Positron emission tomography with 2-[18F]fluoro-2-deoxy-D-glucose in oncology

The tumoral uptake of 2-[18F]fluoro-2-deoxy-D-glucose (18FdGlc) is based upon enhanced glycolysis. Positron-emission tomography (PET) using 18FdGlc provides the physiological and metabolic information. 18FdGlc PET has been used successfully for assessing primary tumours and metastases, prognosis, and planning and for monitoring tumour therapy as well as for early detection of recurrent tumour growth. This review summarises the uptake mechanism of 18FdGlc in benign and malignant lesions, its relation to histopathology, and its clinical value for detecting and staging primary tumours.     

18F]fluoro-2-deoxy-D-glucose ([18F]FDG) positron emission tomography imaging of thymic carcinoid tumor presenting with recurrent Cushing's syndrome

We report a case of a young woman with Cushing's syndrome (CS), in whom although endocrine investigations and negative pituitary imaging were suggestive of ectopic ACTH secretion, the results of inferior petrosal sinus (IPS) sampling after coricotropin-releasing hormone (CRH) stimulation were suggestive of pituitary ACTH hypersecretion. (111)In-labelled octreotide and high-resolution computer tomography (CT) revealed a lesion possibly responsible for the ACTH source in the thymus. Thymectomy confirmed concomitant ectopic CRH and probable ACTH production by a thymic neuroendocrine carcinoma. After an 8-year remission period the patient developed a clinical and biochemical relapse. A high-resolution computed tomography (CT) scan of the thorax showed a 2-cm nodule in the thymic bed, which was positive on a [(18)F]fluoro-2-deoxy-D-glucose ([(18)F]FDG) positron emission tomography (PET) scan. However, a repeated thymectomy did not result in remission. A repeat [(18)F]FDG PET study showed persistent disease in the thymic bed and also uptake in the adrenals. The patient underwent bilateral adrenalectomy, which resulted in clinical remission. A further [(18)F]FDG PET scan 8 months later showed no progression of the thymic tumor and confirmed complete excision of the adrenals. This is a rare case of concomitant CRH and ACTH secretion from a thymic carcinoid tumor; the case illustrates the usefulness of functional imaging with [(18)F]FDG PET in the diagnosis, management and follow-up of neuroendocrine tumors.     

Positron emission tomography with [(18)F]fluoro-2-deoxy-D-glucose for diagnosis and staging of bile duct cancer

Malignant tumors with high glucose metabolic rates accumulate [18F]-fluorodeoxyglucose (FDG), a positron emitting tracer. The aim of this study was to evaluate FDG positron emission tomography (PET) for detection and staging of human cholangiocarcinoma (CC). Patients with adenocarcinoma of the biliary tree (n = 26), with benign lesions of the bile ducts (n = 8), and 20 control patients underwent FDG-PET (370 MBq [18F]-FDG, Siemens ECAT EXACT HR(+)). In a blinded fashion, 4 independent experts evaluated the PET scans visually and semiquantitatively using the standardized uptake value and a tumor/non-tumor ratio. All adenocarcinomas and benign lesions (sclerosing cholangitis, bile duct adenoma, Caroli's disease) were histologically proven and imaged by magnetic resonance imaging and endoscopic retrograde cholangioscopy. True-positive PET scans were obtained in 24 of 26 CC and false-negative scans in the other 2 (sensitivity 92.3%). The PET scan was true-negative in 18 of 20 controls and in all 8 benign biliary lesions (specificity 92.9%). Visual and semiquantitative evaluation using tumor/non-tumor ratios were equally accurate (accuracy 92.6%) whereas evaluation by standardized uptake value revealed lower accuracy (P <.05). Regional or hepatoduodenal lymph node metastases were detected with PET in only 2 of 15 cases whereas distant metastases (peritoneal carcinomatosis, pulmonary metastases) were diagnosed in 7 of 10 cases. In conclusion, PET is highly sensitive and specific for the detection and localization of CC. It can be helpful for diagnosis of distant metastases but is not suitable for detection of regional lymph node metastases.     

Positron emission tomography with 2-[18F]-fluoro-2-deoxy-D-glucose in oncology

Positron emission tomography (PET) using ¹⁸F-fluorodeoxyglucose (FDG) is considered to be a very useful adjunct to anatomic imaging techniques and is now primarily used for oncological indications. These indications include diagnosis, staging, and therapy monitoring. In this review, we discuss the articles in which FDG-PET is clinically used for monitoring therapy in breast cancer, lymphomas and gliomas. It is found that the amount of FDG uptake strongly correlates with response to therapy in breast cancer, lymphomas, and gliomas; a decrease in FDG uptake after therapy indicates a positive response to therapy. However, this conclusion is based on small patient numbers, whereas the exact response mechanism is still unknown. Therefore, more studies in comparable patient groups are required to achieve a better understanding of FDG uptake patterns after therapy. Part IIIb deals with lung, and head and neck cancer, hepatocellular and colorectal tumours, and sarcoma. Received: 2 May 2000 / Accepted: 28 July 2000     

Positron emission tomography with 2-[18F]-fluoro-2-deoxy-D-glucose in oncology

Positron emission tomography (PET) using 18F-fluorodeoxyglucose (FDG) is considered to be a very useful adjunct to anatomic imaging techniques and is now primarily used for oncological indications. These indications include diagnosis, staging, and therapy monitoring. In this review, we discuss the articles in which FDG-PET is clinically used for monitoring therapy in lung and colorectal tumours, head and neck cancer, sarcoma, and hepatocellular carcinoma. It is found that the amount of FDG uptake strongly correlates with response to therapy: a decrease in FDG uptake after therapy indicates a positive response to therapy. However, this conclusion is based on small numbers of patients, whereas the exact response mechanism is still unknown. Moreover, in these case series, the interval between tumour therapy and FDG-PET, as well as the method of quantification, SUV or tumour-to-non-tumour ratios, differ per study. Finally, dynamic imaging is a recommended technique by some authors, but it is not a standard technique in clinical practice to evaluate tumour therapy. Therefore, further study is required which has to deal with these major issues before it is possible to draw definite conclusions.     

Detection of primary and metastatic lesions by [18F]fluoro-2-deoxy-D-glucose PET in a patient with thymic carcinoid

We present a case of thymic carcinoid, in which primary and metastatic lesions of lymph nodes and bones could be detected by [(18)F]fluoro-2-deoxy-D-glucose (FDG)-PET, but not by (123)I-meta-iodobenzylguanidine ((123)I-MIBG) SPECT, or by (99m)Tc-methylene diphosphonate ((99m)Tc-MDP) bone scintigraphy. FDG-PET may be a useful tool for managing thymic carcinoids in patients with negative results on (123)I-MIBG SPECT or (99m)Tc-MDP imaging.     

18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in aggressive lymphoma: an early prognostic tool for predicting patient outcome

Assessment of early therapeutic response using metabolic imaging is potentially useful to determine prognosis in aggressive lymphoma. Between January 2000 and January 2004, 90 patients with newly diagnosed aggressive lymphoma (median age 53 years, 94% diffuse large B-cell) were prospectively explored with [18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) prior to induction chemotherapy, after 2 cycles ("early PET"), and after induction completion. Therapeutic response was evaluated using conventional diagnostic methods at 4 cycles. Induction treatment with an anthracycline-containing regimen was administered to all patients, associated with rituximab in 41%. According to the International Prognostic Index (IPI), 37 patients and 53 patients belonged to the lower- and higher-risk groups, respectively. At midinduction, "early PET" was considered negative in 54 patients and positive in 36. After completion of induction, 83% of PET-negative patients achieved complete remission compared with only 58% of PET-positive patients. Outcome differed significantly between PET-negative and PET-positive groups; the 2-year estimates of event-free survival reached 82% and 43%, respectively (P < .001), and the 2-year estimates of overall survival reached 90% and 61%, respectively (P = .006). Predictive value of "early PET" was observed in both the lower-risk and higher-risk groups, indicating prognostic independence from the IPI. Therefore, FDG-PET should be an early guide to first-line strategies in aggressive lymphoma.     

Incidental detection of thoracic sarcoidosis on whole-body 18fluorine-2- fluoro-2-deoxy-D-glucose positron emission tomography

18 Fluorine-2- Fluoro-2-Deoxy-D-Glucose positron emission tomography (18FDG PET) allows imaging of sites with increased metabolic activity. Increased metabolic activity in mediastinal nodes in sarcoidosis has been described. We report the prospective diagnosis of thoracic sarcoidosis on 18FDG PET based on extensive, peripheral, upper lobe parenchymal, and mediastinal nodal tracer uptake.     

Real-time prognosis for metastatic thyroid carcinoma based on 2-[18F]fluoro-2-deoxy-D-glucose-positron emission tomography scanning

CONTEXT/OBJECTIVE: Approximately 15% of thyroid cancer patients develop subsequent metastases. The clinical course of patients with metastatic thyroid carcinoma is highly variable. We hypothesized that the metabolic activity of metastatic lesions, as defined by retention of 2-[(18)F]fluoro-2-deoxyglucose (FDG), would correlate with prognosis. DESIGN/PATIENTS: The initial FDG-positron emission tomography (PET) scans from 400 thyroid cancer patients were retrospectively reviewed and compared with overall survival (median follow-up, 7.9 yr). We examined the prognostic value of clinical information such as gender, age, serum thyroglobulin, American Joint Committee on Cancer (AJCC) stage, histology, radioiodine avidity, FDG-PET positivity, number of FDG-avid lesions, and the glycolytic rate of the most active lesion. RESULTS: Age, initial stage, histology, thyroglobulin, radioiodine uptake, and PET outcomes all correlated with survival by univariate analysis. However, only age and PET results continued to be strong predictors of survival under multivariate analysis. The initial American Joint Committee on Cancer stage was not a significant predictor of survival by multivariate analysis. There were significant inverse relationships between survival and both the glycolytic rate of the most active lesion and the number of FDG-avid lesions. CONCLUSIONS: FDG-PET scanning is a simple, expensive, but powerful means to restage thyroid cancer patients who develop subsequent metastases, assigning them to groups that are either at low (FDG negative) or high (FDG positive) risk of cancer-associated mortality. We propose that the aggressiveness of therapy for metastases should match the FDG-PET status.     

Human adipose tissue glucose uptake determined using [18F]-fluoro-deoxy-glucose ([18F]FDG) and PET in combination with microdialysis

Aims/hypothesis: To determine the lumped constant (LC), which accounts for the differences in the transport and phosphorylation between [¹⁸F]-2-fluoro-2-deoxy-d-glucose ([¹⁸F]FDG) and glucose, for [¹⁸F]FDG in human adipose tissue. Methods: [¹⁸F]FDG-PET was combined with microdialysis. Seven non-obese (29 ± 2 years of age, BMI 24 ± 1 kg/m²) and seven obese (age 32 ± 2 years of age, BMI 31 ± 1 kg/m²) men were studied during euglycaemic hyperinsulinaemia (1 mU/kg · min^–1 for 130 min). Abdominal adipose tissue [¹⁸F]FDG uptake (rGU_FDG) and femoral muscle glucose uptake were measured using [¹⁸F]FDG-PET. Adipose tissue perfusion was measured using [¹⁵O]-labelled water and PET, and interstitial glucose concentration using microdialysis. Glucose uptake (by microdialysis, rGU_MD) was calculated by multiplying glucose extraction by regional blood flow. The LC was determined as the ratio of rGU_FDG to rGU_MD. Results: Rates of adipose tissue glucose uptake (rGU_MD) were 36 % higher in the non-obese than in the obese patients (11.8 ± 1.7 vs 7.6 ± 0.8 μmol/kg · min^–1, p < 0.05, respectively) and a correlation between rGU_MD and rGU_FDG was found (r = 0.82, p < 0.01). The LC averaged 1.14 ± 0.11, being similar in the obese and the non-obese subjects (1.01 ± 0.15 vs 1.26 ± 0.15, respectively, NS). Muscle glucose uptake was fourfold to fivefold higher than adipose tissue glucose uptake in both groups. Conclusion/interpretation: [¹⁸F]FDG-PET seems a feasible tool to investigate adipose tissue glucose metabolism in human beings. Direct measurements with [¹⁸F]FDG-PET and microdialysis suggest a LC value of 1.14 for [¹⁸F]FDG in human adipose tissue during insulin stimulation and the LC does not appear to be altered in insulin resistance. Furthermore, the obese patients show insulin resistance in both adipose tissue and skeletal muscle. [Diabetologia (2001) 44: 2171–2179] Received: 10 May 2001 and in revised form: 29 August 2001     

Diagnosis of pancreatic cancer by 2[18F]-fluoro-2-deoxy-D-glucose positron emission tomography.

The detection of pancreatic cancer or the discrimination between pancreatic cancer and chronic pancreatitis remains an important diagnostic problem. The increased glucose metabolism in malignant tumours formed the basis for this investigation, which focused on the role of positron emission tomography (PET) with 2[18F]-fluoro-2-deoxy-D-glucose (FDG) in the detection of pancreatic cancer and its differentiation from chronic pancreatitis. Eighty patients admitted for elective pancreatic surgery received preoperatively 250-350 mBq FDG intravenously and emission scans were recorded 45 minutes later. Intense focal activity in the pancreatic region was taken at the time of scanning as showing the presence of pancreatic cancer. The presence of cancer was later confirmed by histological examination of the surgical specimens and histological findings were compared with the preoperative PET results. Forty one patients with pancreatic cancer (group I: n = 42) had a focally increased FDG uptake in the pancreatic region. Two patients with a periampullary carcinoma (group II: n = 6) failed to develop FDG accumulation. In 28 patients with chronic pancreatitis (group III: n = 32) no FDG accumulation occurred. Overall sensitivity and specificity of PET for malignancy (group I + II) were 94% (45 of 48) and 88% (28 of 32), respectively. The standard uptake value of the patients with pancreatic carcinoma was significantly higher than in patients with chronic pancreatitis (3.09 (2.18) v 0.87 (0.56); p < 0.001; median (interquartile range)). These findings show that FDG-PET represents a new and non-invasive diagnostic procedure for the diagnosis of pancreatic cancer and to differentiate pancreatic cancer from chronic pancreatitis. However, the diagnostic potential of this technique requires further evaluation.     

A case of cryptococcal pneumonia with false-positive [18F]fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) image mimicking lung metastatic cancer

BackgroundThere is an increasing use of positron emission tomography with [¹⁸F]fluoro-2-deoxy-d-glucose (FDG-PET) for differential diagnosis between lung malignancy and other pulmonary diseases such as infection. However, false-positive FDG-PET images mimicking lung cancer can occur in pulmonary infection.ObjectiveThis study was to describe a case of cryptococcal pneumonia with false-positive FDG-PET image mimicking metastatic lung cancer.Patient and resultsWe analyzed the clinical features and chest CT and FDG-PET characteristics of a case of pulmonary cryptococcosis that was initially suspected to have lung metastasis of gastric cancer and treated by surgery. During a follow-up, the 49 years old, female patient with a 7-year history of gastric adenocarcinoma showed a 1.0-cm nodule in the right lower lobe of lung on her chest CT scan with an accumulation of FDG (SUV = 4.5) on her PET image. With a clinical diagnosis of suspected lung metastatic cancer, the lung wedge resection was then performed. Histological analysis of the resected nodule confirmed a diagnosis of cryptococcal pneumonia.ConclusionThe FDG-PET image is not particularly helpful in segregating pulmonary infection from lung malignancy in certain cases. Surgical resection is recommended for both diagnosis and treatment of pulmonary cryptococcosis.     

An autoradiographic study of [(18)F]FDG uptake to islets of Langerhans in NOD mouse

To evaluate the potential of in vivo imaging of accumulation of lymphocytes to islets of Langerhans (insulitis), we compared 2-[¹⁸F]fluoro-2-deoxy-d-glucose ([¹⁸F]FDG) uptake in the pancreas and pancreatic islets of healthy BALB/c mice, phenotypically healthy NOD mice with insulitis and diabetic NOD mice. [¹⁸F]FDG was injected i.v. to 14 female BALB/c mice (age 13 ± 3 weeks, plasma glucose 8 ± 2 mmol/l) and 21 age-matched female NOD mice (plasma glucose 8 ± 4 mmol/l, p = 0.06). The mice were killed 90-min post injection and distribution of radioactivity was analysed using digital autoradiography. There was no correlation of plasma glucose concentration with the [¹⁸F]FDG uptake values. Uptake of radioactivity in NOD mice to the islets affected by insulitis was up to 2.3 times higher (p = 0.001) than that to unaffected islets in the same pancreas. Uptake to NOD islets with insulitis was also clearly enhanced (1.0–2.3 times higher) compared to the islets in the BALB/c mice.

In conclusion, NOD mouse islets with insulitis accumulate [¹⁸F]FDG markedly more than islets without insulitis or BALB/c islets. However, the relatively small difference in the [¹⁸F]FDG intensity between healthy and diseased islets, combined with the limited resolution ability of the positron emission tomography (PET), probably prevent the use of [¹⁸F]FDG in PET studies aiming at in vivo documentation of onset and progression of insulitis and prediabetes in mouse and man.     

Positron emission tomography with fluoro-2-deoxy-D-glucose (FDG-PET) in the staging of post transplant lymphoproliferative disorder in lung transplant recipients

Posttransplantation lymphoproliferative disorder (PTLD) is a histologic heterogeneous disease that complicates 4 to 8% of lung transplant recipients. Disease extent is an important prognostic factor and may affect therapy. Positron emission tomography with fluoro-2-deoxy-D-glucose (FDG-PET) has proven useful for staging high-grade lymphomas but is less accurate for staging low-grade and extranodal lymphoma. This study examined our initial experience using FDG-PET imaging to stage lung transplant recipients with posttransplantation lymphoproliferative disorder. FDG can show foci of uptake, particularly in extrathoracic sites, not seen by conventional imaging, which allows more accurate staging of disease thereby yielding useful prognostic information and guiding therapy.     

Role of F-18 FDG positron emission tomography (PET) in the assessment of myocardial viability

Positron emission tomography (PET) is a functional imaging technique with important clinical applications in cardiology, oncology, and neurology. In cardiac imaging, its role has been extensively evaluated in the noninvasive diagnosis of coronary artery disease and in the determination of prognosis. Additionally, cardiac PET with F-18 fluorodeoxyglucose (FDG) is very helpful in selection of patients with coronary artery disease and left ventricular dysfunction who would benefit from coronary artery revascularization. Cardiac PET is arguably considered by many as a gold standard in this particular application. F-18, unlike other positron emitters, has a reasonably long physical half-life, which permits its distribution through commercial radiopharmacies. This is further facilitated by increasing popularity of FDG PET in oncology, which makes cardiac FDG PET a practical option for hospitals and outpatient centers equipped with PET scanners. In addition, gamma camera single photon emission computed tomography (SPECT) systems, routinely used in nuclear medicine departments, can be equipped with coincidence circuit or high-energy 511 KeV collimators, providing a cost-effective means of FDG cardiac imaging. Myocardial utilization of glucose as a substrate is variable, depending, among other factors, on serum levels of glucose and insulin. Therefore, patient preparation is important in obtaining good-quality images and in turn allowing for accurate interpretation of myocardial viability. There are various protocols to choose from that provide diagnostic image quality in both diabetic and nondiabetic patients. Mismatch between blood flow and FDG metabolism, an indicator of viable, jeopardized myocardium, can predict postrevascularization improvement in left ventricular function, symptomatic relief, and long-term survival.