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T J Hoffman

Publications and source records attributed to T J Hoffman.

16 recordsLinked to original sources
PubMed1992

The effect of ligand structure on glutathione-mediated decomposition of propylene amine oxime derivatives.

Tetramethylpropyleneamine oxime (TMPAO) was synthesized and complexed to 99mTc. 99mTc-TMPAO samples, when challenged with reduced glutathione (GSH), were shown to have two GSH sensitive components, similar to a mixture of d,l and meso 99mTc-HMPAO. One component had a GSH-induced second-order dissociation rate constant (K2) similar to 99mTc-meso-HMPAO. Despite the presence of a large fraction of this component in these samples, brain uptake and autoradiographic studies with 99mTc-TMPAO were equivalent to 99mTc-d,l-HMPAO suggesting that both the d,l and meso 99mTc-TMPAO isomers are efficiently trapped in brain.

Animals↗
PubMed1992

Radiographic and neuro-SPECT imaging in an immature third ventricle teratoma: case report.

We report a case of an immature teratoma of the third ventricle, which was preoperatively thought to be a choroid plexus papilloma. The diagnosis was made by biopsy since the radiographic (CT, MRI), angiographic and scintigraphic findings ([99mTc]pertechnetate, 99mTc-DTPA, 99mTc-HMPAO brain SPECT) were nonspecific. Disruption of the blood-brain barrier is the mechanism for radionuclidic and contrast tumoral uptake and is demonstrated by marked contrast enhancement on CT and focal concentration on [99mTc]pertechnetate and 99mTc-DTPA images. No suppression of [99mTc]pertechnetate tumor uptake was observed following the administration of potassium perchlorate. Increased concentration of tumor protein is suggested by the increased signal on the T1-weighted magnetic resonance images and high [99mTc]pertechnetate uptake. The tumor's detection on the 99mTc-HMPAO brain SPECT was due to its intraventricular location. A number of potential mechanisms for brain tumor localization of 99mTc-HMPAO are discussed.

Cerebral Ventricle Neoplasms↗
PubMed1988

Retention of [99mTc]-d,l-HM-PAO in rat brain: an autoradiographic study.

The regional cerebral distribution pattern of [99mTc]-d,l-HM-PAO in rat brain was studied by autoradiography. The regional cerebral uptake of this tracer is related to regional cerebral blood flow (rCBF); however, the ratio of retained radioactivity (determined by digital imaging techniques) in gray matter compared to white matter is lower than that reported for the blood flow ratio. Considerable inhomogeneity is observed in cortical gray matter for at least 60 min postinjection, demonstrating that minimal, if any, cerebral redistribution of this agent occurs.

Animals↗
PubMed1988

Microcomputer-based digital image analysis system for quantitative autoradiography.

A computerized image processing system utilizing an IBM-XT personal microcomputer with the capability of performing quantitative cerebral autoradiography is described. All of the system components are standard computer and optical hardware that can be easily assembled. The system has 512 horizontal by 512 vertical axis resolution with 8 bits per pixel (256 gray levels). Unlike other dedicated image processing systems, the IBM-XT permits the assembly of an efficient, low-cost image analysis system without sacrificing other capabilities of the IBM personal computer. The application of this system in both qualitative and quantitative autoradiography has been the principal factor in developing a new radiopharmaceutical to measure regional cerebral blood flow.

Animals↗
PubMed1987

Two populations of tyrosine hydroxylase-positive cells occur in the spinal cord of the chick embryo and hatchling.

The existence of tyrosine hydroxylase (TH)-containing neurons in the spinal cord of the chick embryo was investigated by anti-TH immunocytochemistry. Two populations of intensely immunostained cells were observed along the entire extent of the cord, beginning late in chick embryogenesis. One group of TH-positive cells was particularly numerous and found ventral to the central canal. The other group, which was smaller in number, was located along the superficial and lateral border of the dorsal horn of the spinal cord. When examined by the glyoxylic acid histofluorescence technique, cells could be visualized only very infrequently ventral to the central canal, and not at all within the dorsal horn. However, after pretreatment of hatchlings with the catecholamine synthesis precursor L-DOPA, cells ventral to the canal were readily observed by histofluorescence, while the dorsally located cells seldom visualized. Since these populations of TH-positive cells appear to only partially express the catecholaminergic phenotype, these cells may provide a model in which factors regulating the expression of neurotransmitter phenotypes can be examined in neurons of the developing CNS.

Animals↗
PubMed1986

Analysis of the change in number of serotonergic neurons in the chick spinal cord during embryonic development.

The existence of serotonin (5-HT)-containing neurons in the spinal cord of the chick embryo was examined by anti-5-HT immunocytochemistry. The first immunoreactive cells were observed in embryos at 7 days of incubation (E7) and were initially located within the floor plate of the early spinal cord. By E9, immunostained cells occurred throughout the length of the spinal cord and were frequently encountered in most transverse sections of the cord. When examined at later embryonic ages of E12, 17 and at hatching (E21 or 22), the 5-HT cells became progressively more difficult to find with the advancing age of the embryos. To determine if this population of spinal cord 5-HT neurons actually diminished during development, a detailed quantitative analysis was undertaken to estimate the number of 5-HT cells in the cord of chick embryos at different ages. The results of this investigation demonstrated that the size of the 5-HT neuronal population rose rapidly from E7 and plateaued (at approximately 3500 neurons) between E9 and E12. As anticipated, the number of 5-HT cells at E17 decreased at all cord levels. Surprisingly, however, the number of spinal cord 5-HT neurons at hatching increased (depending on the cord level) either back to, or above, the counts estimated for the earlier ages of E9 and E12. Therefore, cells expressing the 5-HT phenotype in the spinal cord of the chick embryo persist throughout the period of embryonic development, rather than appear transiently.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Cerebral uptake and retention of 99Tcm-hexamethylpropyleneamine oxime (99Tcm-HM-PAO).

A new radiopharmaceutical, 99Tcm-hexamethylpropyleneamine oxime (99Tcm-HM-PAO) is described. This agent displays considerable promise for imaging cerebral blood flow. In studies in rats and one human volunteer, 99Tcm-HM-PAO demonstrates good brain uptake, prolonged retention of activity in the brain, and slow regional redistribution. These properties suggest that this new radiopharmaceutical is ideal for single photon emission tomographic (SPECT) imaging of cerebral blood flow.

Animals↗
PubMed1984

99mTc-propylene amine oxime (99mTc-PnAO); a potential brain radiopharmaceutical.

Propylene amine oxime (PnAO) forms a neutral lipid soluble complex with 99mTc. 99mTc-PnAO can be prepared by simple reduction of 99mTc-pertechnetate with stannous ion in the presence of excess PnAO in saline at or near neutral pH. This agent will passively penetrate biological membranes including the intact blood-brain barrier (BBB) as evidenced by the high brain uptake observed shortly after IV injection. The first-pass extraction efficiency in baboons was estimated to be 80% at normal blood flow. This agent or a derivatized form of 99mTc-PnAO may be useful in assessment of regional cerebral blood flow (rCBF) in humans.

Animals↗
PubMed1984

A neutral lipophilic complex of 99mTc with a multidentate amine oxime.

Propylene amine oxime, 3,3'-(1,3-propanediyldiimino)bis(3-methyl-2-butanone)dioxime, (PnAO) forms a neutral lipophilic complex with 99mTc in greater than 95% yield at room temperature at pH 5-10. The complex can be prepared with generator produced 99mTc using 10(-5) M SnC4H4O6 as the reducing agent at ligand concentrations as low as 3 X 10(-5) M. It is stable in saline solutions for as long as 24 h. [99mTc]PnAO may be useful as an imaging agent which passively diffuses across the blood brain barrier.

Brain↗
PubMed1984

The behavior of neutral amine oxime chelates labelled with Tc at tracer level.

Neutral 99mTc-chelates were formed with propylene amine oxime, 3,3'-(1,3-propanediyldiimino)bis-(3-methyl-2-butanone)-dioxime and other PnAO analogues. Even though the other amine oxime ligands form neutral chelates with 99mTc, the stability, lipophilic and the brain uptake characteristics are less desirable than [99mTc]-PnAO. These results demonstrate that slight modifications in the amine oxime ligand backbone produces significant effects on the chemical and biological behavior of the [99mTc]dioxime chelates.

Animals↗
PubMed1984

Biodistribution of lipophilic 99mTc complexes of cyclam derivatives.

Several n-alkyl-cyclam derivatives were synthesized which form stable single component cationic chelates with 99mTc. These results suggest that the cyclam moiety in these derivatives complexes 99mTc in the same manner as the underivatized macrocycle. Biodistribution studies in mice show that all of these chelates are cleared from circulation by both the kidneys and liver. The ratio and rates of clearance by these organ systems is related to lipid solubility. None of the lypophilic-cationic-99mTc agents show any significant myocardial uptake. Also, these chelates show no significant ability to penetrate the blood-brain-barrier.

Animals↗
PubMedDate not supplied

Evaluation of alkylated derivatives of 99mTc-propylene amine oxime (99mTc-PnAO).

Several lipophilic di-alkylated derivatives of propylene amine oxime (PnAO were complexed to 99mTc. Assessment of the 99mTc-PnAO derivatives included biodistribution and qualitative autoradiography. All of the derivatives studied penetrated the intact blood-brain-barrier, with the 99mTc-dibutyl-PnAO complex exhibiting the lowest initial brain uptake while the 99mTc-diethyl-PnAO and the 99mTc-dipropyl-PnAO complexes possessing nearly identical initial brain uptake as compared to 99mTcPnAO. Qualitative autoradiographs revealed significant loss of image resolution with extended time post injection indicative of rapid radiopharmaceutical washout. Although increasing alkyl chain length did not enhance initial brain uptake, the data demonstrates that limited modification of the PnAO ligand structure can be performed without decreasing cerebral uptake of the respective 99mTc complex.

Animals↗
PubMedDate not supplied

Formation of a stable 99mTc-tri-hydrazidophosphine oxide (99mTc-THP) chelate.

Atri-hydrazidophosphine oxide (THP) ligand was synthesized and used to complex 99mTc in high yield (> 95%) by Sn(II) reduction of 99mTcO4-. 99mTc-THP has excellent stability in both 0.9% acqueous NaCl at neutral pH and in human serum at 37 degrees C. Biodistribution studies indicate minimal organ specificity and no significant in vivo release of 99mTcO4-. The ease of 99mTc complexation with THP and the high stability of 99mTc-THP suggests that this ligand may be used as a basis for the development of new imaging agents.

Animals↗