Chi-Lai Ho

Dual-Tracer PET/CT Imaging in Evaluation of Metastatic Hepatocellular Carcinoma

We have reported previously that 11C-acetate (11C-ACT) PET was complementary to 18F-FDG PET in the evaluation of primary hepatocellular carcinoma (HCC) in relation to the degree of tumor cellular differentiation. In this retrospective study, our goals were to further explore the complementary role of 11C-ACT and 18F-FDG PET in the detection of metastatic HCC disease, to evaluate the tracer characteristics of individual organ metastasis, to identify the risk factors of metastasis, and to evaluate how these results could affect patient management. Methods: One hundred twenty-one patients were selected for this study. All patients had undergone a “dual-tracer” PET/CT same-day protocol with 11C-ACT PET/CT followed by 18F-FDG PET/CT. Sets of criteria were chosen to define “metastasis” and “no metastasis” on a patient basis. The patients considered as true-positive (n = 97) were then divided into 4 groups on the basis of their primary HCC tracer avidity: 18F-FDG-avid group, 11C-ACT-avid group, 18F-FDG- and 11C-ACT-avid group, and a posttreatment group with metastasis but no baseline dual-tracer PET characterization of the primary tumor and no hepatic recurrence. Results: On a patient basis, dual-tracer PET/CT had a sensitivity of 98%, a specificity of 86%, a positive predictive value of 97%, a negative predictive value of 90%, and an accuracy of 96% in the detection of HCC metastasis. On a lesion basis, 273 metastatic HCC lesions considered as true-positive were detected and categorized according to the organ or site of metastasis: lymph node (abdominal and thoracic, 49%), lung (32%), bone (8%), and others (10%). The lesion-based and patient-based detection sensitivities were 60% and 64%, respectively, by 11C-ACT and 77% and 79%, respectively, by 18F-FDG, and they were complementary. In analyzing lesion tracer avidity, there was a positive statistical correlation between primary HCC avidity with the general tendency of metastasis. Clinically significant changes in management were found in patients with true-positive metastasis, of whom 19% were affected by 11C-ACT PET alone. Dual-tracer PET/CT was more effective than single-tracer PET/CT in identifying candidates for curative therapy (negative predictive value of dual-tracer, 18F-FDG, and 11C-ACT PET/CT: 90%, 49%, and 37%, respectively). Conclusion: This study confirmed that 18F-FDG PET/CT is useful in the evaluation of HCC metastasis, although its role in the diagnosis of primary HCC is more limited. Dual-tracer PET/CT had an incremental value and complementary advantage when compared with single-tracer imaging in the evaluation of HCC metastasis.

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.

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.

68Ga-DOTATOC and 68Ga-PSMA PET/CT Unmasked a Case of Prostate Cancer With Neuroendocrine Differentiation

A bedridden 90-year-old man with fever and elevated prostate-specific antigen (PSA) (49 ng/mL) was referred for differentiation between infection and tumor. F-FDG PET/CT was negative for infection, but Ga-PSMA PET/CT showed multiple lesions in prostate gland with infiltration to bladder wall and seminal vesicle, consistent with locally advanced prostate cancer. The lesion with the highest Ga-PSMA uptake was strongly avid for Ga-DOTATOC, suggesting neuroendocrine tumor differentiation. After hormonal therapy, PSA normalized, but chromogranin-A increased (from 251 to 398 ng/mL), inferring progression of neuroendocrine tumor differentiation. Advanced prostate cancer may require investigation for pathological neuroendocrine transformation, although PSA may suggest improvement.

Imaging of Tumor Metabolism: PET with Other Metabolites

As the research of metabolic imaging is expanding, the clinical applications of radiolabeled substrates have also been increasing. Apart from glycolysis, other biochemical processes including amino acid synthesis, peptide and nucleic acid sequencing, lipid metabolism, signal transduction, and neurotransmitter-receptor interactions are also known to represent various forms of metabolic changes possibly found in tumor cells. In the literature, there are increasing amount of research studies on non-18F-FDG PET radiopharmaceuticals targeted for specific biochemical processes other than glycolysis. This chapter discusses on the basic biochemistry of non-18F-FDG PET tracers and how a good understanding of the underlying metabolic pathways of individual tracers leads to various clinical applications, particularly in the improvement of tumor detection, diagnosis, and patient management. Specific discussion is focused on 11C-acetate, 18F-acetate, 11C-choline, 18F-choline, 11C-methionine, 18F-DOPA, 18F-FLT, and Gallium-68 (68Ga)-labeled somatostatin analogs, primarily because these PET tracers have been investigated in greater biochemical and pharmaceutical details. Some have already been clinically confirmed useful, while others have great potentials to add to our understanding and to guide our research development on tumor metabolism and growth.