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Biomedical subjects

H N Wagner

Publications and source records attributed to H N Wagner.

At least 19 recordsLinked to original sources
PubMed2001

Nonimaging detectors in drug development and approval.

Regulatory applications for imaging biomarkers will expand in proportion to the validation of specific parameters as they apply to individual questions in the management of disease. This validation is likely to be applicable only to a particular class of drug or a single mechanism of action. Awareness among the world's regulatory authorities of the potential for these emerging technologies is high, but so is the cost to the sponsor (including the logistics of including images in a dossier), and therefore the pharmaceutical industry must evaluate carefully the potential benefit of each technology for its drug development programs, just as the authorities must consider carefully the extent to which the method is valid for the use to which the applicant has put it. For well-characterized tracer systems, it may be possible to design inexpensive cameras that make rapid assessments.

Anesthetics↗
PubMed2001

The Internet: the road to more effective PET.

We may live in the Information Age, but so far information technology (IT) has had little impact on how most nuclear medicine physicians and radiologists practice medicine. Many remain skeptical that IT can improve the care of patients, increase productivity, or enhance income. They fail to recognize that IT is a disruptive technology that will leave behind those who do not embrace it. Although hospital physicians often examine radiographic images and to a lesser degree pathology slides along with the responsible radiologist or pathologist, this collaboration occurs less often than it should in office practice. Teams of radiologists, nuclear medicine physicians, and referring physicians can use the Internet for the high-quality transfer and display of images for simultaneous consultation. People can now be connected electronically in ways never before possible, and in the next generation at speeds that will become a thousand times faster. Nuclear medicine can take advantage of its unique position as an early adopter of digital technology to lead the way as the practice of medicine is changed forever.

Humans↗
PubMed1999

Effect of tracer metabolism on PET measurement of [11C]pyrilamine binding to histamine H1 receptors.

The present study was carried out to investigate the time course of [11C]pyrilamine metabolism and the degree of entry of metabolites into the brain. PET studies were performed in seven healthy volunteers and arterial plasma concentrations of [11C]pyrilamine and its labeled metabolites were determined. After intravenous injection, [11C]pyrilamine metabolized gradually in the human body, with less than 10% of plasma activity being original radioligand at 60 min. Tracer metabolism markedly affected the input function and the calculated impulse response function of the brain. Rat experiments demonstrated that although metabolites of [11C]pyrilamine might enter the brain, they were not retained for prolonged periods of time. At 30-90 min after injection of [11C]pyrilamine, less than 1% of the radioactivity in the brain was originating from metabolites of [11C]pyrilamine. Based on the rat data, the contribution of 11C-labeled metabolites to total [11C]pyrilamine radioactivity in the human brain was estimated and found to be negligible. These results suggest that the metabolites of [11C]pyrilamine do not accumulate within the cerebral extravascular space and that there is minimal metabolism of [11C]pyrilamine by brain tissue itself. Therefore, [11C]pyrilamine metabolites can be neglected in kinetic analysis, using either a compartmental or a noncompartmental model, of the [11C]pyrilamine binding to histamine H1 receptors.

Adult↗
PubMed1999

Assessment of pulmonary lesions with 18F-fluorodeoxyglucose positron imaging using coincidence mode gamma cameras.

UNLABELLED: Accurate assessment of lung carcinoma remains a significant clinical problem, often leading to surgical procedures without curative potential. PET with 18F-fluorodeoxyglucose (FDG) has shown promise in differentiating benign from malignant lesions and in staging the extent of disease, resulting in improved treatment at a significant cost savings. This multicenter prospective study used dual-detector coincidence imaging with FDG to categorize pulmonary lesions as benign or malignant. The goal of this study was to determine the sensitivity and specificity of dual-detector coincidence imaging of FDG in patients with pulmonary lesions who were scheduled to have a diagnostic procedure for histopathologic confirmation. METHODS: A total of 96 patients with pulmonary lesions with a lesion size ranging from 1 to 7 cm with a mean of 3.44 cm based on their chest radiograph or CT scan were studied using FDG scans with a dual-detector coincidence detection system. An additional 24 patients were entered as control subjects. The studies of 120 subjects were interpreted in random order by three physicians experienced in the use of FDG in patients with lung cancer. Surgical pathology was used as the standard for identifying malignant lesions. RESULTS: There was 94% agreement between the readers in the independent interpretation of the FDG studies. In the 96 patients with pulmonary lesions, FDG studies were 97% sensitive and 80% specific in identifying proven malignant lesions. CONCLUSION: The results of this prospective study provide evidence that dual-detector coincidence imaging with FDG provides an accurate, sensitive and specific means of diagnosing malignancy in patients with pulmonary lesions.

Case-Control Studies↗
PubMed1998

Effects of extracellular acetylcholine on muscarinic receptor binding assessed by [125I]dexetimide and a simple probe.

New pharmacologic approaches to enhance brain cholinergic function focus on increasing intrasynaptic acetylcholine. We examined the usefulness of a simple probe and [125I]dexetimide to evaluate in vivo the effects of extracellular acetylcholine on muscarinic receptor binding in the mouse brain. After radiotracer injection continuous time/activity curves were generated over 330 min. [125I]Dexetimide reached a plateau at 90 min post-injection. To increase extracellular acetylcholine, the anticholinesterase physostigmine was administered at 120 min, producing a reversible decrease in [125I]dexetimide specific binding (23%) for 30 min. These findings demonstrate that dynamic changes in extracellular acetylcholine can be evaluated by displacement of [125I]dexetimide binding in vivo using a simple probe system.

Acetylcholine↗
PubMed1998

Autoradiographic and SPECT imaging of cerebral opioid receptors with an iodine-123 labeled analogue of diprenorphine.

The feasibility of imaging cerebral opioid receptors by single photon emission computed tomography (SPECT) has been established in baboon using a novel analog of diprenorphine (DPN) radiolabeled with iodine-123. The radioligand, [123I]-O-IA-DPN (C6-O-[123I]iodoallyl-DPN), was prepared in good yield (80%) with high radiochemical purity (>97%) and high specific radioactivity (>2,400 mCi/micromol). In ex vivo autoradiographic studies, with and without naltrexone blockade, [123I]-O-IA-DPN specifically labeled opioid receptors throughout the mouse brain. Nonmetabolized radioligand accounted for >90% of the signal observed in extracts of whole mouse brain. SPECT imaging trials showed that [123I]-O-IA-DPN selectively localized in regions of baboon brain known to have high densities of opioid receptors, such as striatum, thalamus, and temporal cortex. A much lower level of radioligand uptake and retention was noted for cerebellum, a region with few opioid binding sites. Pretreatment with naltrexone (6.5 pmol/kg) blocked [123I]-O-IA-DPN binding in all brain regions. Using naltrexone blockade to define the nonspecific component for a given region of interest, total to nonspecific binding ratios increased linearly (r > or = 0.98) over the SPECT study with maximal values for striatum (9.8), thalamus (7.1), and temporal cortex (6.9) reached at the last time point investigated (3.5 h). Specific binding for these regions, assessed as the difference between regional SPECT activity for the control and blocked states, proved irreversible over the observation period. By the end of the time course, specific [123I]-O-IA-DPN binding was >85% of total radioactivity in regions rich in opioid receptors and 62% of total radioactivity in cerebellum. The aggregate data are consistent with visualization of multiple opioid receptor types. Thus, [123I]-O-IA-DPN should prove useful for SPECT studies within the constraints imposed by a lack of innate selectivity for a single type of brain opioid receptor.

Animals↗
PubMed1998

Nicotine induced up-regulation of nicotinic receptors in CD-1 mice demonstrated with an in vivo radiotracer: gender differences.

Up-regulation of brain nicotinic receptors (nAChRs) by chronic nicotine treatment has chiefly been demonstrated by in vitro binding assays. Here, we report that up-regulation of nAChRs in CD-1 mice can be detected using a specific in vivo radioligand for nAChRs, [125I]IPH. After 10 days of (-)-nicotine administration, male and female mice demonstrated a significant elevation of [125I]IPH binding in all brain regions studied. [125I]IPH uptake also displayed significant gender differences with male animals showing a more pronounced increase in [125I]IPH accumulation.

Animals↗
PubMed1998

A new look at the cyclotron for making short-lived isotopes. 1966 -classical article-.

This reprint of an article that first appeared in Nucleonics in 1966 provides a unique perspective of the introduction of the cyclotron into clinical medicine and medical research. The cyclotron offers a potentially powerful tool to biomedical centers. With this accelerator one can produce a variety of short-lived nuclides that are unavailable from other sources.

Cyclotrons↗
PubMed1998

A brief history of positron emission tomography (PET).

The development of positron emission tomography (PET) illustrates how advances in basic science translates into benefits for human beings. In 1930 Ernest Lawrence and co-workers conceived of the cyclotron. By 1938 Lawrence, Livingston, et al had designed a "medical cyclotron." The subsequent production of C-11, N-13, O-15, and F-18 found many uses in medical and physiologic research. The introduction of F-18 deoxyglucose represents another major step toward practical clinical use of positron-emitting tracers. We have now achieved the transition from the postulation of the existence of positrons to their use in a wide variety of diseases.

Cyclotrons↗
PubMed1998

5-[I-125/123]lodo-3(2(S)-azetidinylmethoxy)pyridine, a radioiodinated analog of A-85380 for in vivo studies of central nicotinic acetylcholine receptors.

The in vivo biodistribution profile of the novel nicotinic acetylcholine receptor (nAChR) radioligand 5-[I-125/123]Iodo-3(2(S)-azetidinylmethoxy)pyridine, [I-125/123]-5-IA, in mouse brain was examined. This radiotracer displayed good brain penetration (3.1% of the injected dose (ID) in whole brain at 15 min post-radioligand injection). Radioligand distribution was consistent with the density of high affinity nAChRs with highest uptake observed in the nAChR-rich thalamus (14.9 %ID/g at 60 min), moderate uptake in cortex (8.5 %ID/g at 60 min), and lowest uptake in the cerebellum (2.4 %ID/g at 60 min). Pretreatment with several different nAChR agonists (A-85380, (-)-nicotine, cytisine) significantly inhibited [I-125]-5-IA binding in all brain regions studied (P < 0.01) demonstrating the high specificity of the radioligand for nAChRs. Blocking doses of the muscarinic antagonist scopolamine and the non-competitive nAChR channel blocker mecamylamine had no significant effect on radioactive uptake supporting the in vitro selectivity of [I-125]-5-IA for the nAChR component of the cholinergic system. [I-125]-5-IA binding sites were shown to be saturable with unlabeled 5-IA. With a relatively low acute toxicity (LD50 > 3 mg/kg via intravenous injection in mice) and high in vivo specificity and selectivity, 5-IA labeled with the imaging radionuclide I-123 may prove useful for single photon emission computed tomography (SPECT) studies of nAChRs in human subjects.

Alkaloids↗
PubMed1997

A simple probe measures the pharmacokinetics of[125I]RTI-55 in mouse brain in vivo.

A simple external radiation detector system was used to assess brain dopamine and serotonin transporters in mice in vivo using [125I]RTI-55. The results were compared to ex vivo dissection data. Methyl 3beta-(4-iodophenyl) tropane-2beta-carboxic acid methyl ester (RTI-55 or beta-CIT), a high-affinity cocaine antagonist, binds to presynaptic dopamine and serotonin transporters in the brain. Radiotracer accumulation increased for the first 150 min after intravenous injection and then remained constant. When unlabeled RTI-55 was injected, either before or 60 min after radiotracer administration, a significant decrease in tracer accumulation was observed. [125I]RTI-55 binding was also displaced by blocking doses of 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-[3-phenylpropyl]piperazine dihydrochloride (GBR 12909) and paroxetine. The results were similar to the ex vivo dissection data. The results demonstrate the feasibility of using the probe detector system to study the presynaptic transporter system in vivo in the mouse brain. The technique is applicable to other cerebral neurotransmitter systems.

Absorptiometry, Photon↗