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T Qu

Publications and source records attributed to T Qu.

29 records · Page 2Linked to original sources
PubMed1997

Technetium-99m labeled epidermal growth factor-tumor imaging in mice.

We have shown previously that the epidermal growth factor peptide (EGF) may be radiolabeled with 99mTc at room temperature and neutral pH by using the N-hydroxysuccinimide ester of S-acetyl mercaptoacetyltriglycine (MAG3) as a bifunctional chelator. By a competition binding assay, we found that MAG3-conjugated EGF retained biological activity. Furthermore, the labeled peptide exhibited saturation binding to EGF receptor-positive tumor cell lines which could be inhibited by presaturation of the cells with unlabeled, native EGF. Biodistribution in normal mice at 3 h postadministration showed rapid clearance with minimal retention of the label in sampled organs. We have now investigated the tumor localization properties in mice of this labeled peptide. Nude mice implanted with the EGF receptor-positive tumors A431 and LS-174T were administered labeled EGF and a labeled control peptide (BPTI, aprotinin). Tumor uptake at 12 h postadministration was 0.44% injected dose/g for EGF/g vs. 0.09 for the control. Pretreatment of tumored mice with unlabeled EGF blocked about half the tumor uptake. Animals were also administered an anti-EGF receptor antibody labeled with 99mTc via MAG3. Relative to the antibody, tumor-to-muscle ratios were improved from 6 to 15 and tumor-to-blood ratios from 0.4 to 7 with EGF. These favorable results along with documented evidence of overexpression of the EGF receptor in many human tumors suggest that 99mTc-EGF should be considered further for tumor detection.

Animals↗
PubMed1997

In vivo hybridization of technetium-99m-labeled peptide nucleic acid (PNA).

UNLABELLED: Hybridization of a radiolabeled single-stranded DNA oligonucleotide with its single-stranded complement in vivo has not yet been convincingly demonstrated. A contributing factor may be unfavorable in vivo properties of the phosphodiester and phosphorothioate DNAs. Peptide nucleic acid (PNA) oligomers have been reported to possess in vivo properties more suitable for radiopharmaceutical applications. METHODS: We have radiolabeled an amine-derivatized 15-base PNA oligomer with 99mTc through a modified MAG3 chelator. RESULTS: The ability of the PNA to hybridize in vitro with its complement appeared to be unimpaired after conjugation and radiolabeling. Size-exclusion, high-performance liquid chromatography (HPLC) analysis of 37 degrees C serum after 24 hr of incubation showed the radiolabel to be present predominately as labeled PNA with indications of labeled serum proteins and a low molecular weight catabolite. Whole-body clearance in mice was rapid, with 50% of the label eliminated in about 2 hr. After 2.5 hr, the highest uptake (kidneys) was only 1.5% of the injected dose/g; less than 0.07%/g was present in all sampled tissues at 24 hr. To evaluate in vivo hybridization, beads were implanted subcutaneously in both thighs of normal mice. In the left thigh only, the beads were conjugated with complementary single-stranded PNA. At 23 hr following intraperitoneal administration of the labeled PNA, the left/right thigh radioactivity ratio was 6:1. Whole-body images at this time showed only bladder, kidneys and the left thigh. CONCLUSION: Unlike the radiolabeled DNAs investigated in this laboratory, 99mTc-PNA displays stability and pharmacokinetic properties suitable for eventual use as radiopharmaceuticals.

Animals↗
PubMed1996

Fluoro-Green and Fluoro-Red: two new fluorescent retrograde tracers with a number of unique properties.

As a means of improving nerve tract-tracing in the peripheral and central nervous systems we experimented with two (retrograde) fluorescent emulsions, which we have tentatively named Fluoro-Green (FGr) and Fluoro-Red (FRe), and which we believe possess the following seven advantages: (1) they show little diffusion beyond the injection site; (2) their excitation/emission characteristics allow their use in double-tracing experiments; (3) they do not 'leak' from labeled cells; (4) their fluorescence is presented as large granules in the cytoplasm and its processes; (5) the fluorescence lasts for a sufficiently long time to permit repeated observation; (6) they may be used in combination with a wide variety of other neuroanatomical tracing methods; (7) they are economical, non-toxic and easy to utilize.

Animals↗
PubMed1996

Retrograde fluorescent double-labeling study of bilaterally projecting retinal ganglion cells in albino rats at different stages of development.

Injection of the fluorescent tracers 10% Evans blue (EB) and 4% fluoro-gold (FG) into the right and the left dorsal lateral geniculate nucleus, respectively, of albino rats at different stages of development demonstrated the presence of double-labeled retinal ganglion cells that projected bilaterally into both the dorsal lateral geniculate nuclei (dLGN). Findings confirmed that the distribution of these double-labeled cells was gradually reduced after birth, being confined to the peripheral temporoventral quarter (temporal-ventral crescent) of the retina after postnatal day 15. We estimated the proportion of double-labeled cells to total labeled cells in the same area at different stages of development (0-90 days); values ranged from 35.3% in the neonate to 5.27% in the adult rat which suggests that the majority of double-labeled cells and/or their axons were lost early in development. That a small number of ganglion cells were observed to project bilaterally in the adult rats suggested that these cells conduct the same visual information to both hemispheres throughout the animal's life.

Animals↗
PubMed1996

Demonstration of direct input from the retina to the lateral habenular nucleus in the albino rat.

The projection from the retina to the habenular complex was studied using fluorescent retrograde tracers in the albino rat (Wistar, Japan Clea). Following separate unilateral injections of Fluoro-Gold (FG), Fluoro-Ruby (FR), or 4-acetamido,4- isothiocyanostilbene-2,2'-disulfonic acid (SITS) into the lateral habenular nucleus (LHB), a small population of ganglion cells was labeled sporadically, predominantly those in the nasal retina contralateral to each injection site. Most of them were small cells, ranging from 9 to 16 mu m in diameter, roughly corresponding to the type III ganglion cell in the rat retina. Additionally, all of the structures previously described as regions projecting to the LHB were confirmed. Upon re-examination of previous brain sections of albino rats which had undergone monocular enucleation, degenerating retinal nerve axons and/or their terminals, stained by a modified selective silver impregnation method, were observed in the well-documented end regions of retinal afferents as well as the LHB. The degenerating retino-habenular nerve terminals were distributed sparsely and restricted mainly to the caudal part of the LHB contralateral to the side of ocular enucleation. The present experimental data provide evidence for the existence of a non-image forming retino-habenular pathway in the albino rat. We suggest that, besides serving as a point of convergence for some of the major conduction channels of the limbic and striatal systems, the LHB may play more general integrative roles, including participation in the integration of visual information.

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗
PubMed1996

Technetium-99m antibodies labeled with MAG3 and SHNH: an in vitro and animal in vivo comparison.

The in vitro stability and animal pharmacokinetics of 99mTc bound to Sandoz and C110 IgG antibodies via a modified MAG3 has been compared with the hydrazino nicotinamide (SHNH) moiety as standard. For both antibodies, the stabilities of the label to challenge at up to 50:1 cysteine: IgG molar ratio were comparable, but at higher molar ratios, MAG3 showed greater instabilities. For the Sandoz antibody, size-exclusion HPLC analysis of 37 degrees C serum incubates and plasma samples from injected mice showed no clearly distinguishable differences. In the C110 case, some increased high molecular weight radioactivity was apparent with MAG3. Biodistributions in normal mice showed significant differences only in liver (Sandoz) and liver, spleen, intestines, stomach, and blood (C110), with SHNH usually providing higher levels. Thus, for two different antibodies and under the conditions of this study, the MAG3 chelator provided a 99mTc label with properties similar to that of SHNH moiety.

Animals↗
PubMed1995

Bifurcated projections of retinal ganglion cells bilaterally innervate the lateral geniculate nuclei in the cat.

Cats were injected with the fluorescent retrograde tracers, Fluoro-Gold (FG) and Evans Blue (EB), into the left and right lateral geniculate nuclei (LGN), respectively. About 4.56% of the ganglion cells in the temporal retina were double-labeled by these dyes. 4.7% of these cells were of the large type, 30.3% were of the medium type, and 65% were classified as cells of the small type. These results indicate that members of all three ganglion cell size classes, mainly those of small type, bilaterally innervate the LGN via axonal bifurcation.

Animals↗
PubMed1995

Bifurcating projections from the retinal ganglion cells to the primary visual targets (SC and LGN) in the cat.

Bifurcating projections of retinal ganglion cells to the primary visual targets were studied in the cat using a retrograde fluorescent double-labeling technique with Fluoro-Gold (FG) and Evans Blue (EB) as the tracers. Following injections of FG and EB into the left and right lateral geniculate nuclei (LGN), or into the left and right superior colliculi (SC), or LGN and SC on the same side, 4.56% of the single-labeled cells with one tracer were simultaneously labeled by the other tracer injected contralaterally in bilateral LGN-injection group; 12.18% of the single-labeled cells were further labeled by the other tracer injected contralaterally in bilateral SC injection-group; and 8.95% of the single-labeled cells in the ipsilateral retina, 10.94% of the single-labeled cells in the contralateral retina by the tracer injected into the LGN were labeled by the other tracer injected into the SC on the same side. All three retinal ganglion cell classes by size demonstrated double-labeled cell bodies. In the bilateral LGN- and bilateral SC-injection groups, the double-labeled cells were mainly of the small type (65% and 82.8%, respectively), while in the group of the injections into the LGN and SC on the same side, double-labeled cells were predominantly of the large type (55.45%). These results indicate that single ganglion cells of the retina send bifurcated projections to the bilateral LGN, bilateral SC, or unilateral LGN and SC, via axonal collaterals. These bifurcated axons can be regarded as an important way by which the information of the single ganglion cells can be conducted to the same primary visual targets on both sides, and two different optic centers on the same side of the brain.

Animals↗
PubMedDate not supplied

Inflammatory 5-LOX mRNA and protein are increased in brain of aging rats.

5-Lipoxygenase (5-LOX) is the key enzyme in the synthesis of leukotrienes, inflammatory mediators of arachidonic acid. 5-LOX is also expressed in neurons (in particular in the hippocampus and the cerebellum), and it seems to be capable of promoting neurodegeneration. Recently, we observed greater 5-LOX mRNA content in the hippocampus of older (24 months) than younger (2 months) rats. In this study, we measured in the hippocampus and the cerebellum of younger and older male F344 rats the contents of: 5-LOX mRNA, FLAP (5-LOX activating protein) mRNA, and 5-LOX protein. By using a quantitative reverse transcription/polymerase chain reaction (PCR) (RT-PCR) with internal standards we found that 5-LOX but not FLAP mRNA content is greater (both in hippocampus and cerebellum) of older than younger rats. By using quantitative Western immunoblotting, we found a greater content of 5-LOX protein in the hippocampus and the cerebellum of older rats; we also established that the membrane/cytosol 5-LOX content ratio is larger in the brains of older than younger rats (statistically significant in the cerebellum). The latter can be considered an indication of 5-LOX translocation/activation during aging. Together these results suggest that aging increases both neuronal 5-LOX expression and protein translocation, and indicate that the 5-LOX system might play a significant role in the pathobiology of aging-associated neurodegenerative diseases.

5-Lipoxygenase-Activating Proteins↗