Biomedical subjects

D R Hwang

Publications and source records attributed to D R Hwang.

28 records · Page 2Linked to original sources

PubMed1990

N-(3-[18F]fluoropropyl)-N-nordiprenorphine: synthesis and characterization of a new agent for imaging opioid receptors with positron emission tomography.

A series of N-fluoroalkyl (1-5) and N-alkyl (6-8) analogues of the high-affinity opioid receptor antagonist diprenorphine (9) has been synthesized and evaluated with in vitro binding assays. Three of the N-fluoroalkyl compounds were prepared with the positron-emitting radionuclide 18F (1a, 2a, 5a), and their biodistribution was determined in rats. Compounds 2a and 5a were made by using a two-step labeling procedure, [18F]fluoride displacement of an iodoalkyl triflate followed by N-alkylation, that required 2 h and proceeded in 4-6% overall radiochemical yield at the end of synthesis. The effective specific activity of compounds 2a and 5a, determined by competitive receptor binding assay, was 840-1820 Ci/mmol. Compound 1a was made by the same two-step procedure, with the bromoalkyl triflate, in 0.3-0.6% radiochemical yield at an effective specific activity of 106-264 Ci/mmol. Specificity of binding in vivo was measured as the percent injected dose/gram of striatal tissue divided by the percent injected dose/gram of cerebellar tissue. The best striatum to cerebellum ratio (3.32 +/- 0.74 at 30 min) was achieved with N-(3-[18F]-fluoropropyl)-N-nordiprenorphine (2a, [18F]FPND). The high specific binding demonstrated by this compound indicates that it may be useful for in vivo imaging of opioid receptors with positron emission tomography.

Animals↗

PubMed1989

No-carrier-added synthesis of 3-[18F]fluoro-1-(2-nitro-1-imidazolyl)-2-propanol. A potential PET agent for detecting hypoxic but viable tissues.

Four different approaches towards the synthesis of [18F]FMISO have been studied. The first approach was based on the reaction of epoxide 4 and [18F]fluoride. Both specific activity and radiochemical yield (less than 1%) for [18F]FMISO were low. Two new approaches, starting with compounds 8 and 9, have failed to give [18F]FMISO. The fourth approach, based on the reaction of [18F]epifluorohydrin 10, prepared from Tosylate 13 and [18F]KF/Kryptofix 222, has provided a reliable, no-carrier added synthesis of [18F]FMISO. The product was obtained in a radiochemical yield of 7-12% at end-of-synthesis (based on [18F]fluoride) with a specific activity of greater than 400 Ci/mmol and a synthesis time of 1.5 h. Preliminary PET studies suggest that [18F]FMISO may be a promising tracer for delineation of ischemic but viable myocardium.

Fluorine Radioisotopes↗

PubMed1989

N-3-[18F]fluoropropylputrescine as potential PET imaging agent for prostate and prostate derived tumors.

A potential PET imagining agent for prostate and prostate derived tumors, N-3-[18F]fluoropropylputrescine, has been prepared. The radiochemical yield was 7-10% at end-of-synthesis (EOS) and the specific activity was greater than 1.1 Ci/mumol (overall synthesis time was 1.5 hr). In vivo biodistribution in mature male rats showed high prostate uptake. In rats that were pretreated with alpha-difluoromethylornithine and dihydrotestosterone propionate, the prostate to muscle ratio and prostate to blood ratio increased significantly. This high target uptake and target to nontarget ratio indicates the potential of this compound as a prostate imaging agent.

Animals↗

PubMed1989

Myocardial kinetics of fluorine-18 misonidazole: a marker of hypoxic myocardium.

Fluoromisonidazole, a member of a class of compounds referred to as "hypoxic sensitizers," accumulates in hypoxic, viable tumor cells. We hypothesized that it might therefore accumulate also in ischemic, but non-necrotic myocardium potentially salvageable by interventional therapy. To evaluate the myocardial kinetics of [18F]fluoromisonidazole (FM), 20 isolated perfused rabbit hearts were used to characterize the uptake and binding of tracer under control conditions (n = 6), or with ischemia (flow 10% of control, n = 5), hypoxia without low flow (control flow rates with hypoxic medium, n = 5), or with reperfusion (n = 4). Myocardial retention of tracer detected externally with gamma scintillation probes after 20 min of constant [18F]FM infusion followed by 20 min of washout with nonradioactive buffer was 41 +/- 7% and 46 +/- 8% of peak activity in hearts subjected to ischemia or hypoxia, respectively, and significantly higher than in hearts subjected to either control perfusion or to ischemia followed by reperfusion (18 +/- 6 and 16 +/- 5% of peak activity, respectively, p less than 0.01). The biologic half-time of retained tracer was 40 hr in all hearts indicating essentially irreversible binding. Based on these findings, we measured uptake of [18F]FM using positron emission tomography in five dogs subjected to acute coronary occlusion. Five to thirteen millicuries of tracer were injected within 3 hr of occlusion. Within 30 min after administration of tracer, 18F accumulation in ischemic myocardium was greater than that observed in normal myocardium. The results indicate that [18F]FM accumulates in ischemic myocardium in relation to diminished tissue oxygen content and not simply because of diminished flow. Thus, this class of compounds may be potentially useful to help identify hypoxic myocardium.

Animals↗

PubMed1988

No-carrier-added radiobromination via cuprous chloride-assisted nucleophilic aromatic bromodeiodination.

Cuprous chloride-assisted aromatic bromodeiodination was investigated as a regioselective no-carrier-added labelling technique. Using 77Br-, CuCl and simple iodinated aromatic substrates in DMSO, radiochemical yields ranged from 60 to 90% after 30 min at 135 degrees C. The methodology described here holds potential for the convenient labelling of radiopharmaceuticals with 75Br, 76Br or 77Br.

Bromine Radioisotopes↗

PubMed1986

Flow cytometric determination of basophils in whole blood with n-propyl Astra Blue iodide.

Within the past year, it has become apparent, in connection with its use on automatic flow cytometers, that the quality of commercially available Alcian Blue has significantly declined. A homologous series of alkylated (C1-C7) Astra Blue quaternary ammonium halides was prepared, characterized, and evaluated for the detection of basophils in whole blood. On the Technicon H6000 flow cytometer, the resolution of the basophil cluster from the main population of unstained white blood cells was found to depend on the chain length of the quaternizing alkyl group. Optimal basophil resolution was observed for the n-propyl derivative. Correlation of the new method vs Alcian Blue as the reference on the H6000 was expressed as follows: %Baso (Astra Blue) = 0.89% Baso (Alcian Blue) + 0.12% for 180 fresh whole blood samples. Within-run precision at a basophil differential count of 0.73% was characterized by SD = 0.11, identical to that obtained for Alcian Blue. Aqueous solutions of n-propyl Astra Blue iodide, in contrast to Alcian Blue, are thermally stable. Heating the reagent for 1 h at 100 degrees C did not alter solubility or cytochemical behavior. In contrast, parallel treatment of Alcian Blue yielded insoluble material by hydrolysis of the isothiouronium groups. The reagent for basophil detection comprises n-propyl Astra Blue iodide, lanthanum chloride, sodium chloride, Tween 20, and cetylpyridinium chloride. The Astra Blue derivatives were characterized by uv-vis, ir, percentage halide, paper chromatography, and 13C NMR.

Alkylation↗

PubMed1986

2-[18F]fluoroputrescine: preparation, biodistribution, and mechanism of defluorination.

A new radiolabeled analog of putrescine, 18F labeled 2-fluoroputrescine, has been prepared as a potential in vivo imaging agent for prostate and prostate derived tumors. The radiosynthesis yielded 1.5-4.5 mCi amounts of the 18F labeled putrescine analog (1-3% yields at end-of-synthesis), with specific activities ranging from 0.85-4.3 Ci/mmol, in a synthesis time of 2 h. The in vivo biodistribution in mature male rats showed considerable uptake by the bone, indicating defluorination of the compound. In animals pretreated with aminoguanidine, an inhibitor of diamine oxidase, the enzyme important in the metabolism of putrescine, defluorination was markedly reduced, but uptake by the prostate did not improve. These results suggest the need for development of a 18F labeled analog of putrescine which does not defluorinate in vivo, and which has biological properties similar to putrescine.

Animals↗

PubMed1980

Pyridones as potential antitumor agents II: 4-Pyridones and bioisosteres of 3-acetoxy-2-pyridone.

Pyridone structural requirements for activity against murine P-388 leukemia have been extended to isosteric analogs of 3-hydroxy-4-pyridone, a compound previously found to have activity. An amino group can be substituted for the 3-hydroxyl function with retention of activity. A sulfur, but not an amino function, can replace the lactam oxygen in the 2-position. Relocation of the lactam oxygen from the 2- to the 4-position in the pyridine ring also produces active pyridones, including 2-methyl-3-acetoxy-4-pyridone. This compound, which has a T/C value of 179%, is the most active material discovered thus far in the pyridone studies.

Animals↗

PubMed1979

Pyridones as potential antitumor agents.

Based on the finding that 3-acetoxy-2-pyridone had reproducible activity against murine P-388 lymphocytic leukemia, derivatives in this series were synthesized and evaluated to determine structural parameters important for activity. Of the 32 compounds tested, 10 were active. At least two oxygen-containing functional groups are required for P-388 activity, and the 2,3-isomeric arrangement provides the greatest activity. Carbamate or acyloxy groups in the 3-position produced the most active 2-pyridones.

Animals↗

PubMedDate not supplied

Synthesis and characterization of digoxin-phospholipid conjugates.

The preparation of immunoreactive derivatives of digoxin for analytical applications is most often carried out by periodate cleavage of the terminal sugar ring (digitoxose) followed by reaction with an enzyme, protein, carrier, or related biological molecules. Here we report an improved and more efficient synthesis which was developed to provide digoxin-phospholipid conjugates useful for liposome immunoassay. The approach used involved the linking of the cleaved digitoxose through a carboxymethyl oxime functionality, which provides much improved yields of readily purified products. The synthetic modification should be applicable to the preparation of analogous phospholipid conjugates involving linkage through a sugar ring (digitoxin, ouabain, and related cardiac glycosides) or to those involving steroids (i.e., 3-digoxigenone) which can be modified to form oxime derivatives remote from key functionalities important for immunorecognition by specific antibody. The characterization of the digoxin-phospholipid conjugates with high-resolution NMR and fast atom bombardment mass spectrophotometry will also be discussed.

Chemical Phenomena↗