Value of 18-F-FDG PET/CT in assessment of patients with fever of unknown origin

Aim

To evaluate the value of 18F-FDG (positron emission tomography) PET/CT in assessment patients with fever of unknown origin (FUO) and to compare the findings with the results of the other investigations.

Spectrum of 18F-FDG PET/CT findings in patients presenting with fever of unknown origin

OBJECTIVE: The objective of this article is to provide an illustrative tutorial highlighting the clinical utility of (18)F-FDG PET/CT for imaging patients presenting with fever of unknown origin (FUO). CONCLUSION: FDG PET/CT is a powerful tool in localizing an inciting source in patients with FUO. The high sensitivity of FDG PET/CT for diagnosing infective, inflammatory, and neoplastic processes can be exploited in this setting because these processes are often the common causes of FUO.     

18F-FDG PET and PET/CT in fever of unknown origin.

Fever of unknown origin (FUO) was originally defined as recurrent fever of 38.3 degrees C or higher, lasting 2-3 wk or longer, and undiagnosed after 1 wk of hospital evaluation. The last criterion has undergone modification and is now generally interpreted as no diagnosis after appropriate inpatient or outpatient evaluation. The 3 major categories that account for most FUOs are infections, malignancies, and noninfectious inflammatory diseases. The diagnostic approach in FUO includes repeated physical investigations and thorough history-taking combined with standardized laboratory tests and simple imaging procedures. Nevertheless, there is a need for more complex or invasive techniques if this strategy fails. This review describes the impact of (18)F-FDG PET in the diagnostic work-up of FUO. (18)F-FDG accumulates in malignant tissues but also at the sites of infection and inflammation and in autoimmune and granulomatous diseases by the overexpression of distinct facultative glucose transporter (GLUT) isotypes (mainly GLUT-1 and GLUT-3) and by an overproduction of glycolytic enzymes in cancer cells and inflammatory cells. The limited data of prospective studies indicate that (18)F-FDG PET has the potential to play a central role as a second-line procedure in the management of patients with FUO. In these studies, the PET scan contributed to the final diagnosis in 25%-69% of the patients. In the category of infectious diseases, a diagnosis of focal abdominal, thoracic, or soft-tissue infection, as well as chronic osteomyelitis, can be made with a high degree of certainty. Negative findings on (18)F-FDG PET essentially rule out orthopedic prosthetic infections. In patients with noninfectious inflammatory diseases, (18)F-FDG PET is of importance in the diagnosis of large-vessel vasculitis and seems to be useful in the visualization of other diseases, such as inflammatory bowel disease, sarcoidosis, and painless subacute thyroiditis. In patients with tumor fever, diseases commonly detected by (18)F-FDG PET include Hodgkin's disease and aggressive non-Hodgkin's lymphoma but also colorectal cancer and sarcoma. (18)F-FDG PET has the potential to replace other imaging techniques in the evaluation of patients with FUO. Compared with labeled white blood cells, (18)F-FDG PET allows diagnosis of a wider spectrum of diseases. Compared with (67)Ga-citrate scanning, (18)F-FDG PET seems to be more sensitive. It is expected that PET/CT technology will further improve the diagnostic impact of (18)F-FDG PET in the context of FUO, as already shown in the oncologic context, mainly by improving the specificity of the method.     

Anatomo-metabolic characteristics of atelectasis in F-18 FDG-PET/CT imaging

PURPOSE: To evaluate the structural and metabolic characteristics of atelectasis in FDG-PET/CT. METHODS: Twenty one consecutive patients (13 males, 8 females, median age 67 years) with CT features of atelectasis, undergoing PET/CT imaging for preoperative staging of histologically proven malignancies (20 lung cancer and 1 ovarian cancer metastasis to lung), were included in the study. RESULTS: Hounsfield units of atelectasis (-383.58+/-189, range -631 to 82) were significantly higher than in normal lung (-756+/-67.46, range -839 to -555; P=0.0001), and lower than in malignant tissue (35+/-19, range 4-77; P=0.0001). The main patterns of FDG uptake observed in atelectasis were diffuse and homogenous. The standard uptake value (SUV) in atelectasis was low to moderate (SUV(avg): 1.13+/-0.50; SUV(max): 1.44+/-0.54), and generally lower than in tumor tissue (SUV(avg): 6.25+/-3.58, range 2.0-16.5), but always higher than in normal lung (0.56+/-0.18 and 0.70+/-0.23, respectively) (P=0.0001). There was a positive correlation between the density of atelectatic lesions and the degree of uptake, with no relationship to size. CONCLUSION: There is a positive relationship between the density of collapsed lung and the intensity of FDG uptake. FDG uptake in atelectasis is higher than in normal lung, and generally lower than in tumor tissue.     

Isolated cholangiolitis revealed by 18F-FDG-PET/CT in a patient with fever of unknown origin

Cholangiolitis, inflammation of the cholangioles, is difficult to diagnose by conventional imaging modalities. We report a case of cholangiolitis revealed by fluorine-18 fluoro desoxyglucose positron emission tomography-computerized tomography ((18)F-FDG-PET/CT) after about 9 months of recurrent fevers. A 20 years old girl with a history of recurrent fevers and repeated workups at different hospitals, which didn't diagnosed the source of fever, was admitted with a recent episode of fever. An (18)F-FDG-PET/CT was requested, which demonstrated focal hypermetabolic activity in the lateral segment of the left lobe of the liver. A liver biopsy showed inflammation of small biliary ducts consistent of cholangiolitis. Enterococcus casseliflavus was found on performed cultures. This represents the first case of cholangiolitis revealed by (18)F-FDG-PET/CT imaging.     

Diagnostic value of FDG-PET/(CT) in children with fever of unknown origin and unexplained fever during immune suppression

Purpose

Fever of unknown origin (FUO) and unexplained fever during immune suppression in children are challenging medical problems. The aim of this study is to investigate the diagnostic value of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) and FDG-PET combined with computed tomography (FDG-PET/CT) in children with FUO and in children with unexplained fever during immune suppression.

Methods

All FDG-PET/(CT) scans performed in the Radboud university medical center for the evaluation of FUO or unexplained fever during immune suppression in the last 10 years were reviewed. Results were compared with the final clinical diagnosis.

Results

FDG-PET/(CT) scans were performed in 31 children with FUO. A final diagnosis was established in 16 cases (52 %). Of the total number of scans, 32 % were clinically helpful. The sensitivity and specificity of FDG-PET/CT in these patients was 80 % and 78 %, respectively. FDG-PET/(CT) scans were performed in 12 children with unexplained fever during immune suppression. A final diagnosis was established in nine patients (75 %). Of the total number of these scans, 58 % were clinically helpful. The sensitivity and specificity of FDG-PET/CT in children with unexplained fever during immune suppression was 78 % and 67 %, respectively.

Conclusions

FDG-PET/CT appears a valuable imaging technique in the evaluation of children with FUO and in the diagnostic process of children with unexplained fever during immune suppression. Prospective studies of FDG-PET/CT as part of a structured diagnostic protocol are warranted to assess the additional diagnostic value.     

Dual-time-point F-18 FDG PET/CT for evaluation in patients with malignant lymphoma

Objective

The aim of this study was to evaluate the usefulness of F-18 fluorodeoxyglucose (FDG) dual-time-point (DTP) positron emission tomography (PET)/computed tomography (CT) with semiquantitative analyses for the initial staging in patients with malignant lymphoma.

Methods

Forty-three patients had DTP PET/CT, with 60-min and 2-h scan [n?=?8, Hodgkin??s lymphoma (HL); n?=?12, indolent non-Hodgkin lymphoma (NHL); n?=?23, aggressive NHL].

Results

A total of 524 lesions were evaluated (406 lymph nodes and 118 extra-nodal lesions). The maximum standardized uptake value (SUV_max) on 2-h delayed scan (SUV₂) was significantly higher than those on 1-h early scan (SUV₁) for all groups (P?<?0.0001 for HL; P?<?0.0001 for indolent NHL; P?<?0.0001 for aggressive NHL). Significant differences were detected between HL and indolent NHL, between indolent NHL and the aggressive NHL for both SUV₁ and SUV₂ (each P?<?0.0001). No significant differences were detected between HL and aggressive NHL for both SUV₁ and SUV₂ (P?=?0.6891 for SUV₁; P?=?0.8828 for SUV₂); however, significant differences were detected for the retention index of SUV_max between these groups (P?=?0.0238).

Conclusions

DTP F-18 FDG PET/CT with a semiquantitative technique may have the potential to provide the more accurate diagnoses for the staging of malignant lymphoma and the more important role in predicting the histological grades of malignancy compared with single-time-point F-18 FDG-PET scan.     

~(18)F-FDG PET/CT对不明原因发热病因的诊断价值

目的：探讨^18F-脱氧葡萄糖（FDG）PET/CT显像对不明原因发热（FUO）的影像学表现及病因诊断价值。方法：回顾性分析常规检查未能明确诊断FUO病因的45例患者^18F-FDG PET/CT显像资料,根据病理检查或临床随访结果分析^18F-FDG PET/CT显像结果,测量异常摄取病灶最大标准摄取值（SUVmax）。采用SPSS 11.0软件进行数据处理,SUVmax两样本均数比较采用t检验。结果：45例患者中35例^18F-FDG PET/CT全身显像发现至少有1处异常放射性浓聚灶,随访证实其中9例为恶性肿瘤,26例为感染或炎性病变,二者病变的SUVmax分别为6.09±1.46和2.57±1.33,差异有显著性意义（t=6.67,P〈0.05）;10例^18F-FDG PET/CT显像阴性患者,6例病因不明,4例为风湿性疾病。^18F-FDGPET/CT显像有助于临床FUO病因诊断。结论：全身^18F-FDG PET/CT显像在其它检查方法未能明确诊断FUO病因时,可为临床进一步诊断提供重要的参考价值。     

Diagnosis of Cardiac Metastasis from Endometrial Cancer by F-18 FDG-PET/CT

We report a case of a 59-year-old woman with right ventricular metastasis of undifferentiated endometrial cancer. Cardiac metastasis from endometrial cancer is a very rare finding. The case demonstrates that undifferentiated endometrial cancer is capable of metastasizing, presumably through a hematogenous route, to unexpected distant organs. These unexpected sites should not be undermined in the restaging and surveillance of these patients.     

18^F-FDG符合线路显像探测不明原因发热病灶的临床价值

目的探讨18^F-脱氧葡萄糖（FDG）双探头符合线路显像探测不明原因发热病灶的临床价值。方法对58例不明原因发热患者（体温超过38．3℃,发热持续时间至少3周）的18^F—FDG符合线路显像资料进行回顾性分析,将18^F—FDG符合线路显像结果与病理检查和随访结果进行比较;用感兴趣区（ROI）技术计算良恶性病变／正常组织放射性（L／B）比值,组间L／B比值比较采用t检验。结果48例（83％）患者有异常的18^F—FDG浓聚,其中20例为恶性病变,23例为感染或其他良性病变,5例未能确诊。58例中,10例（17％）符合线路显像阴性,其中4例为感染性疾病（2例尿路感染,2例淋巴结炎）,3例为结缔组织和胶原病（1例风湿病,1例成人still病,1例系统性红斑狼疮）,3例未能确诊。良恶性病灶的L／B比值分别为1．93±0．39和3．58±1．01,差异有统计学意义（t=6．955,P〈0．001）。结论符合线路显像可为探查不明原因发热患者的病灶提供有价值的临床信息。     

Peritoneal tuberculosis with elevated serum CA125 mimicking peritoneal carcinomatosis on F-18 FDG-PET/CT

18F-fluorodeoxyglucose positron emission tomography (F-18 FDG-PET) plays an important role in differentiating benign from malignant tumors. However, some false-positive findings, such as tuberculosis, may occur. We report a case referred for F-18 FDG whole-body PET computed tomography (PET/CT) scan owing to an elevated serum cancer antigen 125 (CA125). An FDG-PET/CT scan showed multiple hypermetabolic foci in the mesentery and peritoneum with further increase of FDG uptake on the delayed scan, mimicking peritoneal carcinomatosis. Subsequent laparoscopic biopsy showed granulomatous inflammation, and tuberculosis polymerase chain reaction showed a positive result. Serum CA125 returned to normal following treatment with anti-tuberculosis drugs. Peritoneal tuberculosis should be considered as a differential diagnosis in a tuberculosis endemic region.     

FDG PET/CT in evaluation of pyrexia of unknown origin

Pyrexia of unknown origin (PUO) is defined as fever above 38.5°C lasting for 3 weeks, of which at least 1 week has been spent in thorough investigation without a conclusive cause. Tuberculosis remains an important cause of PUO, particularly with the rising incidence of human immunodeficiency virus infection. It may strike virtually any organ in the body and can even mimic metastases especially in a known treated case of carcinoma. Bacterial infections, human immunodeficiency virus, hidden malignancy, sarcoidosis, and autoimmune disorders are some other important causes of PUO. Initial investigations include examination of blood, urine, stool, blood biochemistry, culture, etc. Typical radiologic investigations include chest radiography, computed tomography, and magnetic resonance imaging. Presented here is an atlas of cases where these investigations had been inconclusive but fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography demonstrated the site of pathology and directed histologic diagnosis.     

Role of integrated PET/CT with [18F]-FDG in the management of patients with fever of unknown origin: a single-centre experience

Purpose

Fever of unknown origin (FUO) is a diagnostic challenge for the wide range of possible causes involved. The aim of our work was to evaluate the role of [¹⁸F]-fluorodeoxyglucose positron emission tomography computed tomography ([¹⁸F]-FDG-PET/CT) in managing patients with classical FUO.

Materials and methods

Twenty-four consecutive patients (16 women, eight men; mean age, 56.5 years) with a diagnosis of FUO based on routine investigations were retrospectively studied. All underwent [¹⁸F]-FDG-PET/CT, which was considered true positive when the result was in agreement with the final diagnosis.

Results

A final diagnosis was reached in 17 of 24 patients (vasculitis, n=5; autoimmune disorder, n=2; neoplasm, n=3; infectious disease, n=6; biliary microlithiasis, n=1). In the remaining seven cases, no final diagnosis was established. PET-CT was useful in identifying aetiology in 11 patients, showing a diagnostic yield of 46% (11/24). Among the 11 cases with a negative PET scan, 10 did not show a worsening of the clinical condition.

Conclusions

This study underlines the crucial role of [¹⁸F]-FDG-PET/CT in managing patients with FUO. If prospective trials on this topic confirm the present findings, PET/CT should be incorporated in the routine diagnostic work-up of patients with classical FUO.     

68Ga-DOTATATE PET/CT in the evaluation of patients with neuroendocrine metastatic carcinoma of unknown origin

Objective

There is little evidence regarding the role of ⁶⁸Ga-DOTATATE PET/CT for the identification of primary tumors in patients with metastatic neuroendocrine carcinoma of unknown primary. The aim of this study is to assess the value of this technique in the mentioned clinical scenario.

Methods

We retrospectively studied twenty-nine patients (mean age 59.5 ± 10.6 years; female 17) with pathologically proven neuroendocrine metastases. In all cases conventional imaging was negative for primary tumor identification. ⁶⁸Ga-DOTATATE PET/CT was performed with a mean dose of 104.2 ± 18.8 MBq, using a 64-slice PET/CT with time-of-flight correction. A team of an experienced radiologist and a nuclear medicine physician evaluated the images. The maximum SUV (SUVm) was measured in all abnormal foci. Histopathology (when available) and/or clinical follow-up with correlative imaging was considered as reference standard.

Results

⁶⁸Ga-DOTATATE PET/CT identified the primary tumor in 17/29 (59 %) patients in the following locations: pancreas (n = 7), ileum (n = 7), duodenum (n = 1), colon (n = 1) and stomach (n = 1). In this population a significant correlation was found between SUVm of primary tumor and metastases (r = 0.815, P < 0.0001). Furthermore, additional sites of unsuspected metastases were demonstrated in 9 patients of this group and in 6 patients in whom no primary tumor was localized, mainly in lymph nodes and mesentery. Pathology confirmation was obtained in 7 patients who underwent surgery, whereas in the remaining 10 patients, correlative imaging and follow-up confirmed primary tumor localization.

Conclusions

⁶⁸Ga-DOTATATE PET/CT is a clinically useful imaging technique for the localization of primary tumors in patients with neuroendocrine metastatic carcinoma of unknown origin with the potential of having a significant impact in patient management and therapy planning.