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R C Reba

Publications and source records attributed to R C Reba.

At least 91 records · Page 5Linked to original sources
PubMed1985

Relative reactivity of DTPA, immunoreactive antibody-DTPA conjugates, and nonimmunoreactive antibody-DTPA conjugates toward indium-111.

Anti-human serum albumin antibody (Ab) was reacted with cyclic DTPA dianhydride (cDTPAA) at various cDTPAA/Ab molar ratios between 1 and 40. Using a carrier In titration method for DTPA and DTPA-antibody conjugate (Ab-DTPA), we determined that the above reactions produced between 0.1 and 11 DTPA molecules per either immunoreactive antibody (sAb) or nonimmunoreactive antibody (nAb). The percentage of sAb remaining after the above reactions was between 88 and 62%. The reaction of no-carrier-added 111In with the reaction mixture from cDTPAA/Ab molar ratios of 1 to 40 gave radiochemical yields less than or equal to 25% for the respective Ab-DTPA. The rest of the 111In activity was associated with free DTPA. Our results indicate that Ab-DTPA containing greater than 1 DTPA molecule per Ab is more reactive than that containing less than 1 DTPA but is about as reactive as free DTPA. This allows us to label in the presence of free DTPA and consequently prevent colloid formation. The percentage of 111In activity incorporated into sAb-DTPA from the reactions at these molar ratios was similar to that found from the uv analysis. This indicates that the reactivity of sAb-DTPA and nAB-DTPA from the same conjugation reaction is similar. As a result, we were able to conjugate about one DTPA molecule to the Ab without causing deactivation of the Ab and label it with 111In in the presence of excess DTPA. We obtained a specific activity of 6 muCi 111In per microgram of Ab using research grade 111In without further purification.

Antibodies↗
PubMed1985

Use of 3-quinuclidinyl 4-iodobenzilate as a receptor binding radiotracer.

3-Quinuclidinyl 4-iodobenzilate was shown to bind to the muscarinic acetylcholine receptor (mAChR) by testing the saturability and the stereoselectivity in the corpus striatum, cerebellum, and the heart. But the ratio of radioactivity in tissues containing different concentrations of mAChR was less than the ratio of mAChR concentrations determined by in vitro saturation assay. As a result, the sensitivity to change in receptor concentration by external imaging will be reduced for this receptor binding radiotracer.

Animals↗
PubMed1984

Exercise radionuclide ventriculographic responses in hypertensive patients with chest pain.

The effectiveness of exercise-treadmill testing in diagnosing coronary-artery disease in hypertensive patients is limited by a high rate of false positivity. Exercise radionuclide ventriculography, however, relies on different criteria (ejection fraction and wall motion), and we have evaluated this procedure in 37 hypertensive and 109 normotensive patients with chest pain, using coronary arteriography as an indicator of coronary disease. In the hypertensive cohort there was no difference in the ejection fraction at rest between the 17 patients with coronary disease and the 20 without it. Neither group had a significant mean (+/- S.E.M.) change in ejection fraction from rest to exercise (-1.9 +/- 2 and - 1.4 +/- 1 per cent, respectively). A wall-motion abnormality developed during exercise in 5 of the 17 hypertensive patients with coronary disease (29 per cent) and in 4 of the 20 without it (20 per cent) (P = not significant). In the normotensive cohort, however, the peak-exercise ejection fractions were significantly different. The 71 patients with coronary disease had a mean decrease of 3.6 +/- 1 per cent, in contrast to the patients without coronary disease, who had an increase of 6 +/- 1 per cent (P less than 0.001). An exercise-induced wall-motion abnormality was seen in 35 of the 71 patients with coronary disease (48 per cent), as compared with 3 of the 38 without it, (8 per cent) (P less than 0.001). We conclude that exercise radionuclide ventriculography is inadequate as a screening test for coronary atherosclerosis in hypertensive patients with chest pain.

Adult↗
PubMed1984

[125I] 3-quinuclidinyl 4-iodobenzilate: a high affinity, high specific activity radioligand for the M1 and M2-acetylcholine receptors.

We have prepared a radioiodinated ligand which binds with high affinity to the muscarinic acetylcholine receptor (m-AChR). A derivative of 3-quinuclidinyl benzilate, [125I] labeled (R) 1-aza-bicyclo(2.2.2)oct-3-yl (R,S)-alpha-hydroxy-alpha-(4-[125I]iodophenyl)phenyl acetate (4- IQNB ) exhibits an affinity for the m-AChR from corpus striatum higher than that of (R) [3H] QNB. Additionally, [125I] 4- IQNB exhibits receptor selectivity for the M1 receptor since the affinity for the receptor from dog and rat heart is lower than that using dog or rat corpus striatum.

Animals↗
PubMed1984

External imaging of cerebral muscarinic acetylcholine receptors.

A radioiodinated ligand that binds to muscarinic acetylcholine receptors was shown to distribute in the brain by a receptor-mediated process. With single-photon-emission imaging techniques, radioactivity was detected in the cerebrum but not in the cerebellum, whereas with a flow-limited radiotracer, radioactivity was detected in cerebrum and cerebellum. Single-photon-emission computed tomography showed good definition of the caudate putamen and cortex in man.

Animals↗
PubMed1984

In vivo competition studies with analogues of 3-quinuclidinyl benzilate.

Among ligands that bind to the alpha- and beta-adrenoceptors and to the muscarinic acetylcholine receptor (m-AChR), those that bind to the latter have the best properties for external detection of receptor sites by gamma-camera imaging. To develop the optimal radiotracer, nonradioactive analogues of 3-quinuclidinyl benzilate (I) were tested in in vivo displacement studies with (-)-[3H]I to determine their ability to compete with (-)-[3H]I for the muscarinic acetylcholine receptor. There is a linear correlation between the ability to compete with (-)-[3H]I for the m-AChR and the affinity constant of the analogue as determined by in vitro assay, suggesting that the test is a valid indicator of in vivo distribution. One radioiodinated analogue, 3-quinuclidinyl p- iodobenzilate , bound to m-AChR in the heart and brain of rats.

Animals↗
PubMed1984

Synthesis and evaluation of radioiodinated derivatives of 1-azabicyclo[2.2.2]oct-3-yl alpha-hydroxy-alpha-(4-iodophenyl)-alpha- phenylacetate as potential radiopharmaceuticals.

Two derivatives of (RS)-1-azabicyclo[2.2.2]oct-3-yl (RS)-alpha-hydroxy-alpha-(4-iodophenyl)-alpha-phenylacetate (1a) and three partially resolved (R)- or (S)-1-azabicyclo[2.2.2]oct-3-yl (RS)-alpha-hydroxy-alpha-(4-iodophenyl)-alpha-phenylacetates labeled with no carrier added iodine-125 (1b, 18, and 19) and iodine-123 (1c and 18a) were synthesized by the Wallach triazene approach. We have found that this approach is necessary to obtain no carrier added labeling and gives far better results than the direct electrophilic iodination. The obtained yields were 7 to 18% when using iodine-123 (yield dependent on the source of iodide) and up to 17% for iodine-123 (yield dependent on the source of iodide) and up to 17% for iodine-125 labeled compounds. Our preliminary distribution studies indicate that 1b localizes in the organs known to have a large concentration of muscarinic receptors and that this localization is due to binding to those receptors.

Animals↗
PubMed1984

Synthesis and evaluation of (17 alpha,20E)-21-[125I]iodo-19-norpregna-1,3,5(10),20-tetraene-3,17 -diol and (17 alpha,20E)-21-[125I]iodo-11 beta-methoxy-19-norpregna-1,3,5(10),20-tetraene-3,17-diol (17 alpha-(iodovinyl)estradiol derivatives) as high specific activity potential radiopharmaceuticals.

Two 17 alpha-[125I]iodovinyl estradiol derivatives 4b,d possessing high specific activity have been prepared and tested as potential radiopharmaceuticals. The use of the 3-acetyl derivatives 2c,e and the replacement of iodine monochloride with sodium iodide and Chloramine-T in THF/phosphate buffer (pH 7.0) permitted us to synthesize no-carrier-added (17 alpha,20E)-21-[125I]iodo-19-norpregna-1,3,5(10),20-tetraene-3,17-d iol (4b) and (17 alpha,20E)-21-[125I]iodo-11 beta-methoxy-19-norpregna-1,3,5(10),20-tetraene-3,17-diol (4d) with 50% radiochemical yield and high purity. Although the specific activity represents only half of the theoretical value in some cases, this modified approach is a substantial improvement over the previously published method. Our preliminary distribution studies indicate that although both 4b and 4d localize in the tissues known to have a large concentration of estrogen receptors, 4d accumulates in higher amounts in target tissues and provides a high target to nontarget ratio.

Animals↗
PubMed1984

Labeling monoclonal antibodies and F(ab')2 fragments with (111In) indium using cyclic DTPA anhydride and their in vivo behavior in mice bearing human tumor xenografts.

Monoclonal antibodies (MAb) and their F(ab')2 fragments to human colorectal carcinoma (CRC) and human melanoma-associated antigens were conjugated to diethylenetriaminepentaacetic acid (DTPA) via an acylation reaction using cyclic DTPA dianhydride. Relative immunoreactivity of the F(ab')2 fragments was as high as 70% when an average of only 0.7 DTPA molecules was conjugated per fragment, decreasing rapidly to less than 5% when 9.0 DTPA molecules were conjugated. The 111In-labeled whole MAb in mice bearing human tumor xenografts showed higher concentrations in tumor, liver, kidney, and spleen 7 days after injection of MAb when compared with the same MAb labeled with 131I. F(ab')2 labeled with 111In showed a marked persistence in the tumor-bearing mice with higher concentrations in all organs except blood, when compared with 131I-labeled F(ab')2. Radioactivity was particularly high in the kidneys. Although images of human tumor xenografts were easily visualized using 131I-labeled F(ab')2 3 days after injection, it was difficult to visualize tumor grafts with 111In-labeled F(ab')2 due to persistently high renal, liver, and background activity. Increased catabolism of the 131I-labeled MAb may be the cause of the difference; but antibodies with high immunological activity are a necessity for in vivo imaging studies before firm conclusions can be drawn.

Animals↗
PubMed1984

[I-125] 17 alpha-Iodovinyl 11 beta-methoxyestradiol: in vivo and in vitro properties of a high-affinity estrogen-receptor radiopharmaceutical.

17 alpha-[125I[Iodovinyl 11 beta-methoxyestradiol ([I-125]MIVE2) has been prepared with high specific activity (1500-2000 Ci/mmol) and a high affinity for the estrogen receptor (KA = 6.8 x 10(9) M/Ml). In vivo distribution studies using immature rats result in high levels of activity in the uterus (20-30% dose/g) with uterus-to-plasma ratios on the order of 68 to 100. Peak activity in the uterus is obtained between 2 and 4 hr, and by 6 hr 50% of the activity has washed out. The [I-125]MIVE2 exhibits a slower rate of washout relative to the washout of H-3 estradiol. By in vivo competition studies with nonradioactive estradiol, we found that 95% of the [I-125]MIVE2 bound in the uterus is specifically bound to estrogen receptors. The radioactive labeling of MIVE2 is sufficiently rapid so that [I-123]MIVE2 has been synthesized and is currently in clinical trials. These results suggest that MIVE2 would be an excellent agent for the study of estrogen receptors in vivo and in vitro.

Animals↗
PubMed1984

The characteristics of I-125 4-IQNB and H-3 QNB in vivo and in vitro.

The accumulation of (R)-(H-3)-3-quinuclidinyl benzilate (H-3 QNB) and (R,S)-1-azabicyclo(2.2.2)oct-3-yl (R,S)-alpha-hydroxy-(4-[I-125]iodophenyl) benzeneacetate (I-125 4- IQNB ) in heart, caudate/putamen, and cerebellum of rats was determined at intervals from 15 min to 4 hr after injection. The behavior of the two radiotracers in the heart is consistent with in vitro results with respect to affinities and specificities. In the brain, however, the compounds differ in tissue selectivity. At high specific activity, neither compound provides localization that is consistent with the concentration of receptor in the tissues. The results of this study do not indicate quantification of receptor concentration by means of single external images.

Animals↗
PubMed1983

Differences in affinities of muscarinic acetylcholine receptor antagonists for brain and heart receptors.

The affinities of atropine, scopolamine, 3-quinuclidinyl benzilate and twelve analogues of 3-quinuclidinyl benzilate were determined for the muscarinic acetylcholine receptor (m-AChR) using membrane preparations from caudate/putamen. The affinity constants thus obtained were compared with affinities previously reported for the m-AChR obtained from ventricular muscle. The affinities differed significantly for six of the compounds, the largest difference being 16-fold. Neither solubilization nor variation of physiologically significant salts led to a significant change in the affinity of that compound. These results are interpreted as supporting the subclassification of the muscarinic acetylcholine receptor.

Animals↗
PubMed1983

Discordant Tc-99m sulfur colloid and In-113m chloride blood pool images in patients with acute amebic liver abscess.

Using combined Tc-99m sulfur colloid and In-113m chloride eluate imaging, studies from 32 patients with proven amebic liver abscess were analyzed. The results revealed good perfusion of the amebic lesion in three, poor perfusion in 11, and absent perfusion in 18. These results appear to depend on abscess size and age. Images with In-113m seem to be better than those with Tc-99m sulfur colloid in depicting amebic liver abscess during antiamebic therapy. Overall, the In-113m images provide more precise information concerning abscess size and shape.

Acute Disease↗