Sirong Chen

11C-Acetate and 18F-FDG PET/CT for Clinical Staging and Selection of Patients with Hepatocellular Carcinoma for Liver Transplantation on the Basis of Milan Criteria: Surgeon’s Perspective

The success of liver transplantation (LT) for hepatocellular carcinoma (HCC) is enhanced by careful patient selection on the basis of the Milan criteria. The criteria are traditionally assessed by contrast CT, which is known to be affected by structural or architectural changes in cirrhotic livers. We aimed to compare dual-tracer (11C-acetate and 18F-FDG) PET/CT with contrast CT for patient selection on the basis of the Milan criteria. Methods: Patients who had HCC and had undergone both preoperative dual-tracer PET/CT and contrast CT within a 1-mo interval were retrospectively studied. They then underwent either LT (n = 22) or partial hepatectomy (PH) (n = 21; HCC of ≤ 8 cm). Imaging data were compared with data from postoperative pathologic analysis for accuracy in assessment of parameters specified by the Milan criteria (tumor size and extent, vascular invasion, and metastasis), TNM staging, and patient selection for LT. Results: Dual-tracer PET/CT performed equally well in both LT and PH groups for HCC detection (94.1% vs. 95.8%) and TNM staging (90.9% vs. 90.5%). Contrast CT performed reasonably well in the LT group but not in the PH group for HCC detection (67.6% vs. 37.5%) and TNM staging (54.5% vs. 28.6%). In the LT group, the sensitivity and specificity of contrast CT for patient selection on the basis of the Milan criteria were 43.8% and 66.7%, respectively (comparable to values in the literature); the sensitivity and specificity of dual-tracer PET/CT were 93.8% and 100%, respectively (both Ps < 0.05). From the surgeon’s perspective, we tended to perform transplantation for patients with higher diagnostic certainty (stricter CT criteria) because of a shortage of donor grafts. Patients who were not transplant candidates usually underwent up-front hepatectomy without the benefit of reassessment contrast CT, resulting in lower accuracies for the PH group. The overall sensitivity (96.8%) and specificity (91.7%) of dual-tracer PET/CT for patient selection for LT were significantly higher than those of contrast CT (41.9% and 33.0%, respectively) (both Ps < 0.05). Sources of error for contrast CT were related to cirrhosis or previous treatment and included difficulty in differentiating cirrhotic nodules from HCC (39%) and estimation of tumor size (14%). Overstaging of vascular invasion (4.6%) and extrahepatic metastases (4.6%) was infrequent. The rate of false-negative results of dual-tracer PET/CT was 4.7%. Conclusion: Dual-tracer PET/CT was significantly less affected by cirrhotic changes than contrast CT for HCC staging and patient selection for LT on the basis of the Milan criteria. The inclusion of dual-tracer PET/CT in pretransplant workup may warrant serious consideration.

Molecular characterization of clinical isolates of Mycobacterium tuberculosis and their association with phenotypic virulence in human macrophages.

ABSTRACT Among 125 clinical isolates of Mycobacterium tuberculosis collected in Hong Kong and Shanghai, China, between 2002 and 2004, IS6110 typing revealed that 71 strains (57%) belonged to the Beijing family. The intracellular growth of the strains in human peripheral blood monocyte-derived macrophages was measured ex vivo on days 0, 3, 6, and 10. Among all tested strains, three hypervirulent strains showed significant increases in intracellular growth after 10 days of incubation. With an initial bacterial load of 104 CFU, most of the clinical isolates and H37Ra (an avirulent strain) exhibited no intracellular survival on day 10, while the three hypervirulent strains together with H37Rv (a virulent strain) showed on average a two- to fourfold rise in CFU count. These three hypervirulent strains belonging to a non-Beijing family were isolated from patients suffering from tuberculosis meningitis. Cytokines secreted by gamma interferon-activated macrophages were measured daily after challenge with selected strains of M. tuberculosis. The levels of tumor necrosis factor alpha were elevated after 24 h of infection among all strains, but the levels were significantly lower among the three hypervirulent strains, whereas interleukin 10 (IL-10) and IL-12 were not detected. Results were concordant with the differential expression of the corresponding cytokine genes in activated macrophages, as monitored by real-time PCR. Our findings highlighted that these three hypervirulent strains may possess an innate mechanism for escaping host immunity, which accounts for their characteristic virulence in patients presenting with a more severe form of disease.

Dual-tracer PET/CT in renal angiomyolipoma and subtypes of renal cell carcinoma.

&NA; We studied the metabolic characteristics of RCC subtypes and angiomyolipoma with 18F-FDG and 11C-acetate PET/CT. Methods Fifty-eight patients with both baseline CT and dual-tracer PET/CT were recruited: 10 angiomyolipoma (16 lesions) and 48 RCC (50 lesions). Each lesion was assessed for SUVmax ratio (lesion-to-normal kidney) on 11C-acetate/18F-FDG PET and attenuation density on CT. Receiver operating characteristic (ROC) curve was analyzed to define the threshold of 11C-acetate SUVmax ratio for differentiating angiomyolipoma from RCC. Thirty-nine RCC patients were selected for 3-year disease-free survival analysis. Results All angiomyolipoma showed negative 18F-FDG but markedly increased 11C-acetate metabolism, significantly higher than RCC (11C-acetate SUVmax ratio = 4.11 ± 0.53 vs 2.00 ± 0.71; P < 0.05). 11C-acetate SUVmax ratio = 3.71 could differentiate angiomyolipoma including “fat-poor angiomyolipoma” (n = 10) from RCC with sensitivity of 93.8% (15/16) and specificity of 98.0% (49/50). Different RCC subtypes/grades (25 low- and 11 high-grade clear cell [CC], 7 chromophobe, 4 papillary, and 1 collecting duct) were found to have different dual-tracer metabolic pattern (P < 0.05), with overall RCC detection sensitivity of 90% (45/50). All chromophobe RCC were avid only for 11C-acetate but not 18F-FDG, whereas papillary RCC were primarily the opposite. RCC-CC showed variable dual-tracer uptake: high-grade more avid for 18F-FDG, low-grade more for 11C-acetate. Four RCC cases negative by dual-tracers were of low-grade RCC-CC. “Primary RCC being 18F-FDG-avid” was the only independent predictor of RCC recurrence in 3 years (P < 0.05), with a median disease-free survival of 22 months. Conclusion 11C-acetate PET/CT helps in differentiating “fat-poor angiomyolipoma” from RCC. Dual-tracer PET/CT has value in diagnosis of RCC subtypes and predicting survival.

PET/CT Characteristics of Isolated Bone Metastases in Hepatocellular Carcinoma

PURPOSE To compare the prognostic implications and positron emission tomography (PET)/computed tomography (CT) characteristics of isolated bone metastasis secondary to hepatocellular carcinoma (HCC) with those of HCC metastases to bone and other sites. MATERIALS AND METHODS This study was approved by the institutional ethics committee, and informed consent was obtained from all patients. Extrahepatic metastases were diagnosed in 257 patients with HCC by using dual-tracer (carbon 11 [(11)C] acetate and fluorine 18 fluorodeoxyglucose [FDG]) PET/CT. Metastatic bone lesions were identified with visual inspection and semiquantitative assessment and confirmed with histopathologic examination and/or supported by findings at other radiologic examinations or serial PET/CT. RESULTS The frequency of bone metastasis from HCC was 19% (49 of 257 patients; eight patients had histopathologic proof and 41 had imaging proof). Metastasis isolated to bone (group 1, 30 of 257 patients [12%]) was more common than metastasis to bone and other sites (group 2, 19 of 257 patients [7%]). At lesion-based analysis of group 1 (71 index lesions; mean lesion size ± standard deviation, 3.25 cm ± 1.88), (11)C acetate PET was more sensitive than FDG PET (93% [66 of 71 lesions] vs 62% [44 of 71 lesions], respectively; P < .05). The combined sensitivity was 97% (69 of 71 lesions) with dual-tracer PET and 72% (51 of 71 lesions) with CT. At patient-based analysis, (11)C acetate PET had an incremental value of 23% (seven of 30 patients) over FDG PET. At lesion-based analysis of group 2, FDG PET was more sensitive than (11)C acetate PET (87% [33 of 38 lesions] vs 50% [19 of 38 lesions], respectively; P < .05). Tracer avidities of metastatic bone lesions were closely correlated with that of their corresponding primary HCC tumors. The median survival time was longer in group 1 than in group 2 (18 months vs 11 months, respectively; P < .05). CONCLUSION Isolated bone metastasis from HCC may not be as uncommon as previously believed. The detection of these metastases can be significantly enhanced with (11)C acetate PET compared with FDG PET alone. Identification of this group of patients also seems to have prognostic importance.

Differential fadE28 expression associated with phenotypic virulence of Mycobacterium tuberculosis

Ability to persist in human macrophages is central to the virulence of Mycobacterium tuberculosis and is not invariable among various strains. Differential gene expression that is associated with phenotypic virulence may provide additional information of virulent genes involved in the pathogenesis of M. tuberculosis, which is not fully elucidated. Three hypervirulent strains of M. tuberculosis isolated from patients suffering with tuberculous meningitis were shown to grow more rapidly inside human macrophages in a previous study. In the current investigation, expression of 7 mycobacterial genes (fadE28, mce1A, mymA, acr, sigA, sugC, and Rv3723) of these strains during ex vivo macrophage challenge and in vitro acid shock was quantified by real-time PCR. Using rrs gene as a normalisation gene, fadE28 gene exhibited differential gene expression that is associated with phenotypic virulence, whereas the other 6 genes showed indistinguishable expression patterns. Up-regulation of fadE28 gene in the hypervirulent strains may account for virulence by increasing the efficiency of beta-oxidation, which is important for the persistence in macrophages as M. tuberculosis uses fatty acids preferably inside phagosome of macrophages. The fadE28 gene, together with its adjacent genes may also be critical in the process of lipid modification that could facilitate parasitism in human macrophages.

11C-Acetate PET/CT for Metabolic Characterization of Multiple Myeloma: A Comparative Study with 18F-FDG PET/CT

We prospectively compared 11C-acetate with 18F-FDG in a PET/CT evaluation of multiple myeloma (MM), specifically on diagnostic accuracy, identification of high-risk patients, and monitoring of treatment response. Methods: Dual-tracer PET/CT was performed on 35 pathologically and clinically confirmed and untreated patients (26 with symptomatic MM, 5 with smoldering MM, and 4 with monoclonal gammopathy of unknown significance) and 20 individuals with normal marrow. Results: 11C-acetate showed significant incremental value over 18F-FDG (84.6% vs. 57.7%) for positively identifying patients with diffuse and focal symptomatic MM, and was negative in patients with indolent smoldering MM and monoclonal gammopathy of unknown significance. Three functional parameters—number of 11C-acetate–avid and 18F-FDG–avid focal bone lesions and 11C-acetate general marrow activity—strongly correlated with β-2-microglobulin as surrogate imaging markers of tumor burden. After induction chemotherapy, the metabolic change in 11C-acetate general marrow activity correlated with clinical response. Conclusion: Metabolic characterization of MM in diagnosis, risk stratification, and treatment monitoring can be done more accurately by assessing lipid metabolism with 11C-acetate than by assessing glucose metabolism with 18F-FDG.

[18F]Fluoroacetate Positron Emission Tomography for Hepatocellular Carcinoma and Metastases: An Alternative Tracer for [11C]Acetate?

[11C]Acetate (ACT) positron emission tomography/computed tomography (PET/CT) is useful in the detection of hepatocellular carcinoma (HCC). This study aimed to evaluate whether [18F]fluoroacetate (FAC) could be an alternative analogue of [11C]ACT for the diagnosis of HCC. [18F]FAC was synthesized using the precursor t-butyl 2-(methanesulfonyloxy)ethanoate. Five volunteer patients with known HCC were recruited after consent. Whole-body [18F]FAC PET/CT was performed at 20 minutes and 1 hour postinjection and compared to [11C]ACT PET/CT at 20 minutes postinjection to assess biodistribution and tumor uptake characteristics. Qualitative and semiquantitative analyses were performed with statistical correlations on the physiologic organs of accumulation and HCC lesions for both tracers. [18F]FAC was obtained with 99% radiochemical purity, and the reaction yield was 16.0% with 1-hour synthesis time. The biodistribution of [18F]FAC on PET/CT was significantly different from that of [11C]ACT (p < .05) by the lack of preferential uptake in any specific organ, particularly the pancreas, resembling the pattern of blood-pool retention although partly metabolized via the bowel. There was no significant defluorination, and none of the [11C]ACT-avid HCC lesions showed increased [18F]FAC activity. These were different from the results reported on other species. [18F]FAC may not be a potential alternative tracer for [11C]ACT in PET/CT evaluation of HCC in human subjects.

11C-acetate PET/CT in multicentric angiomyolipoma of the kidney.

A 35-year-old woman with a left kidney mass was diagnosed on ultrasound and CT; however, the diagnosis was inconclusive and therefore she underwent dual-tracer (C-acetate and F-18 FDG) PET/CT. C-acetate PET/CT identified an exophytic lesion in the left kidney and a chain of left para-aortic nodes from left renal vein level to aortic bifurcation with markedly increased metabolism (C-acetate lesion-to-kidney SUV ratio (SUVL/K) 4.8 and 4.9, respectively) but no abnormal F-18 FDG uptake. The diagnosis of “multicentric angiomyolipoma with low-fat content or angiomyolipoma with malignant transformation and metastases” was suggested. The pathologic diagnosis post partial nephrectomy and lymph nodes resection was “angiomyolipoma with lymph node involvement.”

F-18 FDG PET/CT in an adult case of group B streptococcal sacroiliitis.

An adult patient presented with acute severe pelvic and low-back pain. Evaluations with CT and MRI were negative/inconclusive. F-18 FDG PET/CT localized the site of pathology in right sacroiliac-joint by demonstrating hypermetabolic activities conformal with the joints outline, signifying infectious/inflammatory sacroiliitis. Blood culture was positive for Group B streptococcus (GBS). Antibiotic treatment was started within 24 hours from onset of symptoms, and there was almost immediate partial pain relief. GBS sacroiliitis is a rare form of septic sacroiliitis requiring prompt diagnosis and urgent treatment. This is the first report of F-18 FDG PET/CT for diagnosing GBS sacroiliitis in adults with no predisposing factors.

11C-Acetate PET/CT in a Case of Recurrent Hemangiopericytoma

Intracranial hemangiopericytoma (IHPC) is a rare tumor representing less than 1% of all CNS tumors and is often indistinguishable from meningioma on structural imaging alone. Unlike meningioma, IHPC is an aggressive tumor with the propensity for early locoregional recurrence and distant metastases. Hence, its management strategies differ greatly from that of meningioma. Some investigators have reported the potential role of multitracers (F-FDG, C-methionine, and O-H2O) PET imaging in distinguishing IHPC from meningioma. We described the findings of dual-tracer (C-acetate and F-FDG) PET/CT imaging in a histopathologically proven case of IHPC with extensive extracranial osseous metastases that showed significantly greater C-acetate avidity.