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

Iodine-131 is the most specific radionuclide to follow up patients with differentiated thyroid cancer (DTC). However there are some aspects that should be considered if 131I whole body scintigraphy (131I WBS) is performed. 1) Several prior conditions, including a bTSH above 30 mU/l and an urinary iodine excretion below 100-150 micrograms/g Crea, should be fulfilled. 2) Only about two thirds of metastases from DTC accumulate iodine. Therefore, in addition to 131I WBS, there is a need for other nonspecific tracers such as 99mTc Tetrofosmin WBS, 99mTc Sestamibi WBS or F-18 FDG PET to detect also iodine negative recurrences or metastases. There new tracers, especially F-18 FDG PET have demonstrated a very high detection rate of iodine negative metastases with mostly low differentiation. 3) The sensitivity of 131I WBS depends on the administered dose. Whereas the sensitivity of a diagnostic 131I WBS (up to 185 MBq) is below 60%, the value for a post-therapeutic 131I WBS (after 3700-7400 MBq) increases up to 75%. This means that in case of elevated serum thyroglobulin, iodine positive metastases cannot be excluded until WBS after 131I therapy is performed. 4) In patients with elevated serum thyroglobulin and/or known metastases, who are scheduled for 131I treatment, the question arises whether a diagnostic 131I WBS should be performed and if so, which dose should be administered to avoid thyroid stunning. There is evidence in the literature that the dose for a pre-therapeutic diagnostic 131I WBS should not exceed 74 MBq. 5) Despite the high specificity of 131I WBS, several pitfalls of iodine accumulation in non-malignant diseases and malignancies of other origin than thyroid cancer should be taken into account.

Regulatory peptides are small, readily diffusable and potent natural substances with a wide spectrum of receptor-mediated actions in humans. High affinity receptors for these peptides are (over-) expressed in many neoplasms, and these receptors may represent, therefore, new molecular targets for cancer diagnosis and therapy. This review intends to give an overview of the peptide-based radiopharmaceuticals which are presently already commercially available or which are in advanced stages of their clinical testing so that their broader availability is anticipated soon. Physiologically, these peptides bind to and act through G protein-coupled receptors in the cell membrane. Historically, somatostatin analogs are the first class of receptor binding peptides having gained clinical application. 111In-DTPA-[D-Phe1]-octreotide is the first and only radiopeptide which has obtained regulatory approval in Europe and the United States to date. Extensive clinical studies involving several thousands of patients have shown that the major clinical application of somatostatin receptor scintigraphy is the detection and the staging of gastroenteropancreatic neuroendocrine tumors (carcinoids). In these tumors, octreotide scintigraphy is superior to any other staging method. However, its sensitivity and accuracy in other, more frequent neoplasms is limited. Radiolabeled vasoactive intestinal peptide (VIP) has been shown to visualize the majority of gastrointestinal adenocarcinomas, as well as some neuroendocrine tumors, including insulinomas (the latter being often missed by somatostatin receptor scintigraphy). Due to the outstanding diagnostic accuracy of the pentagastrin test in detecting the presence, persistence, or recurrence of medullary thyroid cancer (MTC), we postulated the expression of the corresponding [i.e., cholecystokinin (CCK-)-B] receptor type in human MTC. This receptor is also widely expressed on human small-cell lung cancer. Indeed, 111In-labeled DTPA derivatives of gastrin showed excellent targeting of CCK-B receptor expressing tissues in animals and patients. A variety of further peptide-based radioligands is currently under development. Summarizing, radiolabeled regulatory peptides have opened new horizons in nuclear oncology for diagnosis (and potential internal radionuclide therapy). Further work will probably reveal a multitude of novel potentially clinically useful peptide-based radioligands.

The autonomic innervation of the heart modifies most cardiac functions. Especially the heart rate and the force of contraction of myocytes are modulated by the autonomic nervous system. A number of specific neurotransmitters interact with receptors on post- and presynaptic binding sites regulating the complex electromechanical system of the heart. Disturbances at this interaction result in a variety of cardioneuropathies. The clinical manifestations can be mild and may only consist of sporadic arrhythmias without hemodynamic effects. In some cases however the autonomic dysfunction may be severe, e.g. in the acute phase of the Guillain-Barré syndrome and in advanced diabetic neuropathy. At present, the only available techniques to visualise and quantitate disbalanced innervation of the myocardium are scintigraphic modalities as single photon emission tomography (SPECT) and positron emission tomography (PET) with appropriate radiopharmaceuticals. These methods are reviewed with respect to their possible clinical application and to future developments.

With respect to further therapeutic options, whole-body 131I scintigraphy (WBS) is the most important functional imaging technique during treatment and follow-up of differentiated thyroid cancer. But in many patients, thyroid cancer tissue does not concentrate 131I and can therefore not be localized using WBS. In addition to morphologic techniques, which have a low specificity in many cases, other methods are necessary to localize tumor tissue in these patients. Besides 201Tl, which has been used initially as a tumor-seeking agent, sestamibi, tetrofosmin and 18F-DG for PET imaging have been evaluated in differentiated thyroid carcinoma. This paper summarizes the clinical impact of functional imaging with tracers besides 131I. In direct comparison, 18F-DG-PET has the highest sensitivity, which exceeds 80% in cases with negative WBS. If available, this method should be considered in all patients suffering from differentiated thyroid cancer with suspected recurrence and/or metastases, particularly in cases with elevated thyroglobulin values and negative WBS. But also 99mTc-labeled tracers can be used to detect tumor tissue with a sufficient sensitivity. In medullary thyroid cancer, which presents frequently with diagnostic difficulties, 111In-octreotide, 99mTc-(V)-DMSA, 131I/123I-mIBG, and anti-CEA can be used, in addition.

The genital tract is a complex anatomic region with overlapping endocrinologic, anatomic, and functional features. Nuclear medicine has value in examining functional aspects of reproductive and sexual function, ranging from testicular or cavernosal perfusion in the male, to fallopian tube transport in the female. Blood pool imaging has been helpful in detecting subclinical varicoceles. Proper understanding of the role that these tests play is important for their success and credibility.

Iodine deficiency and iodine deficiency disorders are still present in several parts of Europe. Sonography is neither specific in the diagnosis nor sensitive in the evaluation of the amount of autonomous thyroid tissue. Thyroidal autonomy is defined as a functional state of the thyroid and therefore only functional scintigraphic imaging, preferably performed with 99mTc-pertechnetate (99mTcO4-), will offer both high sensitivity and specificity in its diagnosis. Recently the cloning and characterisation of the Na+/I- symporter (NIS) offered a deeper understanding of iodine and pertechnetate uptake in the thyroid gland. Overexpression of the Na+/I- symporter following activation of the adenylate-cyclase-cAMP-cascade has been demonstrated in hot nodules, which gives for the first time an explanation for the enhanced iodine clearance of autonomous thyroidal tissue on a molecular level. The scintigraphic evaluation of thyroidal autonomy is performed both as a quantitative and qualitative thyroid scintigraphy, using a gamma camera fitted with an on-line computer system. A strong and linear correlation between the global 99mTc-pertechnetate thyroid uptake (TCTU) and 123I clearance has been recognised. Therefore TCTU-values can be used as a reliable equivalent of the iodine clearance in the evaluation of actual thyroid function. The clinical value of the TCTU in the diagnosis of thyroidal autonomy is limited because it represents iodine clearance of both normal and autonomous tissue. As a consequence scintigraphic diagnosis and quantification of autonomy can only be established if the global 99mTc-pertechnetate thyroid uptake under suppression (TCTUs) is determined. This method is sensitive in risk stratification of spontaneous or iodine induced hyperthyroidism, in the estimation of the target volume prior to radioiodine therapy independently of its distribution and in the evaluation of therapeutic success after definitive therapy.

Adrenocortical scintigraphy provides information concerning cortical function that is not readily available by other means. The ability to map differential adrenal cortical function has great clinical utility and demonstrable cost-effectiveness in the evaluation of adrenocortical disease and in distinguishing benign from malignant lesions in patients with incidentally discovered adrenal masses.

Monoclonal antibodies (MAbs) may be considered 'magic bullets' due to their ability to recognize and eradicate malignant cells. MAbs, however, have practical limitations for their rapid application in the clinics. The structure of antibody molecules can be engineered to modify functional domains such as antigen-binding sites and/or effector functions. Advances in genetic engineering have provided rapid progress in the development of new immunoglobulin constructs of MAbs with defined research and therapeutic application. Recombinant antibody constructs are being engineered, such as human-mouse chimeric, domain-dispositioned, domain-deleted, humanized and single-chain Fv fragments. Genetically-engineered antibodies differ in size and rate of catabolism. Pharmacokinetic studies show that the intact IgG (150 kD), enzymatically derived fragments Fab' (50 kD) and single chain Fv (28 kD) have different clearance rates. These antibody forms clear 50% from the blood pool in 2.1 days, 30 minutes and 10 minutes, respectively. Genetically-engineered antibodies make a new class of immunotherapeutic tracers for cancer treatment.

Positron emission tomography (PET) measurements of dopaminergic pathways have revealed several new insights into the role of dopamine in the pathophysiology and pharmacology of brain diseases such as Parkinson's disease (PD), dystonia and schizophrenia. PET studies of regional blood flow or metabolism identifies sites of regional pathology. Drug-induced changes in flow or metabolism indicate the function of dopamine-mediated pathways. Measurements of radioligand binding in vivo with PET reveals abnormalities associated with specific diseases and the actions of various drugs that affect the dopaminergic system. Finally, PET measurements of the uptake of analogues of levodopa provide clues to the function of dopamine pathways potentially important for diagnosis and treatment of disease like PD.

We have developed an in vivo selection system in which phage capable of selective homing to different tissues are recovered from a phage display peptide library following intravenous administration. Using this strategy, we have isolated several organ and tumor-homing peptides. We have shown that each of those peptides binds to different receptors that are selectively expressed on the vasculature of the target tissue. The tumor-homing peptides bind to receptors that are upregulated in tumor angiogenic vasculature. Targeted delivery of doxorubicin to angiogenic vasculature using these peptides in animal models decreased toxicity and increased the therapeutic efficacy of the drug. Vascular targeting may facilitate the development of other treatment strategies that rely on inhibition of angiogenesis and lead to advances in cancer treatment. Our technology is also likely to extend the potential for targeting of drugs, genes, and radionuclides in the context of many diseases.