German guidelines for brain tumour imaging by PET and SPECT using labelled amino acids

For the primary diagnosis of brain tumours, morphological imaging by means of magnetic resonance imaging (MRI) is the current method of choice. The complementary use of functional imaging by positron emitting tomography (PET) and single photon emitting computerized tomography (SPECT) with labelled amino acids can provide significant information on some clinically relevant questions, which are beyond the capacity of MRI. These diagnostic issues affect in particular the improvement of biopsy targeting and tumour delineation for surgery and radiotherapy planning. In addition, amino acid labelled PET and SPECT tracers are helpful for the differentiation between tumour recurrence and non-specific post-therapeutic tissue changes, in predicting prognosis of low grade gliomas, and for metabolic monitoring of treatment response. The application of dynamic PET examination protocols for the assessment of amino acid kinetics has been shown to enable an improved non-invasive tumour grading. The purpose of this guideline is to provide practical assistance for indication, examination procedure and image analysis of brain PET/SPECT with labelled amino acids in order to allow for a high quality standard of the method. After a short introduction on pathobiochemistry and radiopharmacy of amino acid labelled tracers, concrete and detailed information is given on the several indications, patient preparation and examination protocols as well as on data reconstruction, visual and quantitative image analysis and interpretation. In addition, possible pitfalls are described, and the relevant original publications are listed for further information.     

用于肿瘤代谢显像的几种放射性标记氨基酸

随着代谢显像的广泛应用,放射性标记氨基酸越来越引起临床关注。与18F-FDGPET显像相比,氨基酸显像的优点在于其受炎症的影响较小。对于脑肿瘤,氨基酸代谢显像具有较高的诊断价值。对大多数其它类型的肿瘤而言,尽管凭现有资料尚不能得出最终结论,但其总体可行性已得到充分显示。因此,仍有必要进行经过精心设计的更大样本病例的研究。本文着重描述了11C-蛋氨酸(MET)、11C-酪氨酸(TYR)、123I-甲基酪氨酸(IMT)的基本特性和临床应用。     

Simple automatic quality control for radiolabeled gases for PET

Quality control of routine radiopharmaceutical preparations of carbon monoxide, carbon dioxide and oxygen is necessary. Still, this simple task is compromised by the high demand for gas chromatograph (GC) time in a busy laboratory. Frequent production of such materials at essentially random intervals requires a dedicated radio-GC system. We report a simple, inexpensive and automatic routine quality control approach that is continuously available independently of the main laboratory instrument and provides the same accuracy.     

Indication for different mechanisms of kidney uptake of radiolabeled peptides.

Nephrotoxicity due to renal reabsorption of radiolabeled peptides limits the tumor dose in peptide receptor radiotherapy (PRRT). Therefore, we evaluated the ability of several agents to inhibit the renal accumulation of different radiopeptides. METHODS: Male Wistar rats (4 per group) were injected intravenously with 1 MBq of (111)In-labeled octreotide (OCT), minigastrin (MG), bombesin (BOM), or exendin (EX), together with a potential inhibitor of renal uptake (lysine [Lys], poly-glutamic acid [PGA], and Gelofusine [GF], a gelatin-based plasma expander) or phosphate-buffered saline as a control. Organ uptake at 20 h after injection was determined as the percentage of injected activity per gram (%IA/g). Lys, PGA, and GF were also combined to determine whether an additive effect could be obtained. The localization of the peptides in the kidneys was investigated by autoradiography using a phosphor imager. RESULTS: OCT accumulation in the kidney was inhibited by Lys and GF (40.7%-45.1%), whereas PGA was ineffective. On the other hand, renal uptake of BOM, MG, and EX was inhibited by PGA and GF (15.4%-85.4%), whereas Lys was ineffective. The combination of GF and Lys showed additive effects in inhibiting OCT uptake, whereas PGA and GF had additive effects for the inhibition of EX uptake. The amount of kidney uptake correlated with the number of charged amino acids. All radiopeptides were localized in the renal cortex, as indicated by autoradiography. CONCLUSION: Inhibition of renal accumulation of the radiopeptides tested could be achieved by either Lys or PGA but not by both at the same time, suggesting 2 different uptake mechanisms. The differences in renal accumulation of radiopeptides may be related to the number of charges of a molecule. GF is the only compound that inhibited renal accumulation of all radiopeptides tested. Additional experiments are needed to further elucidate these findings and to optimize inhibition of renal accumulation of radiopeptides to reduce the kidney dose in PRRT.     

Molecular imaging of gene expression and protein function in vivo with PET and SPECT

Molecular imaging is broadly defined as the characterization and measurement of biological processes in living animals, model systems, and humans at the cellular and molecular level using remote imaging detectors. One underlying premise of molecular imaging is that this emerging field is not defined by the imaging technologies that underpin acquisition of the final image per se, but rather is driven by the underlying biological questions. In practice, the choice of imaging modality and probe is usually reduced to choosing between high spatial resolution and high sensitivity to address a given biological system. Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) inherently use image-enhancing agents (radiopharmaceuticals) that are synthesized at sufficiently high specific activity to enable use of tracer concentrations of the compound (picomolar to nanomolar) for detecting molecular signals while providing the desired levels of image contrast. The tracer technologies strategically provide high sensitivity for imaging small-capacity molecular systems in vivo (receptors, enzymes, transporters) at a cost of lower spatial resolution than other technologies. We review several significant PET and SPECT advances in imaging receptors (somatostatin receptor subtypes, neurotensin receptor subtypes, alpha(v)beta(3) integrin), enzymes (hexokinase, thymidine kinase), transporters (MDR1 P-glycoprotein, sodium-iodide symporter), and permeation peptides (human immunodeficiency virus type 1 (HIV-1) Tat conjugates), as well as innovative reporter gene constructs (herpes simplex virus 1 thymidine kinase, somatostatin receptor subtype 2, cytosine deaminase) for imaging gene promoter activation and repression, signal transduction pathways, and protein-protein interactions in vivo.     

PET and SPECT in low-grade glioma

Low-grade gliomas (LGG) account for 30-40% of all gliomas and are primarily treated with surgery. Since both timing and use of other oncological treatments in LGG are a matter of controversy, there has been a constantly increasing demand to characterize these often slowly growing neoplasms with functional imaging methods, such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT). PET and SPECT yield information on growth rate and heterogeneity of LGG and are especially useful in follow-up since metabolic changes tend to precede structural changes detected with structure-based imaging methods. Furthermore, for planning of LGG surgery or radiotherapy coregistration of functional images with CT and MRI is invaluable. This is increasingly performed with a new generation of hybrid scanners with integrated PET or SPECT and CT.     

Molecular imaging (SPECT and PET) in the evaluation of patients with movement disorders

In this article the role of molecular imaging with SPECT and PET in patients with movement disorders is reviewed. It is mentioned that SPECT and PET imaging with cocaine analogues ((123)I-beta-CIT,(123)I-FP-CIT, (18)F-DOPA), radioligands labeling the presynaptic dopamine transporters, is of value for the differentiation of patients with PD or Parkinson-plus syndromes with individuals with essential tremor. In addition the clinical impact of this procedure, the role of molecular imaging in the preclinical diagnosis and in the follow-up of patients with PD, as well as, in the differential diagnosis between Alzheimer's disease and Lewy-body dementia, is evaluated. Finally, the clinical impact of (123)I-IBZM-SPECT imaging, a radiopharmaceutical which labels the postsynaptic D(2) receptors and the discrimination between idiopathic PD and Parkinson-plus syndromes (multiple system atrophy, progressive supranuclear palsy and corticobasal ganglia degeneration), is mentioned.     

An introduction to PET and SPECT neuroreceptor quantification models.

PET and SPECT using appropriate radioligands allow imaging of certain critical components of neurotransmission such as presynaptic transporters and postsynaptic receptors in living human brains. PET and SPECT data are commonly analyzed by applying tracer kinetic models. These modeling approaches assume a compartmental system and derive the outcome measure called the binding potential, which reflects the densities of transporters or receptors in a brain region of interest. New models are often noninvasive in that they do not require arterial blood sampling. In this review, the concept and principles of tracer kinetic modeling are introduced and commonly used PET and SPECT neuroreceptor quantification models are discussed.     

SPECT and PET in the evaluation of coronary artery disease.

Cardiac positron emission tomography (PET) is an accurate method for assessing myocardial perfusion and metabolism in the evaluation of coronary heart disease. PET allows more accurate detection of myocardial ischemia than single photon emission tomography (SPECT). In addition, PET has higher spatial resolution and allows attenuation correction and the quantification of various physiologic parameters. PET with 2-(fluorine-18) fluoro-2-deoxy-D-glucose is considered the standard of reference for predicting improvement in regional or global left ventricular function after revascularization by identifying hibernating viable myocardium that shows diminished perfusion and preserved metabolism. Other less commonly used clinical applications of cardiac PET include assessment of myocardial oxygen consumption and fatty acid metabolism. The use of PET in myocardial imaging is expected to increase in the near future with the regional distribution of positron-emitting radiotracers and the emergence of relatively low-cost PET systems.     

SPECT imaging of pulmonary emboli with radiolabeled thrombus-specific imaging agents

The safe and accurate diagnosis of acute pulmonary embolism (PE) remains challenging, and many PE-related deaths still occur before the detection of PE. Current techniques detect PE as "negative images," ie, the absence of contrast or downstream perfusion. There would be advantages to obtaining "positive images" of PE, by targeting imaging agents to components that are present primarily on thromboemboli. In addition to providing alternative means of diagnosing acute PE, they would also enable acute PE to be distinguished from other types of pulmonary arterial obstruction, such as unresolved intravascular defects attributable to previous PE. Positive images of PE require imaging agents to bind onto target antigens that are present predominantly on thromboemboli. The "D dimer" regions of polymerized fibrin are present in high concentrations on thromboemboli and are sufficiently accessible to binding. (99m)Tc-lableled anti-D-dimer deimmunized monoclonal antibody Fab' fragments (DI-DD-3B6/22-80B3) bind specifically to thromboemboli, with a thrombus: blood labeling ratio that allows scintigraphic detection. Another thrombus-specific imaging agent is (99m)Tc-labeled apcitide, a synthetic peptide that binds with a high affinity and specificity to the glycoprotein IIb/IIIa receptor on the membrane of activated platelets. Both of these agents have enabled the detection of lower extremity deep vein thrombi by planar scintigraphy. However, even highly radiolabeled PEs are difficult to distinguish by planar scintigraphy from the large blood pool in the heart and lungs. The spatial and contrast resolution inherent to single-photon emission computed tomography (SPECT) scanning allow the in situ imaging of pulmonary emboli that have been bound by radiolabeled thrombus-specific imaging agents. Preliminary trials in humans with acute PE have shown that the emboli can be detected after intravenous administration of (99m)Tc-lableled anti-D dimer, followed by SPECT scanning. Although clinical results are still preliminary, it appears that imaging of pulmonary emboli with SPECT, after administration of radiolabeled thrombus-specific antibody fragments, is accurate and clinically feasible.     

Synthesis and evaluation of radiolabeled piperazine derivatives of vesamicol as SPECT agents for cholinergic neurons

To diagnose and investigate neurodegenerative diseases affecting cholinergic neuron density, piperazine derivatives of vesamicol were synthesized and evaluated. Previously, we reported that trans-5-iodo-2-hydroxy-3-[4-phenylpiperazinyl] tetralin (DRC140, 1) possessed high selectivity for vesicular acetylcholine transporter (VAChT). In present study of the effect of alkyl substituents, we observed that the introduction of a methyl group into the ortho or meta positions of the phenyl group of 1 increased affinity for VAChT. trans-5-Iodo-2-hydroxy-3-[4-[2-methylphenyl] piperazinyl]tetralin (2) displayed high affinity and specificity for VAChT. The regional distributions of radioactivity in the rat brain correlated well with known patterns of central cholinergic innervation. [(123)I]2 is a potentially useful compound for SPECT imaging.     

PET and SPECT investigations in Alzheimer's disease

Zusammenfassung Nuklearmedizin bietet bei der Erfassung und Beurteilung eines dementiellen Prozesses eine Vielzahl von Untersuchungsmöglichkeiten. Anhand des Morbus Alzheimer (DAT) werden in dem vorliegenden Artikel neben einer kurzen Schilderung der zur Verfügung stehenden Methoden die verschiedenen nuklearmedizinisch relevante Fragestellungen angeführt, zu deren Beantwortung die funktionelle Bildgebung Informationen liefern kann. Durch den Einsatz bestimmter, standardisierter Auswerteverfahren wie statistical parametric mapping (SPM) ist es möglich, entscheidende Hinweise zur Diagnose und Differenzialdiagnose der DAT zu erlangen. In Zukunft werden, insbesondere bei einer Verfügbarkeit neuroprotektiver Therapien, eine möglichst frühe Diagnosestellung und die Erfassung von Risikofaktoren sowie die Möglichkeit einer Verlaufsbeobachtung in den Mittelpunkt des Interesses und in das Zentrum nuklearmedizinischer Untersuchungen rücken. Vor allem für diese Anforderungen ist neben der qualitätsvollen Untersuchung von zerebraler Perfusion und Glukosestoffwechsel eine Weiterentwicklung spezieller Liganden v. a. das cholinerge System betreffend und eine Markierung der Amyloidplaques vonnöten.

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