The quarterly journal of nuclear medicine : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR)最新文献

The developing role and use of diagnostic imaging continue to emerge as disease management paradigms are refined and clinical guidelines are employed more often. Health technology assessment, HTA (also known as health care technology assessment), is fundamentally a form of policy research. By formulating effective HTA, the short- and long-term effects of health care technology are studied in a systematic and multidisciplinary way. The fundamental aim of all HTA is to assist those individuals and organizations who stand to benefit from a new health technology (patients), those who will apply the technology (providers), and those who will pay for it (payers) to make better decisions about the technology they utilize by supplying information that is of a high scientific standard and population-based. Effective HTA is especially useful to health care providers, payers, professional groups in health care, manufacturers, political decision-makers and the general public or consumers of health care technology because it represents a process through which effective technology can be identified and ineffective technology can be understood in the context of its limitations. HTA is a multidisciplinary undertaking requiring combined expertise in clinical medicine, epidemiology, biostatistics, bioengineering, health economics, administration, psychology, sociology, ethics and legal science. Additionally, the experiences and opinions of health technology users and consumers of health care (especially patient advocacy groups) are needed to form an overall accurate understanding of the technology under review.

Background: The purpose of this study was to assess if breast cancer screening using sestamibi scintimammography (SSMM) in conjunction with mammography (MM) is cost effective in avoiding biopsies in healthy patients.

Methods: Quantitative decision tree sensitivity analysis was used to compare the conventional MM alone strategy (strategy A) with two decision strategies for screening with SSMM; SSMM after an indeterminate mammogram (strategy B) or SSMM after both a positive and an indeterminate mammogram (strategy C). Cost effectiveness was measured by calculating the expected cost per patient and the average life expectancy per patient for baseline values as well as over a range of values for all of the variables of each strategy.

Results: Based on Medicare reimbursement values, strategies B and C showed a cost savings of $9 and $20 per patient respectively as compared to strategy A. This translates into respective savings of $189 and $420 million per year assuming 21 million females undergo screening each year. Strategies B and C did however have a loss of mean life expectancy of 0.000178 and 0.000222 years respectively as compared to strategy A due to interval progression of breast cancer in a small number of women. Strategies B and C significantly lowered the number of biopsies performed on healthy patients in the screening population by 750,063 and 1,557,915 biopsies respectively as compared to strategy A.

Conclusions: These results quantitatively verify the potential utility of using SSMM in avoiding unnecessary biopsies.

The future of nuclear medicine procedures, as understood within our current economic climate, depends upon its ability to provide relevant clinical information at similar or lower comparative costs. With an ever-increasing emphasis on cost containment, outcome assessment forms the basis of preserving the quality of patient care. Today, outcomes assessment encompasses a wide array of subjects including clinical, economic, and humanistic (i.e., quality of life) outcomes. For nuclear cardiology, evidence-based medicine would require a threshold level of evidence in order to justify the added cost of any test in a patient's work-up. This evidence would include large multicenter, observational series as well as randomized trial data in sufficiently large and diverse patient populations. The new movement in evidence-based medicine is also being applied to the introduction of new technologies, in particular when comparative modalities exist. In the past 5 years, we have seen a dramatic shift in the quality of outcomes data published in nuclear cardiology. This includes the use of statistically rigorous risk-adjusted techniques as well as large populations (i.e., > 500 patients) representing multiple diverse medical care settings. This has been the direct result of the development of multiple outcomes databases that have now amassed thousands of patients worth of data. One of the benefits of examining outcomes in large patient datasets is the ability to assess individual endpoints (e.g., cardiac death) as compared with smaller datasets that often assess combined endpoints (e.g., death, myocardial infarction, or unstable angina). New technologies for the diagnosis of coronary artery disease have contributed to the rising costs of care. In the United States and in Europe, costs of care have risen dramatically, consuming an ever-increasing amount of available resources. The overuse of diagnostic angiography often leads to unnecessary revascularization that does not lead to improvement in outcome. Thus, the potential exists that stress SPECT imaging, a highly effective diagnostic tool, could effect substantial change in reducing inappropriate use of an invasive procedure resulting in cost effective cardiac care. A synthesis of current economic evidence in gated SPECT imaging will be presented. In conclusion, a current state of the evidence review is presented on the clinical and economic data using nuclear cardiology imaging.

Background: Somatostatin receptor imaging with 111In-pentetreotide is widely accepted as an essential step in the management of patients affected by neuroendocrine tumours of the gastro-entero-pancreatic tract. Many data are already available on the high sensitivity of this technique.

Methods: We present a review of the published data together with the results of a study involving 253 patients submitted to somatostatin receptor imaging in three Italian hospitals. The patients were divided into two groups treated with different acquisition and processing protocols.

Results: The overall sensitivity was as high as (169/176) 96% in both groups, while the specificity was higher in the group in which semi-quantitative evaluation of somatostatin receptor density was performed: (23/26) 88% vs (39/51) 76%. The use of this method is recommended to increase the specificity of 111In-pentetreotide imaging.

Conclusions: Our results with somatostatin receptor imaging in neuroendocrine tumours of the gastro-entero-pancreatic tract demonstrate that all figures of merit are excellent when imaging is accurately performed and analysed by experienced operators.

In vitro data have demonstrated a high amount of receptors for various hormones and peptides on malignant cells of neuroendocrine origin. Among these, binding sites for members of the SST-family (hSSTR1-5) are frequently found, and their expression has led to therapeutic and diagnostic attempts to specifically target these receptors. Receptor scintigraphy using radiolabeled peptide ligands has proven its effectiveness in clinical practice. In addition, initial results have indicated a clinical potential for receptor-targeted radiotherapy. Based on somatostatin (SST) receptor (R) recognition, the novel radiopharmaceuticals 111In/90Y-DOTA-lanreotide developed at the University of Vienna as well as 111In/90Y-DOTA-DPhe1-Tyr3-octreotide (NOVARTIS) both have provided promising data for diagnosis and treatment of hSSTR-positive tumors. SSTR scintigraphy using 111In-DTPA-DPhe1-octreotide has a high positive predictive value for the vast majority of neuroendocrine tumors and has gained its place in the diagnostic work-up as well as follow-up of patients. We have used 111In-DOTA-lanreotide scintigraphy in 166 patients since 1997 and have seen positive results in 93% of patients. In 42 patients with neuroendocrine tumors comparative data were obtained. As opposed to 111In-DTPA-DPhe1-octreotide and 111In-DOTA-DPhe1-Tyr3-octreotide, discrepancies in the scintigraphic results were seen in about one third of patients concerning both the tumor uptake as well as tumor lesion detection. Initial results both with 90Y-DOTA-lanreotide as well as 90Y-DOTA-DPhe1-Tyr3-octreotide has pointed out the clinical potential of radionuclide receptor-targeted radiotherapy. This new therapy could offer palliation and disease control at a reduced cost. The final peptide therapy strategy is most probably cheaper than conventional radiotherapies or prolonged chemotherapies. Overall, receptor-mediated radiotherapy with 90Y-DOTA-lanreotide/90Y-DOTA-DPhe1-Tyr3-octre otide might also be effective in patients refractory to conventional strategies.

Neuroendocrine tumors are characterized by the expression of different peptides and biogenic amines. These rare tumors tend to grow slowly and are notoriously difficult to localize, at least in the early stages. Surgical removal is the only definitive therapeutic option for neuroendocrine tumors and relief from hyperfunctional status. The effectiveness of surgical treatment is invariably dependent upon the complete surgical excision of all tumor tissue, because microscopic and occult disease not readily seen by the surgeon may remain in situ, leading to shortened survival. Therefore, pre- and intraoperative localization of the primary as well as of metastatic tumors is of utmost importance. Radioguided surgery (RGS) is an intraoperative technique that enables the surgeon to localize radiolabelled tissue based on the characteristics of the various tissues. Concerning gastroenteropancreatic tumors (GEP), intraoperative gamma probe examination is able to reveal small tumor sites accumulating (111In-DTPA-D-Phe1)-pentetreotide more efficiently (> 90%) than somatostatin receptor scintigraphy (68%-77%), because lesions with a size smaller than 5 mm in greatest dimension could be identified. Furthermore, RGS identified 57% more lesions when compared to the "palpating finger" of the surgeon. In medullary thyroid cancer (MTC), surgical removal of the tumor is the first and most efficient treatment of the disease. Persistent or increasing serum calcitonin and carcinoembryonic antigen (CEA) levels imply tumor recurrence after thyroid ablation. For imaging recurrent MTC many radiopharmaceuticals have been used to visualize tumor sites, but none of them has shown excellent sensitivity. Preoperative somatostatin receptor scintigraphy and intraoperative RGS in patients with recurrent MTC demonstrate only part of the tumor sites and cannot visualize small tumor sites (less than 10 mm). In comparison, RGS using 99mTc(V)-DMSA detects metastases with a size of 5 mm in diameter, whereas the "palpating finger" of the surgeon localized metastases with a size of more than 1 cm in diameter. In patients with recurrent MTC, intraoperative gamma probe examination is able to localize over 30% more tumor lesions when compared with conventional preoperative imaging modalities and surgical findings. MIBG scintigraphy is the most sensitive technique for the detection and staging of neuroblastoma (sensitivity 92%; specificity nearly 100%). Intraoperative RGS with iodine labelled MIBG has been developed to improve the definition of tumor limits or to localize small, nonpalpable tumors. Comparison of 123I- and 125I-labelled MIBG revealed a sensitivity of 91% and 92%, respectively; the specificity of 125I (85%) was significantly higher than that of 123I (55%). In addition to scintigraphy of the adrenal glands by precusors of adrenal hormones, imaging with a radiolabelled somatostatin analogue is possible; however, (111In-DTPA-D-Phe1)-pentetreotide is not specific for any adren

Positron emission tomography (PET) performed with various radiolabelled compounds facilitates the study of tumor biochemistry. If the tumor uptake of an administered tracer is greater than that of surrounding normal tissue, it is also possible to localize the tumor. In initial studies, 18F-labeled deoxyglucose (FDG) was attempted to visualize the tumors, since this tracer had been successfully used in oncology, reflecting increased glucose metabolism in cancerous tissue. However, this tracer was not to any significant degree taken up by the neuroendocrine tumors. Instead, the serotonin precursor 5-hydroxytryptophan (5-HTP) labeled with 11C was used and showed an increased uptake and irreversible trapping of this tracer in carcinoid tumors. The uptake was selective and the resolution so high that we could detect more liver and lymph node metastases with PET than with CT or octreotide scintigraphy. One problem was, however, the high renal excretion of the tracer producing streaky artifacts in the area of interest. Using the decarboxylase inhibitor carbidopa, given as peroral premedication, the renal excretion decreased 6-fold and at the same time the tumor uptake increased 3-fold, hence improving the visualization of the tumors. When patients were followed during treatment with PET using 5-HTP as a tracer, a > 95% correlation between changes in urinary 5-hydroxyindoleacetic acid (U-5-HIAA) and changes in the transport rate constant for 5-HTP was observed. Thus, PET can be used to monitor treatment effects. Elevation of U-5-HIAA is considered to be uncommon in endocrine pancreatic tumors (EPTs). Initially, 11C-labeled L-DOPA was attempted as another amine important in the APUD system. With L-DOPA about half of the EPTs, mainly functioning tumors, could be detected. Recently, 5-HTP was explored as a universal tracer also for EPT and foregut carcinoids, extending the PET-examination to both thorax and abdomen (whole-body PET-examination). With this method we were able to visualize small lesions in the pancreas and thorax (e.g. ACTH-producing bronchial carcinoids) not detectable by any other method including octreotide scintigraphy, MRI and CT. Several other tracers have been investigated, e.g. the monoamineoxidase (MAO-A) inhibitor harmine with promising results in non-functioning EPTs. We are currently exploring a wide range of biochemical systems, including enzymes and receptors, both for neurotransmitters and for peptides and proteins in in vitro assays with the potential to use some of the developed tracers for in vivo visualization and tumor biological studies. In conclusion, PET is a valuable tool in the diagnosis of neuroendocrine tumors. It can detect small lesions in the thorax and abdomen not detected by other methods, which has been of great value preoperatively in several cases. It detects more lesions in the liver and lymph nodes than other methods and furthermore, it can be used to monitor treatment effects.

Neuroendocrine tumours (NETs) often have a good prognosis and have peculiar biological characteristics, among which the ability to produce and release biologically active substances. Hypersecretion of hormones, biogenic amines or growth factors often cause severe syndromes that are very debilitating. Now sensitive assays for the measurement of these substances have been developed and this has improved the possibility of patient follow-up by means of in vitro examinations. The decision about which in vitro examination to be utilised for NET management is very difficult because of the NET low incidence, the very large number of measurable hormones, the difficulty or low patient compliance for some diagnostic tests. In this review we describe the most useful laboratory tests for determining the diagnosis of NET, their prognostic significance and the clinical value of specific marker evaluation in the follow-up of the NET patient. Particular consideration has been given to biomarkers for gastroenteropancreatic and sympatho-adrenal system tumours and for prostate and breast cancers with neuroendocrine differentiation.