlate lung shunt fraction (LSF) calculated by intra-arterial injection of Technetium-99m (Tc-99m)-labeled macroaggregated albumin (MAA) in a hepatic artery branch with the presence of certain patterns of vascular shunts on dynamic CT or MRI of the liver. METHODS: This retrospective study was approved by the institutional review board and informed consent was waived. We reviewed 523 MAA scans in 453 patients (301 men, 152 women) performed from July 2007 to June 2015 and their correlative cross-sectional imaging. Patterns of vascular shunts on dynamic CT or MRI performed within 3 months of the MAA study and that potentially divert hepatic arterial inflow to the systemic venous return were defined as "target shunts." Dynamic CT or MRI was classified into three groups with target shunt present, absent, or indeterminate. The mean LSF was compared across the first and second groups using paired t test. RESULTS: 342 CT and MRI studies met inclusion criteria: target shunts were present in 63 studies, absent in 271 studies, and 8 studies were indeterminate. When target shunts were visualized, the mean LSF on corresponding MAA scans was 12.9 ± 10.36% (95% CI 10.29-15.15%) compared to 4.3 ± 3.17% (95% CI 3.93-4.68%) when no target shunt was visualized. The difference was statistically significant (p value < 0.001). Identified target shunts were either direct (arteriohepatic venous shunt) or indirect (arterioportal shunt combined with a portosystemic shunt). CONCLUSIONS: Visualizing certain patterns of vascular shunting on a dynamic CT or MRI scan is associated with high LSF.

Biliary Leak in the Postsurgical Abdomen: A Primer to HIDA Scan Interpretation.

Postsurgical bile leaks can be associated with significant morbidity and even mortality, if not identified and treated at an early phase. Hepatobiliary iminodiacetic acid (HIDA) scan is an important test for detection of bile leaks in the postoperative abdomen. However, the lack of anatomical details on planar images can make interpretation difficult, especially in the setting of altered postsurgical anatomy. Familiarity with the expected postoperative appearance on HIDA scan and correlation with SPECT/CT or other imaging modalities when available are very important. The purpose of this review is to describe the expected findings on HIDA scan after common major abdominal surgeries that involve a change in biliary tree anatomy, and illustrate how to identify biliary leaks and avoid interpretation pitfalls.

A Case of Nasal Merkel Cell Carcinoma Draining to a Buccinator Sentinel Lymph Node.

A 73-year-old man diagnosed with Merkel cell carcinoma of the left nasal ala was referred for preoperative scintigraphic sentinel lymph node mapping. In three separate foci around the lesion, 0.2 mCi of Tc-sulfur colloid was intradermally administered. Planar images demonstrated accumulation of tracer midway between the nose and left ear. SPECT/CT images localized radiotracer uptake to the left buccinator/buccal space, consistent with a buccinator lymph node, which is an inconsistent part of the facial lymphatic drainage. This case illustrates the added value of SPECT/CT and 3D reconstruction in sentinel lymph node localization, particularly in the head and neck.

Deep Vein Thrombosis Presenting on Pulmonary Ventilation and Perfusion Scintigraphy.

A 52-year-old woman presenting with dyspnea was referred for a ventilation and perfusion scan (VQ). VQ images (with Tc-DTPA [diethylene triamine pentaacetic acid aerosol] and Tc-MAA [macroaggregated albumin]) initially appeared normal; however, count rates on perfusion images were similar to ventilation images, implying little Tc-MAA had reached the lungs. Spot images of the injected extremity demonstrated focal Tc-MAA accumulation worrisome for a venous thrombus, subsequently confirmed by Doppler ultrasound. Careful attention to relative radiotracer count rates on VQ scans is crucial to ensure diagnostic utility. In addition, abnormal low perfusion radiotracer counts may unveil other pathology with important clinical implications.

Vesicocolic fistula detected by (99m)Tc-MAG3 renogram.

A 55-year-old man presented with 60-lb weight loss in 6 months. An abdominal CT demonstrated a large mass in the pelvis arising from the sigmoid colon and invading the urinary bladder. His elevated serum creatinine (1.25 mg/dL) triggered a request for a Tc-MAG3. Tc-MAG3 renogram demonstrated communication of the urinary bladder with the descending colon but no evidence of obstruction to drainage from the kidneys to the bladder. A retrograde cystogram confirmed a vesicocolic fistula. After multiple rounds of chemotherapy, the patient died 7 months later.