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Introduction: Steroid hormones like androgens play an important role in the development and maintenance of several brain functions. Androgens can act through androgen receptors (AR) in the brain. This study aims to demonstrate the feasibility of positron emission tomography (PET) with 16β-[(18)F]fluoro-5α-dihydrotestosterone ([(18)F]FDHT) to image AR expression in the brain., Methods: Male Wistar rats were either orchiectomized to inhibit endogenous androgen production or underwent sham-surgery. Fifteen days after surgery, rats were subjected to a 90-min dynamic [(18)F]FDHT PET scan with arterial blood sampling. In a subset of orchiectomized rats, 1mg/kg dihydrotestosterone was co-injected with the tracer in order to saturate the AR. Plasma samples were analyzed for the presence of radioactive metabolites by radio-TLC. Pharmacokinetic modeling was performed to quantify brain kinetics of the tracer. After the PET scan, the animals were terminated for ex-vivo biodistribution., Results: PET imaging and ex vivo biodistribution studies showed low [(18)F]FDHT uptake in all brain regions, except pituitary. [(18)F]FDHT uptake in the surrounding cranial bones was high and increased over time. [(18)F]FDHT was rapidly metabolized in rats. Metabolism was significantly faster in orchiectomized rats than in sham-orchiectomized rats. Quantitative analysis of PET data indicated substantial spill-over of activity from cranial bones into peripheral brain regions, which prevented further analysis of peripheral brain regions. Logan graphical analysis and kinetic modeling using 1- and 2-tissue compartment models showed reversible and homogenously distributed tracer uptake in central brain regions. [(18)F]FDHT uptake in the brain could not be blocked by endogenous androgens or administration of dihydrotestosterone., Conclusion: The results of this study indicate that imaging of AR availability in rat brain with [(18)F]FDHT PET is not feasible. The low AR expression in the brain, the rapid metabolism of [(18)F]FDHT in rats and the poor brain penetration of the tracer likely contributed to the poor performance of [(18)F]FDHT PET in this study., (Copyright © 2015 Elsevier Inc. All rights reserved.)

In the recent years, many radiopharmaceuticals have been described for the diagnosis of inflammatory chronic diseases. Several peptides, receptor ligands and monoclonal antibodies have been radiolabelled, allowing in-vivo visualization of inflammatory processes at a cellular and molecular level. The labelling of cytokines such as interleukin-1, interleukin-2, interleukin-12 and MCP-1 has facilitated the identification of inflamed synovia in patients with rheumatoid arthritis, active Crohn's disease, vulnerable atherosclerotic plaques and other targets. The possibility of using monoclonal antibodies against TNF-α, CD2, CD3, CD4 and anti-selectin has not only allowed the localization of inflamed sites but had also a significant impact in helping the selection of patients who can benefit from biological therapies. Regarding radiolabelled peptides, it is important to highlight the increasing use of somatostatin analogues targeting somatostatin receptors in inflammatory diseases, particularly for rheumatoid arthritis, Sjögren syndrome and autoimmune thyroid diseases. In the present review we describe the state of the art of SPECT radiopharmaceuticals to image chronic inflammatory diseases.

Unlabelled: Given the importance of angiogenesis for a tumor's survival and growth, several therapeutic strategies rely on the selective inhibition of angiogenesis and the destruction of existing tumor vasculature. These strategies raise the need for a noninvasive tool to evaluate tumor vasculature. We describe the radiosynthesis and evaluation of an imaging tracer that specifically binds tumor subendothelial collagen and thereby images tumor vasculature., Methods: (99m)Tc-tricarbonyl was prepared and labeled with His-collagen-binding adhesion protein 35 (CNA35). After in vitro specificity testing, in vivo biodistribution and dosimetric studies were performed in healthy nude mice via planar imaging. (99m)Tc-(CO)(3) His-CNA35 was evaluated for in vivo imaging of tumor vasculature in a HT29 colorectal carcinoma xenograft., Results: The labeling procedure yielded a compound with 95%-99% radiochemical purity and good in vitro stability. An in vitro binding test confirmed specificity and functionality. (99m)Tc-(CO)(3) His-CNA35 rapidly cleared from the blood and predominantly accumulated in the kidneys and liver. The effective dose for a proposed single injection of 500 MBq of (99m)Tc-(CO)(3) His-CNA35 is 3.70 mSv per organ or 2.01 mSv/g of tissue. Tumors were successfully visualized, and uptake correlated with ex vivo immunohistochemical staining of tumor vasculature., Conclusion: (99m)Tc-(CO)(3) His-CNA35 may be a useful radioligand for the in vivo detection of tumor vasculature through subendothelial collagen binding. A noninvasive method of imaging tumor vasculature that could provide a reliable assessment of tumor vasculature would allow evaluation of the effectiveness of commonly used antiangiogenic therapies and determination of their optimal dosing and scheduling.

The aim of this study was to define, retrospectively, the utility to perform (99m)Tc-EDDA/HYNIC-Tyr3-octreotide ((99m)Tc-EDDA/HYNIC-TOC) scan in patients with NET. We studied 50 consecutive patients affected by different types of NET and divided in two groups. Group 1: 34 patients with known lesions in which (99m)Tc-EDDA/HYNIC-TOC was performed for staging, characterisation or to choose the appropriate treatment. Group 2: 16 patients suspected of having NET or in follow up after surgery. Patients were injected with 370 MBq of (99m)Tc-EDDA/HYNIC-Tyr3-octreotide and whole-body and SPET images acquired 2-3 hours after injection. Overall, 29 patients (58%) had a positive scan, with a sensitivity, specificity and accuracy of 70.3%, 76.9% and 72%, respectively (78.1%, 50% and 76.5%, in group 1 and 20%, 81.2%, 62.5% in group 2). In patients from group 1 (99m)Tc-HYNIC-TOC scintigraphy showed a concordance of 68% with another imaging procedure and in 9 patients revealed a greater number of lesions. In the second group, false negative results were especially found in patients with medullary thyroid cancer with negative radiological findings and elevated calcitonin. In conclusion, (99m)Tc-EDDA/HYNIC-TOC is highly indicated for in vivo histological characterization of known NET lesions, previously identified by other imaging modalities or biopsy, to plan appropriate therapy especially for patients with inoperable disease. In patients with only biochemical suspicion of NET and in those with negative markers, this scintigraphy does not significantly modify the clinical management.

Tumor cells are characterized by an increased rate of glucose consumption and glycolysis. This increased glucose consumption leads to tumor acidification, which represents a major obstacle for several therapeutic strategies. Tumor cells have adapted to this acidification by upregulation of several H(+)-extruding transporter systems and proteins to cope with this compromised situation. One of these proteins is carbonic anhydrase IX (CA IX), which catalyzes the reversible hydration of carbon dioxide to carbonic acid outside the cell, leading to an acidic extracellular pH and a physiological intracellular pH. The aim of this article was to study semiquantitatively the expression of CA IX in non-small cell lung cancer (NSCLC) and to assess the existence of a possible relationship between CA IX expression and tumor FDG uptake, reflecting glucose metabolism. The levels and the extent of CA IX expression were estimated in immunohistochemical stained, formalin-fixed, paraffin-embedded tissue samples from 18 patients with NSCLC and compared with FDG uptake in FDG-PET imaging. We found a statistically significant correlation between CA IX Hscores and SUVmax and SUVmean values of the primary tumor. This relationship provides indirect evidence for cotranscription of glucose transporters and hexokinases that drive tumor hyperglycolysis and for CA IX governed by hypoxia-inducible factor-1 and suggests that, in the future, it may be possible to identify NSCLC patients who are most likely to benefit from CA IX targeting therapy on the basis of FDG-PET imaging.

P-glycoprotein (P-gp) is a drug efflux transporter with broad substrate specificity localized in the blood-brain barrier and in several peripheral organs. In order to understand the role of P-gp in physiological and patho-physiological conditions, several carbon-11 labelled P-gp tracers have been developed and validated. This review provides an overview of the spectrum of radiopharmaceuticals that is available for this purpose. A short overview of the physiology of the blood-brain barrier in health and disease is also provided. Tracer kinetic modelling for quantitative analysis of P-gp function and expression is highlighted, and the advantages and disadvantages of the various tracers are discussed.

Tissue hypoxia results from an inadequate supply of oxygen (O2) that compromises biological functions. Structural and functional abnormalities of the tumour vasculature together with altered diffusion conditions inside the tumour seem to be the main causes of tumour hypoxia. Evidence from experimental and clinical studies points to a role for tumour hypoxia in tumour propagation, resistance to therapy and malignant progression. This has led to the development of assays for the detection of hypoxia in patients in order to predict outcome and identify patients with a worse prognosis and/or patients that would benefit from appropriate treatments. A variety of invasive and non-invasive approaches have been developed to measure tumour oxygenation including oxygen-sensitive electrodes and hypoxia marker techniques using various labels that can be detected by different methods such as positron emission tomography (PET), single photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), autoradiography and immunohistochemistry. This review aims to give a detailed overview of non-invasive molecular imaging modalities with radiolabelled PET and SPECT tracers that are available to measure tumour hypoxia.

Neuroendocrine tumors (NETs) are relatively rare tumors, mainly originating from the digestive system, able to produce bioactive amines and hormones. NETs tend to be slow growing and are often diagnosed when metastatic. The localization of a NETs and the assessment of the extent of disease are crucial for management. Commonly used diagnostic techniques include morphological imaging (ultrasound, computerized tomography, magnetic resonance), and functional imaging (somatostatin receptor scintigraphy, positron emission tomography techniques). Treatment is multidisciplinary and should be individualized according to the tumor type, burden, and symptoms. Therapeutic tools include surgery, interventional radiology, and medical treatments such as somatostatin analogues, interferon, chemotherapy, new targeted drugs and peptide receptor radionuclide therapy (PRRT) with radiolabeled somatostatin analogues. NETs usually over-express somatostatin receptors, thus enabling the therapeutic use of somatostatin analogues, one of the basic tools, able to reduce signs and symptoms of hormone hypersecretion, improve quality of life, and slow tumor growth. PRRT with somatostatin analogues 90Y-DOTATOC and 177Lu-DOTATATE has been explored in NETs for more than a decade. Present knowledge and clinical studies indicate that it is possible to deliver high-absorbed doses to tumors expressing sst2 receptors, with partial and complete objective responses in up to 30% of patients. Side effects, involving the kidney and the bone marrow, are mild if adequate renal protection is used. Moreover, a consistent survival benefit is reported. As NETs may also express cholecystokinin 2, bombesin, neuropeptide Y or vasoactive intestinal peptide receptors even simultaneously, the potential availability and biological stability of radio-analogues will improve the multireceptor targeting of NETs.

Radiolabelled peptides and monoclonal antibodies are an emerging class of radiopharmaceuticals for imaging inflammation with clinical implications for several chronic inflammatory disorders for diagnosis, therapy decision making and follow up. In the last decades, a number of novel monoclonal antibodies and peptides have been introduced for the treatment of different inflammatory disorders and also labelled with a variety of radionuclides depending upon the specific applications, diagnostic or therapeutic, by using direct or indirect methods. These radiopharmaceuticals bind to their targets with high affinity and specificity and therefore have an excellent diagnostic potential for the imaging of patients with chronic inflammatory diseases. In this review article we describe the characteristics of peptides, cytokines and monoclonal antibodies with a particular emphasis on their role in therapy decision making and follow up in different inflammatory diseases.

Prostate cancer is one of the most common causes of cancer in men. Evaluating the different stages of prostate cancer with conventional imaging techniques still proves difficult. Nuclear imaging might provide a technique that is able to evaluate prostate cancer, but clinical application has been limited due to lack of accuracy of current radiopharmaceuticals. The development of radiopharmaceuticals that can be targeted to specific antigens, overexpressed in prostate cancer, but sparse in normal tissue, is crucial. Peptides are of particular interest because of their favourable characteristics, leading to increased attention for nuclear imaging of the gastrin-releasing-peptide-receptor (GRPR) with radiolabelled bombesin-like peptides. Several derivatives of bombesin and its truncated form have been prepared for imaging with single photon emission computed tomography (SPECT) or positron emission tomography (PET), thereby delivering potent candidates for further clinical evaluation. This article provides an overview of the development and preclinical evaluation of radiolabelled bombesin analogues for in vivo targeting of GRPR in prostate cancer. The effect of the radionuclide, chelator, spacer and unnatural amino acids on affinity, metabolic stability and image quality are discussed, as well as agonistic or antagonistic properties. Potent candidates are proposed based on these selection criteria: (I) high affinity for GRPR, with rapid and specific tumour uptake (II) high hydrophilicity resulting in the preferred renal-urinary mode of excretion and low hepatobiliary excretion, (III) high stability, but relatively rapid clearance from blood. Also, a summary is made of clinical studies that report on the detection of prostate cancer with GRPR targeted radiopharmaceuticals.

This work reports the synthesis, radiolabelling and preliminary in vivo evaluation of [(123)I]-(4-fluorophenyl){1-[2-(4-iodophenyl)ethyl]piperidin-4-yl}methanone. The tributylstannylprecursor was synthesized with a yield of 30%. Radiolabelling was performed using an electrophilic iododestannylation. Tracer yield was 80%, radiochemical purity was >95% and specific activity was at least 55 Ci/micromol. Log P was 1.5. The tracer showed uptake in mice brain (2.72% ID/g tissue at 5 min p.i.) and therefore will be evaluated further by regional brain biodistribution and displacement studies in rabbits.

Background: Cervical spine manipulation is one of the many interventions practiced by health professionals to treat musculoskeletal disorders of the cervical spine. Although serious consequences of manipulation have been documented, the incidence is thought to be rare. More frequently, there may be minor transient side effects after manipulation of the cervical spine, such as headache, dizziness, and nausea. One of the hypothesis is that these side effects are caused by ischemia in the areas perfused by the vertebral arteries., Objective: The purpose of this study was to investigate whether manipulation of the cervical spine can influence blood flow in the brain., Methods: Single photon emission computed tomography was used to examine changes in regional cerebral blood flow caused by cervical spine manipulation (CSM) performed by a physiotherapist to 15 volunteers, using a 1-day split-dose Technetium 99m-ethyl cysteinate dimer single photon emission computed tomography activation paradigm., Results: One brain region was identified showing a decreased regional cerebral blood flow after manipulation. This region was situated in the anterior lobe of the left cerebellum (-42, -48, -24)., Conclusions: These findings suggest that cerebellar hypoperfusion may occur after CSM. This could explain why certain people experience headache, dizziness, or nausea after CSM. Further investigation into patient symptoms in the presence of cerebellar hypoperfusion and the possible link of these findings with other adverse reactions are warranted.

Background: Using conventional imaging methods, including magnetic resonance imaging and labeled leukocyte scanning, the diagnosis of infection in the postoperative spine remains a diagnostic challenge. Recently, promising results have been reported using 18F-fluorodeoxyglucose positron emission tomography for various infectious problems. This study aimed to investigate the value of 18F-fluorodeoxyglucose positron emission tomography in patients suspected of having spinal infection after previous surgery of the spine., Methods: Fifty-seven consecutive patients with a history of previous spinal surgery were prospectively included between February 1999 and June 2001. 18F-fluorodeoxyglucose positron emission tomography was performed 60 to 90 minutes after injection of 370 MBq 18F-fluorodeoxyglucose. Images were scored visually and semiquantitatively by two blinded, independent, certified nuclear medicine physicians, experienced with positron emission tomography. Differences were assessed by consensus. Results were correlated with final diagnosis allowing calculation of sensitivity, specificity and accuracy. Receiver operating characteristic analysis was performed to find optimal cut-off values., Results: Fifteen patients had spinal infection. Using the most sensitive cut-off values sensitivity, specificity and accuracy were 100%, 81%, and 86%, respectively, for both visual and semiquantitative scoring. In the group without metallic implants (n = 27), false positives (n = 2) only occurred in the first 6 months after surgery. In the group with metallic implants (n = 30), false positives (n = 6) were not confined to recently operated patients., Conclusions: Overall accuracy was excellent (86%) with a negative predictive value of 100%. 18F-fluorodeoxyglucose positron emission tomography holds promise to become the standard imaging technique in this difficult patient population, as it is straightforward, provides a rapid result (2 hours) and because accurate alternatives are lacking.

The pattern of the specific 5-HT2A (5-hydroxytryptamine 2A receptor) antagonist 123I-5-I-R91150 was measured in 10 healthy dogs without neurologic and behavior abnormalities. Eight cortical regions (left and right fronto-, temporo-, parieto-, and occipitocortical area), one global subcortical region (including the thalamic system) were compared with a reference region lacking receptors; that is, the cerebellum. The 123I labeled radioligand was injected intravenously 100-200 minutes before acquisition. Both transmission and emission data were obtained with a triple head gamma camera equipped with high-resolution fanbeam collimators. The emission data were corrected for scatter and attenuation. To delineate different cerebral regions more accurately, the regions of interest (ROI) defined in a former study on brain perfusion measured with 99mTc-ethyl cysteinate dimer (ECD) in the same dogs were used. The co-registration of the 99mTc-ECD and the 123I-5-I-R91150, obtained from each dog, was realized with the help of corresponding transmission maps. By normalizing each regional cerebral activity to the activity observed in the cerebellum, the regional radioactivity (binding index) could be relatively quantified. Highest brain uptake was noted in the frontocortical brain areas (right: 1.85, left: 1.89), followed by the temporocortical region (right: 1.58, left: 1.56). Least uptake was noted in the more caudal and middle brain regions [occipito- (right: 1.46, left: 1.41), parietocortical (right: 1.30, left: 1.26), and striatal region (1.19)]. No gender nor age influence was noted in this series. The 123I labeled serotonin-2A receptor ligand seems to have similar cortical binding in the normal canine brain, as shown in humans and other animal species. A frontocortical to occipitocortical (rostrocaudal) binding index gradient was identified within the dog, which has not been seen in imaging studies from humans and other animal species. The significance of these results will need further investigation. This normative data can be used to compare regional brain uptake of the 123I-radioligand to dogs with behavioral disorders related to the serotonergic system, in future studies.

In the presurgical evaluation of patients with partial epilepsies, the most extensively studied functional neuro-imaging modality to define the origin of seizure onset is fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET). Generally, this technique reveals a widespread zone of interictal glucose hypometabolism in the region of the epileptogenic focus. However, the technique may miss the epileptogenic region and FDG PET abnormalities may extend beyond the seizure onset zone. Consequently, for the precise identification of epileptogenic regions more specific imaging probes than FDG are warranted. This review considers the clinical utility of iomazenil (IMZ) SPET and flumazenil (FMZ) PET for the precise localization of epileptogenic foci in partial epilepsy syndromes.

In the past few decades, our understanding of the central nervous system has evolved from one of an immune-privileged site, to one where inflammation is pathognomonic for some of the most prevalent and tragic neurodegenerative diseases. Current research indicates that diseases as diverse as multiple sclerosis, stroke and Alzheimer's disease exhibit inflammatory processes that contribute to cellular dysfunction or loss. Inflammation, whether in the brain or periphery, is almost always a secondary response to a primary pathogen. In head trauma, for example, the blow to the head is the primary event. What typically concerns the neurologist and neurosurgeon more, however, is the secondary inflammatory response that will ensue and likely cause more neuron loss than the initial injury. This paper reviews the basic neuroinflammatory mechanisms, the potential neurotoxic mediators during activation of microglia, the brain resident macrophages, and their role in neurodegeneration. Alzheimer's disease is taken as a prototype for exploring these mechanisms, as it expresses more than 40 inflammatory mediators, it is the most extensively studied disorder in terms of immune-related pathogenesis, and because of its importance as the most prevalent type of dementia. Tools for the visualization of these neuroinflammatory processes, both structural and mainly functional, are critically reviewed and discussed.

There is increasing interest in mapping receptors in vivo by using functional imaging modalities such as single photon emission tomography (SPET) and positron emission tomography (PET). Since SPET is a more accessible functional imaging modality than PET and, overall, it is more economical, radioligands suitable for this technique are in greater demand. Recently, 123I-5-I-R91150, a radioligand with high selectivity and affinity for 5-HT(2A) receptors in the brain, was introduced for SPET. This study reports on the whole-body distribution and brain uptake of the selective 123I-5-I-R91150 ligand in four normal dogs. The frontal to cerebellar ratio of uptake in time was determined in three dogs. Time-activity curve of venous blood was determined in one dog. Maximal global brain uptake was found at 10-60 min post-injection. Higher brain uptake was noted in the frontal cortical areas compared to the cerebellum. The frontal-cerebellar ratio reached the highest values at 90-180 min. Reversibility and pharmacological selectivity of ligand binding was demonstrated through displacement and blocking studies with the 5-HT(2A) receptor antagonist ketanserin. This study demonstrates that the specific 5-HT(2A) iodinated ligand can be used for imaging and semi-quantification of the 5-HT(2A) receptors in the canine brain in vivo by using SPET., (Copyright 2002 Lippincott Williams & Wilkins)

The least invasive of all surgical weight-lowering procedures is the adjustable laparoscopic gastric banding (ALGB) technique. A rare complication (0.9%-1.8% of patients) but one that may require surgical revision is leakage of the gastric banding device. This paper reports on the usefulness of technetium-99m scintigraphy for the assessment of gastric band leaks as compared with radiography. Between March 1997 and October 2001, 23 obese patients (20 women and 3 men; mean age 35 years; range 23-60 years; mean body mass index before gastric banding procedure, 39.2 kg/m(2); range 29.3-52.1 kg/m(2)) were referred for exclusion of gastric banding leakage by means of radiography and (99m)Tc-pertechnetate scintigraphy. Both procedures were performed on the same day in all patients. Two patients underwent both procedures, respectively two and three times. A total of 27 radiographic and scintigraphic examinations were performed. Radiographs were judged positive for leakage when escape of contrast agent through a defect in the gastric banding device was visualised or when indirect criteria, e.g. smooth passage of barium suspension through the stoma after injection of contrast agent, were present. Scintigraphic images were judged positive when tracer disappearance out of the banding device and uptake in the thyroid gland as well as enhancement of the gastric mucosa were observed 30 min and/or 3 h post injection. Overall sensitivity, specificity and accuracy for radiography and (99m)Tc scintigraphy were 81.8% vs 81.8%, 75% vs 100% and 77.7% vs 92.6%. Leakage from the reservoir or the connecting tube is a late complication of ALGB. The presented data suggest that (99m)Tc-pertechnetate scintigraphy is more efficient than radiography in determining the presence of such leaks.

Unlabelled: The aim of this study was to determine the human biodistribution and radiation dosimetry of (99m)Tc-RP527, a promising radioligand for the visualization of gastrin-releasing peptide (GRP) receptor-expressing human malignancies., Methods: Whole-body scans were obtained up to 48 h after intravenous injection of 555 MBq (99m)Tc-RP527 in each of 6 subjects. Blood samples were taken at various times up to 48 h after injection. Urine was collected up to 48 h after injection for calculation of renal clearance and whole-body clearance. Time-activity curves were generated for the thyroid, heart, breasts in women, testes in men, and liver by fitting the organ-specific geometric mean counts, obtained from regions of interest, on the respective images as a function of the time after injection. The MIRD formulation was applied to calculate the absorbed radiation dose for various organs., Results: The serial whole-body images showed rapid hepatobiliary excretion, resulting in low background and potentially high-contrast imaging of the thoracic region. Imaging of abdominal tumors may prove problematic, however, because of the extensive bowel activity. (99m)Tc-RP527 was predominantly cleared by the kidneys and to a lesser extent by the gastrointestinal tract. The mean excretion in the urine (+/-SD) at 48 h after injection was 58.3 +/- 5.4 percentage of the injected activity corrected for decay to the time of injection. The highest absorbed doses were received by the excretory organs (i.e., the urinary bladder and gallbladder wall). The average effective dose of (99m)Tc-RP527 was estimated to be 0.0095 mSv/MBq., Conclusion: The biodistribution of (99m)Tc-RP527 revealed low lung, myocardial, and liver uptake, which allowed early imaging of the supradiaphragmatic region with a favorable dosimetry (including effective dose) for administered activities required for SPECT imaging.

Single photon emission computed tomography (SPECT) of the brain using perfusion tracers allows estimation of regional brain perfusion. This allows in vivo examination of brain function in the setting of neuropsychologic and pathophysiologic changes. However functional imaging data on brain perfusion in dogs are limited. Hence, the aim of this study was to determine the scintigraphic regional perfusion pattern of the normal canine brain. Ten healthy shepherd type dogs were injected with 925 MBq Technetium-99m ethyl cysteinate (ECD) 20 minutes before the examination. Acquisition was performed using a triple head gamma camera equipped with fanbeam collimators. Uniform attenuation correction and triple energy window correction were applied. Computed tomographic images were obtained from the same dogs, reoriented along the orbito-meatal axis and SPECT perfusion data were coregistered to the CT-volume data. Based on morphological and suggested brain divisions, regions-of-interest (ROIs) were defined for the bilateral frontocerebral, temporocerebral, parietocerebral, occipitocerebral, cerebellar, thalamic, and striatal area. Regional count density was normalized on total counts. All dogs had the highest uptake in the thalamic/striatal area compared to a rather homogeneous cerebral uptake. No significant left/right count differences were found, but a rostro-caudal gradient (+12-13%) was present. In this group, age and gender did not influence the perfusion pattern.

Reliable and high-resolution reference data for regional cerebral blood flow measured with single-photon emission tomography (SPET) are necessary for optimal clinical and research use. Therefore, a large dataset of normal technetium-99m labelled ethylene cysteine dimer (ECD) perfusion SPET in carefully screened healthy volunteers with an age range spanning six decades was created, with correction for non-uniform attenuation and scatter and based on an anatomically standardised analysis. Eighty-nine healthy volunteers, stratified for gender (46 females, 43 males; age 20-81 years), were included. Twelve volunteers underwent repeated 99mTc-ECD SPET after 2.5+/-2.3 weeks. An automated whole-brain volume of interest analysis with MANOVA as well as voxelwise analysis using SPM99 was conducted. Average intersubject variability was 4.8% while intrasubject reproducibility was 3.0%. An age-related decline in tracer uptake was found in the anterior cingulate gyrus, bilateral basal ganglia, left prefrontal, left lateral frontal and left superior temporal and insular cortex (all P=0.001-0.02). There was an overall increase in right/left asymmetry with age, which was most pronounced in the frontal and temporal neocortex. The most significant correlations between AI and age decade were found in the prefrontal (R=0.35, P=0.001) and superior temporal neocortex (R=0.43, P<0.001). Women had significantly higher uptake in the right parietal cortex (P<0.001), while men showed higher uptake in the cerebellum and the left anterior temporal and orbitofrontal cortex (all P<0.01). This normative dataset allows age- and gender-specific patient and group assessment of 99mTc-ECD perfusion SPET under a wide variety of clinical circumstances in relation to normal variations and highlights the importance of both age- and gender-specific normal datasets for optimal analysis sensitivity.

Radionuclide angiography with technetium-99m ethyl cysteinate dimer (ECD) allows non-invasive estimation of absolute cerebral blood flow (CBF), either by graphical Patlak-Gjedde analysis (PGA) or by spectral analysis (SA). Other methods estimate CBF by means of single-point arterial or venous sampling. The aim of this study was to evaluate radionuclide scanning and single-point venous sampling as potential clinical non- to minimally invasive methods for CBF determination in a large set of carefully screened healthy volunteers over the adult age range. Eighty-three carefully screened healthy volunteers (20-81 years, 43 males, 40 females) underwent planar radionuclide angiography with 925 MBq 99mTc-ECD. After correction for camera dead-time loss, hemispheric CBF was calculated from brain perfusion indices (BPI): BPI(G) for PGA and BPI(S) for SA. Of the volunteers, 49 also underwent venous sampling 6 min post injection, from which the lipophilic octanol extraction fraction and hemispheric brain fractionation index (BFI) were determined. All datasets were correlated and evaluated as a function of age and gender. Intrasubject variability for the BPI measurements was assessed in 11 volunteers by repeat study within 2 weeks of the first acquisition. Graphical and spectral analysis BPIs were strongly correlated (R=0.846, P<0.00001). This correlation coefficient increased to R=0.903 for the 74 cases in which graphical analysis was not hampered by temporal tracer retention in cervicobrachial venous valves. The BFI was weakly correlated to both BPI indices (BPI(G): R=0.34, P=0.02; BPI(S): R=0.31, P=0.04). The right hemisphere showed significant asymmetry for BPI(S) (AI=2.7%+/-4.3%, P<0.001), in correspondence with previous 99mTc-ECD data. BPI(G), BPI(S) and BFI were all inversely related to age, with an increased gradient after the age of 55 years, while there was no significant gender difference. The ratio of BPI(G) to BIP(S), which is a measure of the cerebral extraction fraction for 99mTc-ECD, was not dependent on age. Intersubject variability was 15.5% for both radionuclide scanning-based methods and 18.2% for venous sampling, and in all cases was independent of age. A much lower intrasubject variability was observed for BPI(S) (7.2%) than for BPI(G) (12.6%). This study provides reference values for normal perfusion indices assessed by graphical and spectral analysis. The results also indicate that spectral analysis allows the most reproducible estimate of hemispheric perfusion by means of an operator-independent and objective approach. Whereas accurate calibration of normal BPI(S) values to hemispheric CBF with established methods needs to be performed, non-invasive calculation of regional absolute CBF using 99mTc-ECD is possible by application of a linearisation algorithm.

This study reports on the biodistribution and dosimetry of technetium-99m ciprofloxacin, a radio-ligand developed for the visualisation of bacterial infection. Whole body scans were performed up to 24 h after intravenous injection of 370 MBq 99mTc-ciprofloxacin in three male and three female volunteers. Blood samples were taken at various times up to 24 h after injection. Urine was also collected up to 24 h after injection, allowing calculation of renal clearance and interpretation of whole body clearance. Time-activity curves were generated for the thyroid, heart, liver and whole body by fitting the organ-specific geometric mean counts, obtained from regions of interest. The MIRD formulation was applied to calculate the absorbed radiation doses for various organs. The images showed rapid, predominantly urinary excretion of 99mTc ciprofloxacin, with low to absent brain, lung and bone marrow uptake and low liver uptake and excretion. Accordingly, imaging conditions are excellent for both the thoracic and the abdominal region, even at early time points (60 min) post injection. In none of the volunteers was the gallbladder visualised. Approximately 60% of the injected activity was recovered in urine by 24 h post injection. The highest absorbed doses were received by the urinary bladder wall, the thyroid, the upper large intestine, the lower large intestine and the uterus. The estimated mean effective dose for the adult subject, taking into account the weight factors of the ICRP60 publication, was 0.0083 mSv/MBq. The amount of 99mTc ciprofloxacin required for adequate planar and tomographic imaging results in an acceptable effective dose to the patient.

Background: The noninvasive diagnosis of chronic musculoskeletal infections remains a challenge. Recent studies have indicated that fluorine-18 fluorodeoxyglucose-positron emission tomography is a highly accurate imaging technique and is significantly more accurate than the combination of a bone scan and a white blood-cell scan for the diagnosis of chronic infection in the central skeleton (p < 0.05). However, patients who had had surgery within the previous two years were excluded from study. It was our aim to evaluate the technique in an unselected, clinically representative population., Methods: Sixty patients with a suspected chronic musculoskeletal infection involving the central skeleton (thirty-three patients) or the peripheral skeleton (twenty-seven patients) were studied with fluorine-18 fluorodeoxyglucose-positron emission tomography. Thirty-five patients had had surgery within the previous two years. The fluorine-18 fluorodeoxyglucose-positron emission tomography studies were read in a blinded, independent manner by two experienced readers. The final diagnosis was based on histopathological studies or microbiological culture (eighteen patients) or on clinical findings after at least six months of follow-up (forty-two patients)., Results: On the final composite assessment, twenty-five patients had infection and thirty-five did not. All twenty-five infections were correctly identified by both readers. There were four false-positive findings; in two of these cases, surgery had been performed less than six months prior to the study. The sensitivity, specificity, and accuracy were 100%, 88%, and 93% for the whole group; 100%, 90%, and 94% for the subgroup of patients with a suspected infection of the central skeleton; and 100%, 86%, and 93% for the subgroup of patients with a suspected infection of the peripheral skeleton. Interobserver agreement was excellent (kappa = 0.97)., Conclusions: Fluorine-18 fluorodeoxyglucose-positron emission tomography is highly accurate as a single technique for the evaluation of chronic musculoskeletal infections. It is especially valuable in the evaluation of the central skeleton, where white blood-cell scans are less useful. Because of its simplicity and high degree of accuracy, it has the potential to become a standard technique for the diagnosis of chronic musculoskeletal infections. Further studies are needed to assess its ability to identify infections at the sites of total joint replacements and to distinguish infection from aseptic loosening of these prostheses.

A stereotactic, normal perfusion database is imperative for optimal clinical brain single-photon emission tomography (SPET). However, interdepartmental use of normal data necessitates accurate transferability of these data sets. The aim of this study was to investigate transfer of three normal perfusion databases obtained in the same large population of healthy volunteers who underwent sequential scanning using multihead gamma cameras with different resolution. Eighty-nine healthy adults (46 females, 43 males; aged 20-81 years) were thoroughly screened by history, biochemistry, physical and full neurological examination, neuropsychological testing and magnetic resonance imaging. After injection of 925 MBq technetium-99m labelled ethyl cysteinate dimer (ECD) under standard conditions, 101 scans were acquired from all subjects (12 repeat studies) on a triple-head Toshiba GCA-9300A (measured average FWHM 8.1 mm). Ninety-one sequential scans were performed on a dual-head Elscint Helix camera (FWHM 9.6 mm) and 22 subjects also underwent imaging on a triple-head Prism 3000 (FWHM 9.6 mm). Images were transferred to the same processing platform and reconstructed by filtered back-projection with the same Butterworth filter (order 8, cut-off 0.9 cycles/cm) and uniform Sorensen attenuation correction (mu = 0.09). After automated rigid intrasubject registration, all subjects were automatically reoriented to a stereotactic template by a nine-parameter affine transformation. The databases were analysed using 35 predefined volumes of interest (VOIs) with normalisation on total VOI counts. For comparison, the high-resolution data were smoothed with a 3D Gaussian kernel to achieve more similar spatial resolution. Hoffman phantom measurements were conducted on all cameras. Partial volume effects after smoothing varied between -6.5% and 10%, depending on VOI size. Between-camera reproducibility was 2.5% and 2.7% for the Toshiba camera versus the Helix and the Prism database, respectively. The highest reduction in between-camera variability was achieved by resolution adjustment in combination with linear washout correction and a Hoffman phantom-based correction. In conclusion, transfer of normal perfusion data between multihead gamma cameras can be accurately achieved, thereby enabling widespread interdepartmental use, which is likely to have a positive impact on the diagnostic capabilities of clinical brain perfusion SPET.

Purpose: Results of dedicated [(18)F]fluoro-2-deoxy-d-glucose (FDG) PET imaging in patients with suspected orthopedic infections are promising. This study evaluates the feasibility of dual-head gamma-camera coincidence (DHC) imaging in this population., Method: Twenty-four patients, referred for the confirmation or exclusion of orthopedic infection, were prospectively studied with consecutive FDG-dedicated PET and FDG DHC imaging. Images were read by two blinded readers experienced with FDG PET and compared with the final diagnosis, obtained by microbiologic proof in 11 patients and clinical follow-up of at least 9 months in 13 patients., Results: Nine patients had osseous infection on final diagnosis. Sensitivity, specificity, and accuracy in this limited series were (Reader 1/Reader 2), respectively, 100/100, 86/86, and 92/92% for FDG-dedicated PET and 89/89, 100/93, and 96/92% for FDG DHC imaging., Conclusion: Despite lower image quality for FDG DHC imaging, results in this limited series were comparable with the results of FDG-dedicated PET. Further studies are needed to confirm the utility of FDG DHC imaging in suspected chronic orthopedic infections in larger patient groups.

This phase I pilot study reports on (1) the safety and feasibility of 99Tc(m)-HL91, an amine oxime core radioligand that has shown oxygen dependent binding, and imaging; and (2) its usefulness for the visualization of local tumour recurrence of a biopsy proven squamous cell carcinoma of the head and neck (SCCHN) as compared to spiral computed tomogaphy (CT) and biopsy. Nine men (mean age 33 years, range 34-74 years) were prospectively included. For safety measurements, vital signs were recorded and serum chemical analysis carried out, with a complete blood cell count and urine analysis, and an ECG was performed prior to injection of 99Tc(m)-HL91 and repeated during the investigation. Single photon emission computed tomography (SPECT) scans of the head and neck, and of a standard, were performed at 2 h and 4 h post-injection of 740 MBq 99Tc(m)-HL91. Tumour-to-normal tissue background (T/N) ratios and percentage uptake were measured for all 99Tc(m)-HL91 scans. Spiral CT scans were obtained using a Somaton 4+ Siemens scanner within 1 week from the 99Tc(m)-HL91 scans. Based on CT and the 99Tc(m)-HL91 scan findings guided biopsies were performed. No adverse or subjective side effects were noticed. Vital signs, ECG findings, clinical laboratory, blood and urine assays remained stable in all patients. Spiral CT suggested local recurrence in 5/9 patients accompanied by nodal involvement in three, all of which proved positive on biopsy. 99Tc(m)-HL91 scintigraphy was false positive in one patient and true positive (TP) in 3/5 local recurrences and two out of three sites of lymph node involvement depicted by spiral CT. The mean T/N ratios at 2 h and 4 h in TPs were 1.28 (range 1.1-1.66) and 1.40 (range 1.0-1.6), respectively. The corresponding absolute percentages of 99Tc(m)-HL91 lesional uptake at 2 h and 4 h were mu = 0.05% (SD = 0.03%) and mu = 0.048% (SD = 0.035%). The findings suggest 99Tc(m)-HL91 is a safe radioligand and that metabolic binding in a large fraction but not all of local SCCHN recurrences may be expected. The inference that tumour 99Tc(m)-HL91 avidity could be a non-invasive measure of tumour hypoxia deserves however independent confirmation with needle oximetry.

This study investigated the feasibility of brain single photon emission computed tomography (SPECT) functional imaging in a neuropsychological test setting, following a single-day protocol with a split-dose paradigm. The Stroop Color Word Test (SCWT) is an example of a well-documented prefrontal activation task. In a split-dose protocol, ten right-handed healthy volunteers were injected twice with 370 MBq 99Tcm-ethyl cysteinate dimer while performing consecutively both series of card-reading of the SCWT. Images were reconstructed using filtered back-projection and normalized to a standard template in Talairach coordinates. Statistical Parametric Mapping (SPM96) was used to determine voxelwise significant changes. A first activation cluster was found in the left medial prefrontal cortex, consisting of the gyrus cinguli anterior and the gyrus frontalis medius and superior. A second activation cluster included the right gyrus frontalis dorsalis and medius. These findings confirm to a large extent the results of previous functional magnetic resonance imaging, positron emission tomography studies of Stroop-like tasks. The choice and validity of various methodological characteristics of the experimental design leading to these results is critically discussed. It is concluded that brain SPECT activation with the Stroop Color Word Test under standard neuropsychological conditions in healthy volunteers, is both technically and practically feasible.

Gastrin-releasing peptide (GRP) has been shown to be a tumour growth stimulating agent for a number of normal and human cancer cell lines. The tumour growth effect is a direct result of GRP binding to membrane G-protein coupled GRP receptors (GRP-R) on the cell surface. Available data on the role of GRP and GRP-R in human lung, prostate, breast, colorectal and gastric carcinoma are reviewed and it is suggested that radiolabelled agonists are preferable to antagonists for imaging and therapy as they appear to be internalised, yielding a higher target/background ratio. The use of rhenium or indium radiolabels for therapy may provide a new approach to GRP/bombesin expressing tumours.

This study aimed to investigate the feasibility of brain single-photon emission tomography (SPET) in the letter and category fluency paradigm of the Controlled Oral Word Association (COWA) test in healthy volunteers. Two groups each comprising ten right-handed healthy volunteers were injected twice with 370 MBq technetium-99m ethyl cysteinate dimer following a split-dose paradigm (resting and activation condition). Statistical parametric mapping (SPM96) was used to determine voxelwise significant changes. The letter fluency and the category fluency activation paradigm had a differential brain activation pattern. The posterior part of the left inferior prefrontal cortex (LIPC) was activated in both paradigms, with the category fluency task having an extra activation in the anterior LIPC. In the category fluency task, but not the letter fluency task, an activation in the right inferior prefrontal cortex was found. These findings confirm to a large extent the results of previous functional magnetic resonance imaging and positron emission tomography studies in semantic and phonological activation paradigms. The choice and validity of various methodological characteristics of the experimental design leading to these results are critically discussed. It is concluded that brain SPET activation with the letter fluency and category fluency paradigm under standard neuropsychological conditions in healthy volunteers is both technically and practically feasible.

High-frequency stimulation of the internal pallidum is an effective surgical approach for patients with advanced Parkinson's disease suffering from motor fluctuations and L-dopa induced dyskinesia. To study the acute effects of internal pallidum stimulation, changes in cerebral blood flow were measured by means of a single-day split-dose protocol using 99Tc(m)-ECD SPET. Nine patients with advanced Parkinson's disease and with a clinical picture predominated by tremor and drug-induced dyskinesia, were imaged before and immediately after electrostimulation. Brain perfusion data were mirrored to the same electrode side (five left and four right implants), co-registered and analysed statistically on a voxel-by-voxel basis (Statistical Parametric Mapping) and by an automated volume-of-interest approach. Acute stimulation of the internal pallidum induced a significantly decreased perfusion in the ipsilateral thalamus and striatum, as well as in the right parietal cortex. For the subgroup of seven patients with effective motor score improvements, a significant correlation between thalamic and striatal perfusion changes and UPDRS III motor score was present (P = 0.04). These results suggest that effective stimulation of the internal globus pallidus may produce symptom relief through decreased activity in pallido-thalamo-cortical circuits.

Donepezil is a highly potent and selective reversible achetylcholinesterase inhibitor. [(11)C]Donepezil is prepared by methylation with [(11)C]CH(3)I of the corresponding 6'-O-desmethylprecursor. Tissue distribution in mice revealed a high uptake in brain and rapid clearance from the blood. Metabolization studies in mice indicated the formation of one (11)C-labeled polar metabolite that didn't penetrate the blood-brain barrier. Regional brain distribution in rabbits didn't reflect the measured achetylcholinesterase distribution in rabbit brain.

Objective: To determine the effectiveness of technetium-99m labelled polyclonal human immunoglobulin G (HIG-scan) scintigraphy to detect spinal inflammation in patients with ankylosing spondylitis., Methods: Six ankylosing spondylitis (AS) patients with inflammatory axial pain and 3 spinal osteoarthritis (OA) patients with mechanical axial pain underwent an HMDP scan and an HIG-scan., Results: In both AS and spinal OA patients complaining of axial back pain, mechanical and inflammatory axial pain, bone scintigraphy revealed foci of markedly increased tracer accumulation. An HIG-scan of the region of increased uptake on bone scintigraphy did not reveal increased tracer accumulation in either group of patients., Conclusion: The data suggest that the HIG-scan is not useful in detecting inflammatory spinal lesions in ankylosing spondylitis.

We evaluated the methodological issues underlying the assessment of normal confidence intervals, as used in clinically based region-of-interest (ROI) semi-quantification of 99Tcm-HMPAO brain SPET. At two different centres equipped with high-resolution, triple-headed gamma cameras, HMPAO SPET scans were performed on two groups of 24 and 15 healthy volunteers respectively. Together with an operator-defined analysis (ODA), a semi-automated analysis (SAA) was conducted on the normal datasets in one centre. Tests of intra- and inter-observer variability were performed. Repeat scans were performed within 72 h after the first to analyse short-term regional inter-study variations. The overall regional uptake showed significant differences in most regions between both normal datasets. Intra-observer and inter-observer reproducibility were on average within 4% for the ODA, while for the SAA it was less than 1%. Inter-study variations were excellent for both centres, ranging from -4% to +3% for most regions studied. The variability in clinical brain perfusion studies largely depends on the reproducibility of the data analysis technique. A semi-automated approach shows clear advantages over an entirely operator-defined approach. Intra-subject repeat studies show enough stability for use as reliable baseline measurements in the construction of a normal database or to allow activation studies with high sensitivity.

This study reports on the distribution and radiation dosimetry of iodine-123 labelled trans-Z-iodomethyl-N,N-diethyltamoxifen (123-ITX), a promising radioligand for prediction of the therapeutic efficacy of unlabelled tamoxifen in human breast carcinoma. Whole-body scans were performed up to 24 h after intravenous injection of 123-ITX (mean: 146 MBq, range: 142-148 MBq) in five female volunteers, four with and one without thyroid blockade. Blood samples were taken at various times up to 24 h after injection. Urine was also collected up to 24 h after injection, allowing calculation of renal clearance and interpretation of whole-body clearance. Time-activity curves were generated for the thyroid, heart, brain, breasts, liver and gallbladder by fitting the organ-specific geometric mean counts, obtained from regions of interest. The MIRD formulation was applied to calculate the absorbed radiation doses for various organs. The images showed rapid hepatobiliary excretion, resulting in good imaging conditions for the thoracic region, whereas imaging of the abdominal region was impeded by extensive bowel activity. The breast to non-specific uptake ratio increased over time. 123-ITX was cleared by both the kidneys and the gastrointestinal tract. At 50 h p.i. the mean excretion in the urine was 89.4% (SD 5.7%). If the thyroid was not blocked, it was one of the critical organs. The highest absorbed doses were received by the excretory organs, i.e. the urinary bladder wall, the lower and upper large intestine, and the gallbladder wall. The average effective dose of 123-ITX was estimated to be 0.0084 mSv/MBq. The amount of 123-ITX required for adequate imaging of tumoral uptake results in an acceptable effective dose to the patient.

The aim of this study was to determine whether absolute 24 h DMSA uptake measurements (%DMSA) correlate well with 51Cr-EDTA clearance measurements in patients with severely reduced kidney function (SRKF). Between 1990 and 1997, 55 of 482 patients who underwent EDTA clearance measurements also underwent %DMSA within 1 week. Of these, 31 were women and 24 were men (mean age 60 years; range 19-77 years). EDTA clearance was determined using the slope-intercept method. Absolute depth- and background-corrected %DMSA were determined 24 h following the injection of 185 MBq per 1.73 m2 freshly prepared 99Tcm-DMSA. All patients had EDTA clearance < or = 60 ml.min-1. Eighteen patients (group A: 9 men and 9 women, mean age 55.8 years, range 28-73 years) had EDTA clearance > 20 ml.min-1 (mean +/- S.D. = 30.9 +/- 13.8 ml.min-1), whereas 37 patients (group B: 22 women and 15 men, mean age 62.0 years, range 19-77 years) had EDTA clearance < 20 ml.min-1 (mean +/- S.D. = 10.2 +/- 6.6 ml.min-1). EDTA clearance correlated well with %DMSA for the patients as a whole and for group A (r = 0.87, P = 0.73; r = 0.79, P = 0.0001 respectively). The regression equation suggests that %DMSA is not a marker of early renal dysfunction. In group B, the r-value (r = 0.48, P = 0.004) suggests that %DMSA is reliable as a marker of severe renal dysfunction to the extent that it provides rough information. In conclusion, %DMSA may not be used as a marker of early renal impairment. Additionally, in patients with severely reduced kidney function (EDTA clearance < 20 ml.min-1), it only provides a rough estimate.

Imaging with technetium-99m sestamibi offers a non-invasive approach to detect the presence of functional P-glycoprotein (Pgp), one of the major causes of multidrug resistance, in human malignancies. A clinical role for Pgp has been suggested in the subpopulation of primary neuroblastoma without amplification of the proto-oncogene MYCN. We wanted to evaluate the usefulness of 99mTc-sestamibi scintigraphy in the screening of neural crest tumours for the presence of Pgp. In ten children suffering from MYCN-negative neuroblastoma, ganglioneuroblastoma or ganglioneuroma, 99mTc-sestamibi imaging was performed at initial diagnosis. All patients underwent planar imaging 20-30 min and 3.5-4 h after intravenous injection of 740 MBq/1.73 m2 99mTc-sestamibi. Tumour to normal tissue ratios, as well as washout rates, were determined and compared with in vitro flow cytometric analysis of Pgp expression and function. Pgp expression was analysed flow cytometrically with the monoclonal antibodies 4E3 and MRK16, and Pgp function was evaluated by means of rhodamine 123 uptake and efflux either in the absence or in the presence of the Pgp inhibitor verapamil. In nine of ten patients, we found that the intratumoral 99mTc-sestamibi activity was comparable to the background activity, which might be suggestive of Pgp presence. This was confirmed flow cytometrically in all but one patient. 99mTc-sestamibi enhancement was seen in the primary tumour and the bone marrow metastases of one of the ten patients, and this result was concordant with a negative Pgp status. The findings presented suggest that 99mTc-sestamibi imaging results might correlate with the presence of functional Pgp in neural crest tumours without MYCN amplification.

The aim of this study was to determine if the qualitative 99Tcm-DTPA captopril radionuclide test (CRT) can help predict the acute detrimental effect of angiotensin-converting enzyme (ACE) inhibitors on renal function in hypertensive patients with solitary kidneys and chronic renal failure. Between 1991 and 1996, eight consecutive patients (6 males, 2 females) aged 27-73 years (mean 49.8 years) with known chronic renal failure and a solitary kidney referred for ACE treatment were included. 99Tcm-DTPA renography was performed at baseline and 1 h after the administration of 25 mg captopril within 1 week of each other. The CRT was performed in accordance with the criteria of the Working Party on the Diagnostic Criteria of Renovascular Hypertension with Captopril Renography. A beneficial or detrimental effect of subsequent ACE inhibitor treatment on renal function was determined by long-term follow-up (> or = 2 years). The CRT accurately predicted outcome in all eight patients subsequently treated with ACE inhibitors. In conclusion, our results suggest a role for qualitative 99Tcm-DTPA CRT in the prediction of renal function in patients with a solitary kidney and chronic renal failure subsequently treated with ACE inhibitors.

We report the in vivo evaluation (biodistribution, displacement and metabolization in blood, brain and heart) in mice and the metabolism in blood of human volunteers of iodine-123 labelled 1-(2-iodophenyl)-N-methyl-N-(1-methyl-propyl)-3-isoquinoline carboxamide ([123I]iodo-PK11195), a potential radioligand for visualization of inflammation in humans by single-photon emission tomography. In three series of 18 white mice (NMRI, 20-25 g), the concentration of radioactivity was measured during 48 h. Blood samples were taken, organs and intestines were excised, excretion was collected and all tissues were weighed and counted for radioactivity. The tissue uptake of radioactivity was measured as % of the injected activity/g of tissue. The excretion was expressed as % of the injected activity. Selective tissue uptake was investigated by pretreatment of another three series of 18 mice with cold PK11195 (1 mg/kg body weight). There was an inflow of [123I]iodo-PK11195 in the brain and among peripheral organs, heart (42.3%), lungs (133.5%) and kidneys (18.4%) had the highest uptake. After pretreatment with cold PK11195, there was a decrease in accumulation in the latter three organs, especially in heart (ca. 55%) and lungs (ca. 80%). Metabolite analysis was performed using high-performance liquid chromatography (HPLC). First, the extraction yield of [123I]iodo-PK11195 from blood and tissue was assessed, and found to be >90%. From blank blood samples and organs spiked with [123I]iodo-PK11195 it was concluded that no metabolization took place during the extraction procedure. Analysis of plasma, brain and heart of mice showed that 10 min p.i. [123I]iodo-PK11195 was the only significant (ca. 95%) radioactive compound in brain and heart where-as in plasma other radioactive products (>60%) appeared. Analysis of plasma samples of the three human volunteers at 7, 20, 37 and 50 min p.i. showed that [123I]iodo-PK11195 rapidly decomposes into two polar metabolites, which at these time points accounted for, respectively 31%, 62%, 75% and 77% of the total activity.

Unlabelled: Local malignant bone tumor excision followed by high-dose extracorporeal irradiation (300 Gy) and subsequent reimplantation is a unique technique for treatment of primary bone and cartilage tumors. The long-term scintigraphic findings of irradiated bone autografts in relation to clinical patient data were reviewed retrospectively., Methods: Thirty-seven patients (12 women, 25 men; age range 13.0-66.7 yr; average age 29.1 yr) were studied. Postsurgical anatomopathological diagnoses included osteosarcoma, 20 patients; chondrosarcoma, 7 patients; and other less-frequent primary osteogenic tumors, 10 patients. Three hundred ninety 99mTc-methylene diphosphonate (MDP) whole-body scans performed between 3 mo and 18.3 yr (mean 6.5 yr) after treatment were reviewed., Results: The 10-yr actuarial survival rate was 78%. After a mean period of 19.4 mo, 6 patients developed a local recurrence, and MDP scintigraphy detected the recurrence in 4. Distant metastases developed in 11 patients (30%), of which 10 were nonosseous. Initially, all autografts appeared as photon-deficient areas. Diffusely increased bone uptake was present at osteotomy sites and at articulating surfaces contiguous with autografts within the first few months after surgery. Of all 25 patients with adequate follow-up, 7 showed persistent decreased uptake up to 129 mo after surgery. The other patients developed partial tracer uptake after 19.6 mo, on average. In 6 patients, scintigraphic images consistent with complete revascularisation were noted later (mean 31.5 mo). Local, sometimes multiple, complications were noted in 22 patients, mainly mechanical graft-related (15) or infections (11). Scintigraphic sensitivity for mechanical complications was 100%. Significantly more fractures and collapses were seen when partial tracer uptake suggestive of revascularisation occurred. Altered bone stress gave rise to focal and diffuse scintigraphic abnormalities, often in the spine and lower extremities. In recent literature, similar clinical complication patterns are found for massive allografts., Conclusion: Skeletal scintigraphy is a sensitive technique for evaluating long-term follow-up of massive grafts to treat primary malignant bone tumors. Revascularisation and partial bone ingrowth are not sufficient conditions for a lower complication rate.

We performed a prospective study to establish the optimal background correction algorithm for the determination of differential renal function (DRF), using 99Tc(m)-diethylenetriamine pentaacetate (99Tc(m)-DTPA) in the presence of unilateral hydronephrosis, with 24 h 99Tc(m)-dimercaptosuccinic acid (99Tc(m)-DMSA) uptake as the 'gold standard'. From September 1996 to June 1997, 12 males and 4 females (mean age 10 years, range 1 month to 72 years), presenting with unilateral hydronephrosis, were studied. All patients underwent both DTPA renography and quantitative DMSA scintigraphy within 24 h. In all patients, using a surface method, the DRF of the obstructed kidney was determined using infrarenal, suprarenal and perirenal background correction, time intervals of 60-180 s (t1), 120-180 s (t2) and 80-140 s (t3), and the application or non-application of a Rutland-Patlak correction (RPC). In the absence of RPC, for all three types of background correction, no difference in DTPA DRF for any of the three time intervals was noted; higher DTPA DRF values were found (mean +/- S.D.: overestimates of 7.8+/-24.4%, 6.5+/-9.5% and 3.3+/-14.9% for suprarenal, infrarenal and perirenal background correction, respectively). Application of RPC resulted in an overall decrease in both the mean and standard deviation values, which was most pronounced with infrarenal background correction: -0.38+/-6.5% for t1, 0.31+/-6.3% for t2 and -1.3 +/-6.9% for t3 (t1 vs t2, P = 0.06; t3 vs t1 or t2, P = 0.04). Our results suggest that infrarenal background correction using t1 or t2 and RPC is the best algorithm for DRF estimation using 99Tc(m)-DTPA renography.

Unlabelled: Previous studies have shown the usefulness of divalent cobalt isotopes to visualize cerebral damage after stroke. The site of accumulation of cobalt ion is unknown but may be explained by neuronal influx, analogous to that of calcium ion. Additionally, uptake may be due to infiltrating leukocytes or protein-bound cobalt. The aims of this study were to compare 57Co-SPECT with leukocyte SPECT and to compare the SPECT findings with clinical outcome as scored by the Orgogozo scale., Materials: Ten patients with a CT scan positive for middle cerebral artery infarcts were included in the study (7 men, 3 women; mean age 70 yr). Technetium-99m leukocyte and cobalt-SPECT (interval 2-4 days) were made with a double-headed gamma camera, after the injection of 10-15 mCi 99mTc-HMPAO-labeled leukocytes and 0.4 mCi 57Co, respectively. Scans were performed within 5-30 days after onset of the first symptoms. Regions of interest (ROI) containing the area of infarction in the slices displaying enhanced radioactivity or the middle cerebral artery (MCA) region in four successive slices were defined for calculating enhancement ratios. The 99mTc leukocyte enhancement ratio (LER) and cobalt enhancement ratio (CER) were defined as the quotient of radioactivity in the ROI and an identical contralateral ROI. The MCA stroke-scale according to Orgogozo was used to assess neurological deficits at the time of scanning and discharge., Results: Cobalt-57 and 99mTc-HMPAO showed uptake in the infarcted brain area in five patients; the quantitative uptake in the infarcted brain area of the two tracers correlated significantly (p < 0.05). Both the LER and the CER correlated significantly (p < 0.05) with the Orgogozo score at the time of scanning. Only the LER correlated significantly (p < 0.05) with the Orgogozo score at discharge., Conclusion: Uptake of cobalt and leukocytes in the peri-infarct tissue suggests that 57Co may visualize a component of the inflammatory response. Divalent 57Co may be convenient to predict clinical prognosis after stroke.

Neuroblastoma (NB) tumour cells have a remarkable tendency to differentiate spontaneously or under the influence of certain drugs. It is not clear whether metaiodobenzylguanidine (MIBG) uptake correlates with differentiation of NB cells. In 28 tumours of 26 patients, iodine-123 MIBG uptake in primary NBs was studied in relation to tumour differentiation, tumour size, cell density and degree of necrosis in subsequently resected specimens. Genetic features such as the presence of chromosomal aberrations (1p-deletion and MYCN amplification) and/or P-glycoprotein (mdr-1 gene product) were also evaluated in relation to MIBG uptake. A highly variable and unpredictable intensity of MIBG uptake was observed in primary as well as secondary resected tumours. This intensity did not relate to any of the above-mentioned factors except that there was a trend towards more intense uptake with increasing size of the tumour. We conclude from our observations that, in contrast to commonly held opinion, well-differentiated tumours do not a priori show a lower MIBG uptake in vivo, even when there are a low number of viable cells and a high degree of necrosis. The degree of differentiation or tumour viability and necrosis following longstanding chemotherapeutic treatment cannot be predicted by the MIBG scan findings. The observed MIBG uptake may be importantly influenced by factors other than those associated with cellular differentiation.

We performed a retrospective study to determine the age- and sex-related normal values of absolute 99Tcm-DMSA uptake at 24 h in children with normal kidneys. Of the 576 scintigrams performed between 1993 and 1996, 136 (272 kidneys) were classified as 'normal' by two independent observers on the basis of the presence of a smooth cortical outline, the absence of cortical loss, relative uptake in the range 45-55% and normal echographic parenchymal findings. The 136 scintigrams were divided into eight groups based on the children's age: Group I, < 1 month (2 boys); Group II, 1-3 months (6 boys, 8 girls); Group III, 4-7 months (7 boys, 6 girls); Group IV, 8-12 months (8 boys, 8 girls); Group V, 13-24 months (14 boys, 4 girls); Group VI, 25-36 months (6 boys, 13 girls); Group VII, 37-120 months (13 boys, 19 girls); Group VIII, 121-180 months (8 boys, 10 girls). In contrast to the results of Morris et al. using absolute 99Tcm-DMSA uptake at 4-6 h, we found that combined left and right kidney uptake increased until age 8 months (Group I, 22.0 +/- 6.7%; Group II, 45.9 +/- 5.0%; Group III, 50.8 +/- 5.0%; Group IV, 56.9 +/- 8.5%; P = 0.019), after which it reached a plateau (Group V, 55.4 +/- 7.3%; Group VI, 60.1 +/- 7.8%; Group VII, 62.0 +/- 5.0%; Group VIII, 62.4 +/- 6.3%). Uptake at 24 h tended to be lower in the girls than in the boys, but this difference was not significant.