Positron Emission Transaxial Tomography Research Articles

Tumeurs germinales séminomateuses du testicule : diagnostic et traitement

Among germ cell tumours, seminomas hold a particular status related to their radio-sensitivity. Although radiotherapy remains the best treatment for Localized tumours of stage 1, in some cases, surveillance or chemotherapy may presently be considered as alternative therapies. Due to Long-term radiotherapy-related adverse effects, in particular the risk of second non-germ malignancies or cardiac morbidity, both dose and irradiation field are reduced in case of lymphatic retroperitoneal extension. Chemotherapy is the preferential treatment in more advanced stages, either with retroperitoneal bulky disease or with metastatic extension. Its efficacy allows Limiting surgical indications on residual masses, relying partly on the follow-up data of positron emission transaxial tomography assessment.

Blood Flow Imaging of the Brain: 50 Years Experience

Blood Flow Imaging of the Brain: 50 Years Experience

Tumeurs germinales séminomateuses du testicule : diagnostic et traitement

Among germ cell tumours, seminomas hold a particular status related to their radio-sensitivity. Although radiotherapy remains the best treatment for localized tumours of stage I, in some cases, surveillance or chemotherapy may presently be considered as alternative therapies. Due to long-term radiotherapy-related adverse effects, in particular the risk of second non-germ malignancies or cardiac morbidity, both dose and irradiation field are reduced in case of lymphatic retroperitoneal extension. Chemotherapy is the preferential treatment in more advanced stages, either with retroperitoneal bulky disease or with metastatic extension. Its efficacy allows limiting surgical indications on residual masses, relying partly on the follow-up data of positron emission transaxial tomography assessment.

Back pain and renal failure

A 40-year-old plumber was admitted to the emergency room of our hospital in October, 2003, with bilateral backache for 1 week. He had no other complaints. He had no previous medical history and was not on any treatment. On examination, his temperature (36 ·5°C), heart rate (80 beats per min), and blood pressure (140/70 mm Hg) were normal. There was no rash and no lympha-denopathy. Lungs were clear and heart sounds were normal. There was no oedema and he was passing urine normally. Abdomen was unremarkable except for tenderness of both costovertebral angles. Laboratory tests showed normal blood-cell counts but a severe renal failure: serum creatinine 390 µmol/L (normal: 35-106), with raised uric acid (2268 µmol/L: 200-500). Urinalysis showed microscopic haematuria and moderate proteinuria (600 mg/L). Neither crystals nor amorphous material was detected in the urinary sediment. Abdominal ultrasound showed enlarged kidneys (14 cm in length). A renal biopsy was done and haemodialysis started. The biopsy specimen showed a massive interstitial tumour infiltrate (figure, A) composed of a monomorphous population of small to medium-sized cells with round to oval nuclei, very fine chromatin, and scanty cytoplasm (figure, B). The widened interstitium compressed the tubular luminae but neither urate crystals nor tubular necrosis were seen; there were some mitotic figures. Immunohistochemical studies identified these cells as precursor T lymphoblasts because they were positive for several T-cell antigens, including CD2, CD3, and CD5, as well as for terminal deoxynucleotidyltransferase (TdT) (figure, C and D). The diagnosis of precursor T-lymphoblastic lymphoma was then made. Cytological examination of a bone-marrow aspirate showed massive lymphoblastic involvement, indicative of acute lymphoblastic leukaemia. A positron emission transaxial tomography (PET) scan showed increased metabolic activity in all bone-marrow areas, liver, spleen, and kidneys (figure, E). High doses of corticosteroids (intravenous methylprednisolone, 80 mg twice a day for 1 week) led up to a rapid return to normal of renal function. Tumour lysis secondary to corticosteroids could have been responsible for worsening of hyperuricaemia. Rasburicase (0·2 mg/kg/day for 1 week) was given. Once the final diagnosis was established, standard chemotherapy was started. As of October, 2004, he is on maintenance treatment, feels well, is in complete remission, and his serum creatinine is normal. Severe acute renal failure is a rare presentation of malignant haemopathies. There are two pathophysiological mechanisms. Hyperuricaemia due to increased nucleic-acid catabolism is the most frequent. Uric-acid nephropathy is characterised by tubular necrosis due to uric-acid crystallisation in the tubular lumen. In this setting, urate crystals are easily detectable by light microscopy, the size of the kidneys is within normal range, and patients are usually oliguric.

Imaging of hypoxia in human tumors with [F-18]fluoromisonidazole

Fluoromisonidazole (FMISO) has been shown to bind selectively to hypoxic cells in vitro and in vivo at radiobiologically significant oxygen levels. When labeled with the positron emitter fluorine-18 (F-18), its uptake in tissue can be detected quantitatively with high precision by positron emission transaxial tomography (PETT). This paper presents the first experiences with PETT imaging of [F-18]FMISO uptake in human malignancies, and describes the development of this technique as a tool for the non-invasive assessment of tumor hypoxia. Eight patients with selected cancers were imaged prior to primary radiotherapy, and 3 returned for follow-up scans, for a total of 11 imaging studies. Six of eight pre-radiotherapy studies revealed retention of [F-18FMISO in tumors that significantly exceeded plasma concentrations by 2 hr after drug injection; all five patients with head and neck primaries had such “positive” scans. An analytic method for the interpretation of [F-18] FMISO PETT images is presented, defining hypoxic elements within a tumor volume as regions with a threshold regional tumor:plasma [F-18]FMISO ratio of ?1.4 by 2 or more hours after injection. Toward the end of a course of fractionated radiotherapy, three repeat studies in patients with initially positive scans showed no tumor accumulation of drug above the threshold ratio of 1.4, suggesting reoxygenation had occurred. Pharmacokinetic and dosimetry data support continued use of [F-18]FMISO as a safe hypoxia probe. Two imaging protocols have been developed for human studies; a long protocol allows for more complete biodistribution and dosimetry information, and a shorter protocol facilitates increased patient accrual by applying a simple, clinically expedient imaging procedure. When correlated with tumor outcome, [F-18]FMISO PETT imaging may be developed as a predictor of tumor response to conventional radiotherapy. The implications of this technique in addressing persistent questions of tumor hypoxia in human oncology is discussed.

Technological advances in the study of reading: An introduction

Abstract Recent years have witnessed the development of several new computer‐driven technologies whose capabilities shed light on brain‐related issues germane to the field of reading. This paper describes the purpose and functional operation of these technologies, outlines their current contribution to our knowledge base, and provides some speculation regarding the role existing and emerging technologies will play in future diagnostic and Instructional reading endeavors. Included among the technologies are computerized axial tomography (CAT), Positron Emission Transaxial Tomography (PETT) .regional cerebral blood flow (rCBF) monitoring, Magnetic Resonance Imaging (MRI), and Brain Electrical Activity Mapping (BEAM).

An examination of the opiate receptor subtypes labeled by [ 3H]cyclofoxy: An opiate antagonist suitable for positron emission tomography

17- Cydopropylmethyl -3,14- dihydroxy -4,5- alpha-epoxy-6-beta -fluoromorphinan(cycloFOXY) is a fluorinated derivative of naltrexone suitable for labeling opiate receptors using positron emission transaxial tomography. Using the quantitative ligand binding method “binding surface analysis,” in vitro autoradiography, and site-directed alkylating agents, [ 3H]cycloFOXY is shown to label mu and kappa opiate binding sites in vitro. Similar results were obtained using [ 3H]naloxone. Additional experiments demonstrate that [ 3H]cycloFOXY administered in vivo also labels mu and kappa binding sites. The relevance of these findings are discussed from clinical and basic science perspectives.

Chronic morphine upregulates a μ-opiate binding site labeled by [ 3H]cycloFOXY: a novel opiate antagonist suitable for positron emission tomography

CycloFOXY (17-cyclopropylmethyl-3,14-dihydroxy-4,5-α-epoxy-6-β-fluoromorphinan) is a novel opiate antagonist synthesized as a ligand suitable for in vivo visualization of opiate receptors using positron emission transaxial tomography. In this paper we report that [ 3H]cycloFOXY labels two distinct opiate binding sites in rat brain membranes, tentatively identified as μ and κ. Furthermore, chronic administration of morphine results in a selective up-regulation of the μ binding site. The implications of this finding for models of the opioid receptors and the mechanism of the sodium effect are discussed.

The effect of ring-fluorination on the rate of O-methylation of dihydroxyphenylalanine (DOPA) by catechol-O-methyltransferase: Significance in the development of 18F-pett scanning agents

The three ring-fluorinated analogs of dihydroxyphenylalanine (DOPA) were synthesized and the kinetics of their O-methylation catalyzed by catechol-O-methyltransferase compared to those of DOPA. The affinities (Km) of 2-FDOPA, 5-FDOPA, DOPA, and 6-FDOPA were 20, 23, 55, and 552 μM, respectively, whilst the V max values were 4.0, 4.4, 5.0 and 5.4 nmol per min per mg protein. The importance of the low affinity and decreased rate constant of 6-FDOPA for COMT are discussed with regard to the use of 6-FDOPA as an 18-fluorine labeled probe for positron emission transaxial tomography (PETT).

Formula omitted]: The radioligand of choice for pett studies of the dopamine receptor in human brain

N-methylspiroperidol, the amide N-methyl analogue of the neuroleptic spiroperidol, was radiolabeled with fluorine-18, and its distribution in the baboon brain was studied using positron emission transaxial tomography. Stereospecific binding was demonstrated in the striatum (but not in the cerebellum) by pretreatment with (-)- or (+)-butaclamol. The kinetic distribution was similar to that of [ 18F]spiroperidol, but the absolute striatal uptake (in percent of administered dose) was at least two-fold higher. Analysis of baboon blood at 10 min after injection indicated that less than half of the radioactivity in the plasma was due to unchanged radioligand. Analysis of the metabolic stability of [ 18 F]-N- methylspiroperidol in rat brain for 4 hr indicated that, like [ 18F]spiroperidol, it is very stable to metabolic transformation in the rat central nervous system. Striatal uptake and retention in the rat was five-fold higher for [ 18 F]-N- methylspiroperidol than for [ 18F]spiroperidol. These results suggest that [ 18 F]-N- methylspiroperidol is an ideal choice for studies of the dopamine receptor in humans.

Comparison of three 18F-labeled butyrophenone neuroleptic drugs in the baboon using positron emission tomography.

The butyrophenone neuroleptics spiroperidol, benperidol, and haloperidol were radiolabeled with fluorine-18 and studied in baboon brain using positron emission transaxial tomography (PETT). Pretreatment of the baboon with a high pharmacological dose of (+)-butaclamol reduced the specifically bound component of radioactivity distribution in the striatum to approximately the radioactivity distribution found in the cerebellum. Comparative studies of brain distribution kinetics over a 4-h period indicated that either [18F]spiroperidol or [18F]benperidol may be suitable for specific labeling of neuroleptic receptors. In an 8-h study with [18F]spiroperidol, striatal radioactivity did not decline, suggesting that spiroperidol either has a very slow dissociation rate or that it binds irreversibly to these receptors in vivo. [18F]Haloperidol may not be suitable for in vivo PETT studies, because of a relatively high component of nonspecific distribution and a faster dissociation from the receptor. Analysis of 18F in plasma after injection of [18F]spiroperidol indicated rapid metabolism to polar and acidic metabolites, with only 40% of the total radioactivity being present as unchanged drug after 30 min. Analysis of the metabolic stability of the radioactively labeled compound in rat striatum indicated that greater than 95% of [18F]spiroperidol remains unchanged after 4 h.

Human primary visual cortex topography imaged via positron tomography

The visuotopic structure of primary visual cortex was studied in a group of 7 human volunteers using positron emission transaxial tomography (PETT) and 18F-labeled 2-deoxy-2-fluoro- d-glucose ([ 18F]DG). A computer animation was constructed with a spatial structure which was matched to estimates of human cortical magnification factor and to striate cortex stimulus preferences. A lateralized cortical ‘checker-board’ pattern of [ 18F]DG was stimulated in primary visual cortex by having subjects view this computer animation following i.v. injection of [ 18F]DG. The spatial structure of the stimulus was designed to produce an easily recognizable ‘signature’ in a series of 9 serial PETT scans obtained from each of a group of 7 volunteers. The predicted lateralized topographic ‘signature’ was observed in 6 of 7 subjects. Applications of this method for further PETT studies of human visual cortex are discussed.

Synthesis and pharmacological characterization of (+/-)-5,9 alpha-dimethyl-2-[2-(4-fluorophenyl)ethyl]-2'-hydroxy-6,7-benzomorphan (fluorophen), a ligand suitable for visualization of opiate receptors in vivo.

A fluorinated derivative of the benzomorphan opiate agonist phenazocine, (+/-)-5,9 alpha-dimethyl-2-[2-(4-fluorophenyl)ethyl]-2'-hydroxy-6, 7-benzomorphan (fluorophen), was prepared by N-acylation of (+/-)-5,9 alpha-dimethyl-2'-hydroxybenzomorphan with (p-fluorophenyl)acetyl chloride, followed by diborane reduction of the resulting amide. Fluorination produces only a twofold opiate receptor affinity loss when measured either by bioassay or receptor binding (selectivity mu congruent to delta greater than kappa). Labeled with 18F, fluorophen should be sufficiently potent to be useful as an in vivo probe for visualizing opiate receptors by positron emission transaxial tomography (PETT).

Fluorine-18 chemistry and its application to positron emission tomography

The decay properties of fluorine-18, t 1 2 = 110 min, 97% β + emission, ε max = 0.65 MeV, make it a near ideal tracer for use in positron emission transaxial tomography (PETT). The application of fluorine-18 has mainly been as a tracer in biologically active compounds in biomedical research. These include compounds where its position in the molecule is chosen to be biologically inactive, where its position is chosen to block a specific biochemical pathway or where it replaces fluorine-19 in the compound of interest. The synthetic challenges presented by working with no carrier added (NCA) or “carrier free” (CF) fluorine-18 have both similarities and differences from work with “normal” fluorination reactions. The broad scope of organofluorine chemistry is limited when dealing with fluorine-18 synthesis. The major factors to consider are the time scale of the synthesis, normally taking no longer than one to four hours for any single or multiple step procedure, the precursors available, they must have high specific activity and be readily preparable e.g. 18FF 2, anhydrous H 18F, aqueous 18F −, and the synthetic procedures which must result in yields adequate to the needs of the biomedical research. The lecture will cover the most useful preparative methods for the radionuclide and simple precursors, the precursor field in general, synthetic strategies utilizing the electrophilic or nucleophilic character of the labeled reagent, some specific examples such as the metabolic agent 2-deoxy-2-[ 18F]-fluoro-D-glucose, neuroreceptor ligand agents such as 18F-spiroperidol (spiperone) and others, 18F-labeled nucleosides, steroids, fatty acids and other compounds. Some examples of applications in biomedical research will be given and present and future challenges in research with this nuclide will be addressed in the context of its chemical and radiochemical properties.

Specific binding of [11C]spiroperidol in rat brain in vivo.

Spiroperidol labeled with carbon-11, a short-lived positron-emitting radionuclide, was used to determine the time course of specific binding of this radioligand to the neuroleptic receptor in vivo in the rat. The three major bran pools--specifically bound, nonspecifically bound, and free (unbound)--were determined over a 60-mm time course by a rapid filtration technique, utilizing (-)- and (+)-butaclamol pretreatments to assess total and nonspecifically bound activities, respectively, in striatum and cerebellum. The ratio of specifically to nonspecifically bound pools in the striatum was 4.1 at 30 min and 5.1 at 60 min. Thus [11C]spiroperidol may be useful for labeling neuroleptic receptors in vivo for serial studies using positron emission transaxial tomography.

PETT scanners probe 'frontiers' of brain

Sometime this summer, Robert Beck will place his head inside one of the nation's newest positron emission transaxial tomography (PETT) scanners. It will be a first for this particular device—in terms of scanning a human—but not for Beck, director of the University of Chicago's Franklin McLean Memorial Research Institute (FMI). He volunteered his head once before and is unlikely ever to forget the result. Visiting St Louis in the fall of 1980, when PETT studies with monkeys had been completed at Washington University, Beck volunteered to be the first human to be scanned with the university's prototype PETT VI. The resulting images (Figure) produced a surprise: an asymmetric distribution of blood in the left temporal lobe of Beck's brain. suspected I had a brain tumor, Beck recalls. Back at the University of Chicago's Pritzker School of Medicine, Beck discussed the scans with Jerre Levy, PhD, whose work includes extensive

Study of cerebral function with positron computed tomography.

Abbreviations: ACD, Annihilation coincidence detection; BGO, bismuth germanate; CBF, cerebral blood flow; CBV, cerebral blood volume; CMG, 3-(11C)-methyl-D-glucose; CMRGlc, cerebral metabolic rate for glucose; CMR02, cerebral metabolic rate for oxygen; CsF, cesium fluoride; CT, computed tomography; DG, deoxyglucose; FDG, 2-fluoro-2-deoxy-d-glucose; LC, lumped constant; OEF, oxygen extraction fraction; PCT, positron computed tomography; PETT, positron emission transaxial tomography; PT, physiological tomography.

Cyclotron isotopes and radiopharmaceuticals—XXIX. [formula omitted] for positron emission tomography

Cationic 81, 82 m Rb was produced via ( p, xn) reactions with E p = 32 → 16 MeV on Kr in >99.95% radionuclidic purity at a EOB + 3 h combined production rate of 17.3 mCi/μAh. The 81, 82 m Rb was evaluated in dogs as a myocardial perfusion agent in combination with quantitative positron emission transaxial tomography, and with a planar positron camera for focal plane tomography. The 81, 82 m Rb radionuclides are promising substitutes for 38K + at institutions which do not have an on-site accelerator.

External assessment of myocardial metabolism with [11C]palmitate in rabbit hearts.

To determine whether the rate of fatty acid utilization, reflecting myocardial oxygen consumption under steady-state conditions, can be assessed noninvasively, we assayed positron emission from [11C]palmitate (100 muCi) in isolated rabbit hearts and after intra-atrial injection in vivo. In 11 isolated hearts, clearance of 11C-radioactivity during a monoexponential portion of residue detection curves correlated with tension-time index (TTI)(r = 0.86) and peak dP/dt (r = 0.89). Among 9 hearts prelabeled with [14C]palmitate, 14CO2 production from neutral lipid stores correlated with TTI (r = 0.83). In vivo the decline of 11C-radioactivity was 1st order and constant when physiological conditions were maintained constant (slope of the semilog plot = 0.099 +/- 0.002 (SE) in counts/min) (n = 2 animals, 7 injections). Decline of activity changed predictably when oxygen requirements were increased by administration of methoxamine. Thus, residue detection of [11C]palmitate 1) permits external assessment of global myocardial metabolism in vitro, and 2) reflects effects of interventions that alter the rate of substrate utilization in vivo, and should, therefore, permit comparison of rates of regional myocardial metabolism in patients with detection of radioactivity by positron-emission transaxial tomography.

An improved isolated heart preparation for external assessment of myocardial metabolism

To facilitate characterization of myocardial metabolism with the use of positron-emitting tracers, we developed an isolated heart preparation designed to simulate physiological levels of flow and substrate extraction. Isovolumically beating hearts were perfused retrograde at 60 mmHg with modified non-recirculating Krebs-Henseleit (KH) solution with or without washed sheep red blood cells at a hematocrit of 25 or 40 (KH-RBC25, KH-RBC40). Left ventricular (LV) systolic pressure averaged 63 mmHg with KH alone, 78 with KH-RBC25, and 98 with KH-RBC40. LV dP/dt, pressure-time index, and oxygen consumption increased in an analogous fashion. Fatty acid extraction increased from 1.5% with KH to 11.8% in hearts perfused with KH-RBC40, although net uptake was not increased markedly because of the associated differences in flow (4.6 ml.g-1.min-1 with KH and 1.5 with KH-RBC40). Hearts perfused with erythrocyte-rich media exhibited functional and metabolic stability and less edema. The preparation avoids intrinsic limitations encountered with buffer-perfused hearts and should prove useful for characterization of cardiac metabolism with radiolabeled tracers relevant to positron emission transaxial tomography.