Imaging cardiac amyloidosis: a pilot study using 18F-florbetapir positron emission tomography

Purpose

Cardiac amyloidosis, a restrictive heart disease with high mortality and morbidity, is underdiagnosed due to limited targeted diagnostic imaging. The primary aim of this study was to evaluate the utility of ¹⁸F-florbetapir for imaging cardiac amyloidosis.

Methods

We performed a pilot study of cardiac ¹⁸F-florbetapir PET in 14 subjects: 5 control subjects without amyloidosis and 9 subjects with documented cardiac amyloidosis. Standardized uptake values (SUV) of ¹⁸F-florbetapir in the left ventricular (LV) myocardium, blood pool, liver, and vertebral bone were determined. A ¹⁸F-florbetapir retention index (RI) was computed. Mean LV myocardial SUVs, target-to-background ratio (TBR, myocardial/blood pool SUV ratio) and myocardial-to-liver SUV ratio between 0 and 30 min were calculated.

Results

Left and right ventricular myocardial uptake of ¹⁸F-florbetapir were noted in all the amyloid subjects and in none of the control subjects. The RI, TBR, LV myocardial SUV and LV myocardial to liver SUV ratio were all significantly higher in the amyloidosis subjects than in the control subjects (RI median 0.043 min^?1, IQR 0.034 – 0.051 min^?1, vs. 0.023 min^?1, IQR 0.015 – 0.025 min^?1, P?=?0.002; TBR 1.84, 1.64 – 2.50, vs. 1.26, IQR 0.91 – 1.36, P?=?0.001; LV myocardial SUV 3.84, IQR 1.87 – 5.65, vs. 1.35, IQR 1.17 – 2.28, P?=?0.029; ratio of LV myocardial to liver SUV 0.67, IQR 0.44 – 1.64, vs. 0.18, IQR 0.15 – 0.35, P?=?0.004). The myocardial RI, TBR and myocardial to liver SUV ratio also distinguished the control subjects from subjects with transthyretin and those with light chain amyloid.

Conclusion

¹⁸F-Florbetapir PET may be a promising technique to image light chain and transthyretin cardiac amyloidosis. Its role in diagnosing amyloid in other organ systems and in assessing response to therapy needs to be further studied.     

18-Fluorodeoxyglucose imaging with positron emission tomography and single photon emission computed tomography: cardiac applications

The assessment of myocardial viability has become an important aspect of the diagnostic and prognostic work-up of patients with ischemic cardiomyopathy. Although revascularization may be considered in patients with extensive viable myocardium, patients with predominantly scar tissue should be treated medically or evaluated for heart transplantation. Among the many viability tests, noninvasive assessment of cardiac glucose use (as a marker of viable tissue) with F18-fluorodeoxyglucose (FDG) is considered the most accurate technique to detect viable myocardium. Cardiac FDG uptake has traditionally been imaged with positron emission tomography (PET). Clinical studies have shown that FDG-PET can accurately identify patients with viable myocardium that are likely to benefit from revascularization procedures, in terms of improvement of left ventricular (LV) function, alleviation of heart failure symptoms, and improvement of long-term prognosis. However, the restricted availability of PET equipment cannot meet the increasing demand for viability studies. As a consequence, much effort has been invested over the past years in the development of 511-keV collimators, enabling FDG imaging with single-photon emission computed tomography (SPECT). Because SPECT cameras are widely available, this approach may allow a more widespread use of FDG for the assessment of myocardial viability. Initial studies have directly compared FDG-SPECT with FDG-PET and consistently reported a good agreement for the assessment of myocardial viability between these 2 techniques. Additional studies have shown that FDG-SPECT can also predict improvement of LV function and heart failure symptoms after revascularization. Finally, recent developments, including coincidence imaging and attenuation correction, may further optimize cardiac FDG imaging (for the assessment of viability) without PET systems.     

55Co-EDTA for renal imaging using positron emission tomography (PET): a feasibility study

The feasibility of imaging renal function with 55Co-ethylene diamine tetraacetic acid (EDTA) and dynamic positron emission tomography was investigated. A group of normal Wistar rats was injected intravenously with 55Co-EDTA and underwent dynamic positron emission tomography (PET) imaging in order to study the biodistribution. The time-activity curves of the heart (blood pool), both kidneys, liver, and bladder were observed. In two animals, blood and urinary clearances of 55Co-EDTA were compared with those for 51Cr-EDTA. In one animal, unilateral reduction in kidney function was induced and the right/left ratio for the kidneys was determined. The time-activity curves showed that 55Co-EDTA cleared rapidly from the blood pool (heart), whereas prompt and high target-to-background ratios for both kidneys were obtained. The entire tracer was cleared from the renal parenchyma by urinary excretion and collection of the activity in the bladder. No specific activity uptake was noticed in any other organ or tissue. The clearances of 55Co-EDTA and 51Cr-EDTA in blood were not significantly different, showing that the nature of the M++ has no influence on the in vivo behavior of EDTA. 55Co can be produced easily by cyclotron irradiation and 55Co-EDTA is a promising physiological tracer for nephrological research using PET.     

The role of 18F-fluorodeoxyglucose positron emission tomography in gestational trophoblastic tumours: a pilot study

Purpose We conducted a pilot trial to evaluate the value of ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET) in gestational trophoblastic tumours (GTTs).Methods Patients with placental site trophoblastic tumour (PSTT), high-risk GTT (World Health Organisation score 8, disease onset at postpartum or greater than 6 months after antecedent pregnancy), metastatic GTT, recurrent/resistant GTT after chemotherapy, or post-molar GTT with unexplained abnormal -hCG regression and patients undergoing re-evaluation after salvage treatment were enrolled. PET was undertaken within 1 week after computed tomography (CT). Clinical impacts of additional PET were determined on a scan basis.Results A total of 14 patients were recruited. Sixteen PET scans were performed, with one patient having three serial studies. Benefits of additional PET were seen in 7 of 16 (43.8%) scans; these benefits included disclosure of chemotherapy-resistant lesions (n=2), exclusion of false-positive CT lesions (n=1), detection of an additional lesion not found by conventional imaging (n=1) in high-risk GTT at the start of primary chemotherapy, and confirmation of complete response to treatment for PSTT or to salvage therapy for recurrent/resistant GTT (n=3). On the other hand, in two instances there were false-negative PET findings, six scans yielded no benefit, and one showed an indeterminate lesion.Conclusion Our preliminary results suggest that ¹⁸F-FDG PET is potentially useful in selected patients with GTT by providing precise mapping of metastases and tumour extent upfront, by monitoring treatment response and by localising viable tumours after chemotherapy. A larger study is necessary to further define the role of ¹⁸F-FDG PET in GTT.     

Hypoxia positron emission tomography imaging with 18f-fluoromisonidazole

The importance of hypoxia in disease pathogenesis and prognosis is gathering increasing clinical significance and having a greater impact on patient management and outcome. Previous efforts to evaluate hypoxia have included the invasive assessment of hypoxia with immunohistologic and histographic oxygen probes. The emergence of new radiotracers has allowed noninvasive assessment of hypoxia, with the most extensively investigated and validated positron emission tomography radiotracer of hypoxia to date being (18)F-fluoromisonodazole ((18)F-FMISO). This review discusses the relevance and biology of hypoxia in cells and organ systems, and reviews the laboratory and clinical applications of (18)F-FMISO in oncology and noncancer disease states.     

Effect of different examination conditions on image quality and quantitative value of amyloid positron emission tomography using 18F-flutemetamol

Annals of Nuclear Medicine - The recommended start time for 18F-flutemetamol amyloid positron emission tomography (PET) examination is 60–120 min after 18F-flutemetamol injection,...     

Patient preparation for cardiac fluorine-18 fluorodeoxyglucose positron emission tomography imaging of inflammation

Although the number of clinical applications for fluorine-18 fluorodeoxyglucose (¹⁸F-FDG) cardiac positron emission tomography (PET) has continued to grow, there remains a lack of consensus regarding the ideal method of suppressing normal myocardial glucose utilization for image optimization. This review describes various patient preparation protocols that have been used as well as the success rates achieved in different studies. Collectively, the available literature supports using a high-fat, no-carbohydrate diet for at least two meals with a fast of 4-12 hours prior to ¹⁸F-FDG PET imaging and suggests that isolated fasting for less than 12 hours and supplementation with food or drink just prior to imaging should be avoided. Each institution should adopt a protocol and continuously monitor its effectiveness with a goal to achieve adequate myocardial suppression in greater than 80% of patients.     

Amyloid positron emission tomography and cognitive reserve

Alzheimer’s disease (AD) is characterized by a non-linear progressive course and several aspects influence the relationship between cerebral amount of AD pathology and the clinical expression of the disease. Brain cognitive reserve (CR) refers to the hypothesized capacity of an adult brain to cope with brain damage in order to minimize symptomatology. CR phenomenon contributed to explain the disjunction between the degree of neurodegeneration and the clinical phenotype of AD. The possibility to track brain amyloidosis (Aβ) in vivo has huge relevance for AD diagnosis and new therapeutic approaches. The clinical repercussions of positron emission tomography (PET)-assessed Aβ load are certainly mediated by CR thus potentially hampering the prognostic meaning of amyloid PET in selected groups of patients. Similarly, amyloid PET and cerebrospinal fluid amyloidosis biomarkers have recently provided new evidence for CR. The present review discusses the concept of CR in the framework of available neuroimaging studies and specifically deals with the reciprocal influences between amyloid PET and CR in AD patients and with the potential consequent interventional strategies for AD.     

18F-Fluoride positron emission tomography and positron emission tomography/computed tomography

(18)F-Fluoride is a positron-emitting bone-seeking agent, the uptake of which reflects blood flow and remodeling of bone. Assessment of (18)F-fluoride kinetics using quantitative positron emission tomography (PET) methods allows the regional characterization of lesions of metabolic bone diseases and the monitoring of their response to therapy. It also enables the assessment of bone viability and discrimination of uneventful and impaired healing processes of fractures, bone grafts and osteonecrosis. Taking advantage of the favorable pharmacokinetic properties of the tracer combined with the high performance of PET technology, static (18)F-fluoride PET is a highly sensitive imaging modality for detection of benign and malignant osseous abnormalities. Although (18)F-fluoride uptake mechanism corresponds to osteoblastic activity, it is also sensitive for detection of lytic and early marrow-based metastases, by identifying their accompanying reactive osteoblastic changes, even when minimal. The instant fusion of increased (18)F-fluoride uptake with morphological data of computed tomography (CT) using hybrid PET/CT systems improves the specificity of (18)F-fluoride PET in cancer patients by accurately differentiating between benign and malignant sites of uptake. The results of a few recent publications suggest that (18)F-fluoride PET/CT is a valuable modality in the diagnosis of pathological osseous conditions in patients also referred for nononcologic indications. (18)F-fluoride PET and PET/CT are, however, not widely used in clinical practice. The limited availability of (18)F-fluoride and of PET and PET/CT systems is a major factor. At present, there are not enough data on the cost-effectiveness of (18)F-fluoride PET/CT. However, it has been stated by some experts that (18)F-fluoride PET/CT is expected to replace (99m)Tc-MDP bone scintigraphy in the future.     

Florbetapir f-18: a histopathologically validated Beta-amyloid positron emission tomography imaging agent

Florbetapir F-18 is a molecular imaging agent combining high affinity for β-amyloid, pharmacokinetic properties that allow positron emission tomography (PET) imaging within a convenient time after dose administration, and the wide availability of the radionuclide fluorine-18. Florbetapir F-18 is prepared by nucleophilic radiofluorination in approximately 60 minutes with a decay-corrected yield of 20%-40% and with a specific activity typically exceeding 100 Ci/mmol. The florbetapir F-18 dissociation constant (K(d)) for binding to β-amyloid in brain tissue from Alzheimer's disease (AD) patients was 3.7 ± 0.3 nmol/L, and the maximum binding capacity (B(max)) was 8800 ± 1600 fmol/mg protein. Autoradiography studies have shown that florbetapir F-18 selectively binds to β-amyloid aggregates in AD patient brain tissue, and the binding intensity is correlated with the density of β-amyloid quantified by standard neuropathologic techniques. Studies in animals revealed no safety concerns and rapid and transient normal brain uptake (6.8% injected dose/g at 2 minutes and 1.9% injected dose/g at 60 minutes in the mouse). Florbetapir F-18 has been well-tolerated in studies of more than 2000 human subjects. Biodistribution studies in humans revealed predominantly hepatobiliary excretion. The whole body effective dose was 7 mSv from a dose of 370 MBq. The pharmacokinetic of florbetapir F-18 make it possible to obtain a PET image with a brief (10 minutes) acquisition time within a convenient time window of 30-90 minutes after dose administration. Clinical studies have demonstrated a clear correlation between in vivo PET imaging with florbetapir F-18 and postmortem histopathologic quantitation of β-amyloid in the brain.     

Diagnosis of a cardiac angiosarcoma by fluorine-18 fluordeoxyglucose positron emission tomography

European Radiology - Cardiac angiosarcoma is a rare tumour entity with a poor prognosis. Early detection is difficult but important for the further course of the disease. We report on a young...     

Diagnosis of a cardiac angiosarcoma by fluorine-18 fluordeoxyglucose positron emission tomography

Cardiac angiosarcoma is a rare tumour entity with a poor prognosis. Early detection is difficult but important for the further course of the disease. We report on a young patient with a tumour of unknown origin and dignity of the right atrium. Magnetic resonance imaging, CT and echocardiography were sufficient in localisation, but no statement on the dignity was possible. Furthermore, staging led to ambiguous results. Malignancy could be proved by fluorine-18 fluordeoxyglucose positron emission tomography, leading to early surgery. Histology revealed a poorly differentiated angiosarcoma.     

Cardiac positron emission tomography imaging

Cardiac positron emission tomography (PET) imaging has advanced from primarily a research tool to a practical, high-performance clinical imaging modality. The widespread availability of state-of-the-art PET gamma cameras, the commercial availability of perfusion and viability PET imaging tracers, reimbursement for PET perfusion and viability procedures by government and private health insurance plans, and the availability of computer software for image display of perfusion, wall motion, and viability images have all been a key to cardiac PET imaging becoming a routine clinical tool. Although myocardial perfusion PET imaging is an option for all patients requiring stress perfusion imaging, there are identifiable patient groups difficult to image with conventional single-photon emission computed tomography imaging that are particularly likely to benefit from PET imaging, such as obese patients, women, patients with previous nondiagnostic tests, and patients with poor left ventricular function attributable to coronary artery disease considered for revascularization. Myocardial PET perfusion imaging with rubidium-82 is noteworthy for high efficiency, rapid throughput, and in a high-volume setting, low operational costs. PET metabolic viability imaging continues to be a noninvasive standard for diagnosis of viability imaging. Cardiac PET imaging has been shown to be cost-effective. The potential of routine quantification of resting and stress blood flow and coronary flow reserve in response to pharmacologic and cold-pressor stress offers tantalizing possibilities of enhancing the power of PET myocardial perfusion imaging. This can be achieved by providing assurance of stress quality control, in enhancing diagnosis and risk stratification in patients with coronary artery disease, and expanding diagnostic imaging into the realm of detection of early coronary artery disease and endothelial dysfunction subject to risk factor modification. Combined PET and x-ray computed tomography imaging (PET-CT) results in enhanced patient throughput and efficiency. The combination of multislice computed tomography scanners with PET opens possibilities of adding coronary calcium scoring and noninvasive coronary angiography to myocardial perfusion imaging and quantification. Evaluation of the clinical role of these creative new possibilities warrants investigation.     

The new-generation positron emission tomography/computed tomography scanners: implications for cardiac imaging

Conclusion  The exceptionally rapid increase in the number of PET/CT scanners (often 3D only) for oncology may well facilitate an increase in cardiac PET imaging. However, there is only limited literature available as to how 3D acquisitions, especially with the new generation of scanners, will affect cardiac imaging. This situation will undoubtedly change very soon. Similarly, several aspects of CT-based attenuation correction for cardiac imaging remain to be investigated. Although, at the moment, 2D imaging with Ge-68 (or Cs-137) attenuation correction may remain the safest alternative for cardiac imaging, the new-generation PET/CT scanners hold great promise for the future of cardiac PET.