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

Obstructive uropathy refers to the condition of obstruction to urine flow from the kidney to the bladder. Such obstruction may be acute or chronic, complete or incomplete, and unilateral or bilateral. It has many diverse causes each with their own specific features and yet each producing similar disturbances to renal function and urine flow. This paper discusses the unique role of nuclear medicine techniques in the diagnosis and management of urinary tract obstruction in current urological practice.

The aim of evidence-based medicine is to integrate individual clinical expertise with the best available external clinical evidence from systematic research. The aim of this article is to introduce the concept of evidence based medicine and to review the evidence for applying cardiovascular nuclear medicine in various clinical settings. A systematic review is defined as a scientific technique to identify and summarize evidence on effectiveness of interventions and to allow the consistency of research. Different clinical applications of nuclear medicine procedures in cardiology have been reviewed. Radionuclide imaging techniques appear to be appropriate in risk assessment, prognosis and evaluation of therapy in patients after acute myocardial infarction. In patients with unstable angina, radionuclide testing is indicated in the identification of ischemia within the distribution of the "culprit" lesion or in remote areas. Exercise and pharmacological cardiac perfusion imaging are appropriate and useful in the diagnosis and prognosis of chronic coronary artery disease. Nuclear medicine procedures are also useful in the assessment of myocardial viability in patients with left ventricular dysfunction, in the assessment of interventions for the evaluation of patients after percutaneous transluminal coronary angioplasty and coronary artery bypass grafting. There has been rapid evolution in radionuclide imaging technologies and both the number and the complexity of choices for the clinician have increased. Further progress in technology and clinical applications of nuclear cardiology may be expected. The development of new instrumentation and of new agents will allow consistent progress and improve the state-of-art of nuclear cardiology. Thus, guidelines for the use of cardiac radionuclide imaging have been difficult to develop and apply. An evidence-based approach may be useful for the best use of nuclear medicine procedures in cardiovascular diseases.

Background: Therapeutic doses with Indium-111 (In-111)-DTPA-Octreotide are currently used in patients with somatostatin receptor positive tumours. It may result in tumour regression in some patients and this effect is ascribed to cell and receptor specific cytotoxicity by Auger or conversion electrons. Personnel being involved in this treatment may receive high radiation doses due to the emission of 173 keV and 247 keV photons. The aim of the present study was to assess the radiation dose to the personnel at different time intervals during treatment with Indium-111 Octreotide.

Methods: Five consecutive patients suffering from a neuroendocrine tumour were included in this dosimetry study. In total, 18 treatments with Indium-111 Octreotide have been given with a mean dose of 8000 MBq every three weeks. Three dosimeters (whole body, left and right hand) and a dose rate monitor were used to register doses and dose rates during labelling, administration and in-patient follow-up and whole body scintigraphy. These procedures were performed by a pharmacist, a nuclear physician and a technologist, respectively.

Results: The whole body dose received during the labelling procedure was 5 microSv. The mean total exposure time during administration, whole body scintigraphy and clinical follow-up was 47 minutes revealing a mean whole body dose of 45 microSv. The mean radiation dose to the hands was 60 microSv per treatment.

Conclusions: The radiation risk to staff members and technologists seems to be very low during in-patient treatments with high dose Indium-111 Octreotide. According to the safety regulations no special radiation protection measures or personal dosimetry is required.

Background: Circulating human thyroglobulin (hTG) measurements have a pivotal role in the management of patients affected by differentiated thyroid cancer (DTC). The present study was undertaken by employing a new developed high-sensitive hTG immunoradiometric assay to evaluate its diagnostic performance in patients affected by radically cured and relapsing DTC and to set the most appropriate cut-off point for DTC management.

Methods: We retrospectively selected 172 patients without signs of recurrence after primary treatment and 45 patients with recurrences from DTC. Serum samples were collected during l-thyroxine (T4) suppressive therapy (onT4) and 4 weeks after T4 withdrawal (offT4) and hTG measured by a specific high-sensitive IRMA assay (DYNOtest Tg-plus, BRAHMS Diagnostica GmbH, Berlin, Germany). Sera showing the presence of AbhTG or hTG-recovery less than 80% were excluded from the study. ROC curve analysis was performed to select the best cut-off levels and diagnostic performance of the marker evaluated.

Results: By using onT4 cut-off level of 0.2 ng/mL and offT4 cut-off level of 0.5 ng/mL we obtained a sensitivity/specificity/accuracy profile of 0.91/0.98/0.96 and 0.98/0.97/0.97, respectively. We found onT4-hTG false-negative results in 4 patient with local recurrence (n=2) or cervical lymph-node metastasis (n=2) while only 1 patient with local recurrence showed negative offT4-hTG. However, onT4 and offT4-hTG false-negative results were observed in 9 and 5 patients when 1.0 ng/mL cut-off level was employed.

Conclusions: On the basis of our data, we conclude that DYNOtest Tg-plus assay is very effective and accurate in the evaluation of patients with DTC.

Exercise renography is an investigative procedure used to visualize a renal functional disturbance of essential hypertension (EH). The exercise protocol was developed to intensify a renal functional abnormality observed in standing hypertensive patients, when it appeared that this disturbance was directly associated with EH. Clearance determinations during light ergometric exercise showed that the abnormal scintigraphic images of the exercise renogram result from a prominent contraction of glomerular filtration rate (GFR), while effective renal plasma flow (ERPF) remained comparatively stable. The results obtained at present with exercise renography and clearance determinations suggest that afferent-efferent glomerular vessel dysfunction disrupts the stable relationship between GFR and ERPF in EH. This relationship is severely disturbed, and most readily recognized, during exercise. It is suspected that this functional abnormality results in the activation of the renin-angiotensin axis. A particularly exciting consequence of this research is the recognition that scintigraphy permits recognition of a disruption of the stable relationship of GFR and ERPF. This opens the door to a broad area of research unrelated to EH, since initial results in renovascular disease and urinary tract obstruction indicate that the fixed relationship between GFR and ERPF can be disturbed in these and other diseases as well.

Antisense oligonucleotides, in short antisense, are small chains of nucleic acids capable to bind to cellular ribonucleic acid (RNA) by a hybridization mechanism. In vitro, antisense are widely used as reagents to detect or block specific RNA sequences. The use of antisense as in vivo diagnostic agents is attractive because it would bring molecular imaging at the level of gene expression. However, oligonucleotides are non-canonical radiopharmaceuticals and much progress is needed to adapt them to in vivo imaging. The requirements to reach this goal include improvements in radiosynthesis, stability, targeting, and specific and non-specific binding. They will be examined in this review together with the current achievements in the applications of antisense as nuclear medicine radiopharmaceuticals.

Monoclonal antibodies (MAbs), with high specificy and high affinity for their target antigens, can be utilized for delivery of agents such as radionuclides, enzymes, drugs, or toxins in vivo. However, the implementation of radiolabeled antibodies as "magic bullets" for detection and treatment of diseases such as cancer has required addressing several shortcomings of murine MAbs. These include their immunogenicity, sub-optimal targeting and pharmacokinetic properties, and practical issues of production and radiolabeling. Genetic engineering provides a powerful approach for redesigning antibodies for use in oncologic applications in vivo. Recombinant fragments have been produced that retain high affinity for target antigens, and display a combination of rapid, high-level tumor targeting with concomitant clearance from normal tissues and the circulation in animal models. An important first step was cloning and engineering of antibody heavy and light chain variable domains into single-chain Fvs (molecular weight, 25-27 kDa), in which the variable regions are joined via a synthetic linker peptide sequence. Although scFvs themselves showed limited tumor uptake in preclinical and clinical studies, they provide a useful building block for intermediate-sized recombinant fragments. Covalently linked dimers or non-covalent dimers of scFvs (also known as diabodies) show improved targeting and clearance properties due to their higher molecular weight (55 kDa) and increased avidity. Further gains can be made by generation of larger recombinant fragments, such as the minibody, an scFv-CH3 fusion protein that self-assembles into a bivalent dimer of 80 kDa. A systematic evaluation of scFv, diabody, minibody, and intact antibody (based on comparison of tumor uptakes, tumor:blood activity ratios, and calculation of an Imaging Figure of Merit) can form the basis for selection of combinations of recombinant fragments and radionuclides for imaging applications. Ease of engineering and expression, combined with novel specificities that will arise from advances in genomic and combinatorial approaches to target discovery, will usher in a new era of recombinant antibodies for biological imaging.

Antibody-based constructs genetically engineered from genes of diverse origin provide a remarkable opportunity to develop functional molecular imaging techniques and specific molecular targeted radionuclide therapies. Phage display libraries of antibody fragment genes can be used to select antibody-based constructs that bind any chosen epitope. A large naive human antibody-based library was used to illustrate binding of antibody constructs to a variety of common and unique antigens. Antibody-based libraries from hybridoma cells, lymphocytes from immunized humans or from mice and human antibody repertoires produced in transgenic mice have also been described. Several orders of magnitude of affinity enhancement can be achieved by random or site specific mutations of the selected binding peptide domains of the scFv. Affinities (Kd) as high as 10(-11) M (10 pM) for affinity-matured scFv have been documented. Such gene libraries thus offer an almost limitless variety of antibody-based molecular binding peptide modules that can be used in creative ways for the construction of new targeting agents for functional or molecular imaging and therapy.