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Biomedical subjects

E E Kim

Publications and source records attributed to E E Kim.

At least 73 records · Page 4Linked to original sources
PubMed1994

Imaging, biodistribution and therapy potential of halogenated tamoxifen analogues.

Tamoxifen binds to estrogen receptors (ERs) and prevents breast cancer cell proliferation. This study is aimed at developing a ligand for imaging ER (+) breast tumors by positron emission tomography (PET) or single photon emission computed tomography (SPECT). [18F]-Labeled tamoxifen analogue ([18F]FTX) was prepared in 30-40% yield and [131I]-labeled tamoxifen analogue ([131I]ITX) was prepared in 20-25% yield. In mammary tumor-bearing rats, the biodistribution of [18F]FTX at 2 h showed a tumor uptake value (% injected dose/gram tissue) of 0.41 +/- 0.07; when rats were pretreated with diethylstilbestrol (DES), the value changed to 0.24 +/- 0.017. [131I]ITX at 6 h showed a tumor uptake value of 0.26 +/- 0.166; when rats were pretreated with DES, the value changed to 0.22 +/- 0.044. Priming tumor-bearing rats with estradiol, a tumor uptake value for [131I]ITX was increased to 0.48 +/- 0.107 at 6 h. In the [3H]estradiol receptor assay, tumors had a mean estrogen receptor density of 7.5 fmol/mg of protein. In gamma scintigraphic imaging studies with [131I]ITX, the rabbit uterus uptake can be blocked by pretreatment with DES. Both iodo-tamoxifen and tamoxifen reduced ER(+) breast tumor growth at the dose of 50 micrograms in tumor-bearing mice. The findings indicate that tamoxifen analogue uptake in tumors occurs via an ER-mediated process. Both analogues should have potential for diagnosing functioning ER(+) breast cancer.

Animals↗
PubMed1993

Positron emission tomography with fluorine-18-deoxyglucose in the detection and staging of breast cancer.

BACKGROUND: An increasing number of patients with breast cancer is being treated with preoperative chemotherapy. Evaluation of treatment response may be facilitated by positron emission tomography (PET) with 18F-fluoro-2-deoxy-D-glucose (FDG). This noninvasive technique may allow prediction of the chemotherapy outcome in an early phase of the treatment. METHODS: Prerequisites for treatment monitoring with PET are good FDG uptake in the tumor, high specificity, and a reliable quantification technique. These factors were studied in 20 patients with primary breast cancer, lymph node metastases, benign breast lesions, a combination of these abnormalities, or no abnormality. RESULTS: In 10 of 11 patients with primary breast cancer, the tumor was visualized. The median tumor-to-normal-tissue-uptake ratio was 4.9. In all five patients with increased uptake in the lymph node basin, pathologic proof of metastatic cancer was found. Of the patients with benign or no disease of the breast, slightly increased uptake was seen in one patient with fibrocystic disease. CONCLUSION: It is concluded that PET with FDG can be used for breast cancer imaging and staging.

Adenocarcinoma↗
PubMed1993

Evolutionary divergence of pobA, the structural gene encoding p-hydroxybenzoate hydroxylase in an Acinetobacter calcoaceticus strain well-suited for genetic analysis.

The pobA gene encoding p-hydroxybenzoate hydroxylase (PobA) from Acinetobacter calcoaceticus has been developed as a genetic tool for the analysis of structure-function relationships in this enzyme. By exploiting the favorable genetic system of A. calcoaceticus strain ADP1, it is possible both to select and to map mutations which disturb PobA activity; characterization and sequence determination of mutants derived in this manner may complement site-directed studies with the homologous Pseudomonas aeruginosa gene. We have determined the nucleotide (nt) sequence of A. calcoaceticus pobA and performed a systematic comparison of the deduced amino acid (aa) sequence with that of the PobA enzyme from Pseudomonas fluorescens, for which the three-dimensional structure is known. Despite a 26% difference in the G+C content of the homologous genes, constraints against structural divergence of the proteins were revealed by an overall identity of 62.4% in the aligned aa sequences of PobA. Clusters of identical sequence occur at previously identified sites of ligand binding and at regions associated with subunit-subunit interaction. Based on the conservation of specific residues involved in flavin binding, we have assembled a consensus sequence for nicotinamide-flavoprotein monooxygenases which differs from that of the oxidoreductase class of flavoproteins. In addition to the conserved regions shared by the two PobA homologs, there are isolated pockets of divergence. The nt sequence divergence in one such region within the A. calcoaceticus gene can be attributed to the acquisition of short nt sequence repetitions.

4-Hydroxybenzoate-3-Monooxygenase↗
PubMed1993

Use of [18F]fluorodeoxyglucose positron emission tomography in patients with primary malignant brain tumors.

In patients with malignant gliomas, [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) may discriminate tumor progression from radionecrosis. We evaluated data from 50 patients undergoing FDG-PET for suspicion of tumor progression. Forty-nine were treated with surgery, 48 with radiotherapy, and 37 with chemotherapy. Twenty-one had intensive radiotherapy with either three daily treatments in two 5-day periods and intravenous carboplatin (17) or interstitial brachytherapy or stereotactic radiotherapy. Twenty underwent surgery after magnetic resonance imaging/FDG-PET; 9 demonstrated increased uptake of FDG and evidence of tumor, whereas 6 had decreased uptake and no evidence of tumor. In 5 patients, there was no correlation (all had intensive radiotherapy). In 17 patients who received bromodeoxyuridine intravenously just before surgery, the bromodeoxyuridine labeling index corresponded to the histological appearance in all but 2 patients (both had received intensive radiotherapy). In 30 patients without surgery, decreased uptake of FDG suggested prolonged survival; increased uptake of FDG did not predict survival. Eight of 10 with intensive radiotherapy had decreased label uptake. We conclude FDG-PET for evaluation of patients with possible recurrent tumors requires more study. In patients with intensive radiotherapy, FDG-PET results cannot be correlated accurately with tumor progression.

Adult↗
PubMed1993

Imaging of colorectal carcinoma with technetium-99m radiolabeled Fab' fragments.

In this phase III study, patients who had previously undergone surgery for colorectal cancer were studied using a technetium-99m (99mTc)-labeled anti CEA antibody (IMMU-4 [Immunomedics, Morris Plains, NJ] 1mg of protein) to evaluate recurrence. Total-body, planar, and single photon emission computed tomography (SPECT) images were performed within 6 hours of injection. Objectives were to evaluate the efficacy of the 99mTc-labeled anti-CEA antibody, to assess sensitivity and specificity of the agent in known lesions, and to detect occult disease. The impact of antibody study on subsequent surgery was also evaluated. The Fab' fragment has a molecular weight of 54,000 and is supplied as a lyophilized kit that can be instantaneously labeled with 20 to 30 mCi of [99mTc]pertechnetate. In 9 patients with known disease, planar spot imaging identified lesions in 7 (78% sensitivity), SPECT imaging detected lesions in 8 (88% sensitivity), and 1 patient did not have SPECT. In the group of 10 patients with occult (or equivocal) disease, planar imaging sensitivity was 50%, and SPECT sensitivity was 100%. Analysis by site showed 14 of 24 lesions detected by planar imaging (58% sensitivity), and SPECT detected 24 of 24 lesions (100% sensitivity). Tumors as small as .5 cm were visualized in the 19 patients studied. The surgeon judged the antibody study to be impact neutral in 73% of the cases and helpful in 27% of the cases when antibody study altered the presurgical plan.

Colorectal Neoplasms↗
PubMed1993

Extraosseous multiple myeloma: imaging features.

Multiple myeloma is a disseminated malignant neoplasm usually derived from a single clone of plasma cells. Patients with myeloma have diverse signs such as anemia, hypercalcemia, uremia, pathologic fractures, and recurrent infections. Extraosseous manifestations are found in less than 5% of patients with multiple myeloma. They can arise in any tissue, and their presence has been associated with more aggressive disease. The purpose of this essay is to illustrate the imaging findings of extraosseous myeloma and heighten awareness of this unusual manifestation of multiple myeloma.

Adult↗
PubMed1993

Synthesis of [18F]fluoroalanine and [18F]fluorotamoxifen for imaging breast tumors.

To develop ligands for imaging breast tumors, [18F]fluoro analogue of tamoxifen and [18F]fluoroalanine were radiosynthesized. In vivo biodistribution studies were performed in mammary tumor-bearing rats. In studies on the biodistribution of an [18F]fluoro analogue of tamoxifen, tumor uptake decreased when rats were pretreated with diethylstilbestrol (DES), suggesting that tracer uptake in tumors was receptor-mediated. An estrogen receptor assay indicated that tumors have a receptor density of 7.5 fmol/mg protein. Studies of the distribution of [18F]fluoroalanine in tissue showed that the tumor-to-tissue ratio increases as a function of time. Positron emission tomography (PET) images of tumor-bearing rats demonstrated that tumors can be visualized 1 h after rats are injected with an [18F]fluoro analogue of tamoxifen. PET imaging of pigs after injection of 10 mCi of [18F]fluoro analogue of tamoxifen showed uterine uptake that could be blocked by DES (50 mg). The findings suggest that both radiotracers are useful for imaging breast tumors.

Alanine↗
PubMed1993

Nuclear hepatobiliary imaging.

Recent improvements in hepatobiliary radiopharmaceuticals and the high prevalence of biliary tract disease have resulted in a larger role for hepatobiliary imaging in clinical applications. The use of hepatobiliary imaging in assessing hepatic blood flow, hepatocyte function, biliary drainage, and complications in patients with jaundice or abdominal pain or surgery, as well as its primary use in diagnosing acute cholecystitis, is discussed.

Bile Duct Diseases↗
PubMed1992

Refinement of the crystal structure of ribonuclease S. Comparison with and between the various ribonuclease A structures.

Ribonuclease S (RNase-S) is a complex that consists of two proteolytic fragments of bovine pancreatic ribonuclease A (RNase-A): the S-peptide (residues 1-20) and S-protein (residues 21-124). We have refined the crystal structures of three RNase-S complexes. The first two contain the full-length 20-residue S-peptide and were studied at pHs of 4.75 and 5.5. The third one consists of a truncated form of S-peptide (residues 1-15) and was studied at pH 4.75 as the reference structure for a series of mutant peptide complexes to be reported separately. Excluding residues 16-23 which are either missing (in the S15 complex) or disordered (in both S20 complexes), all three structures refined at 1.6-A resolution are identical within the estimated errors in the coordinates (0.048 A for the backbone atoms). The R-values, residual error, range from 17.4% to 18.6%. The final model of S20, pH 4.75, includes 1 sulfate and 84 water molecules. The side chains of 11 residues were modeled in two discrete conformations. The final structures were independent of the particular RNase-A or RNase-S used as a starting model. An extensive comparison with refined crystal structures of RNase-A reveals that the core of the molecule which is held together with extensive hydrogen bonds is in identical pattern in all cases. However, the loop regions vary from one structure to another and are often characterized by high B-factors. The pattern of thermal parameters appears to be dependent on crystal packing and correlates well with the accessibility calculated in the crystal. Gln60 is a conserved residue in all sequences known to date for this class of ribonucleases. However, it is the only residue that is clearly defined in an unfavorable position (phi = -100 degrees, psi = -130 degrees) on the Ramachandran plot. The origin of the substantial differences between RNase-A and RNase-S in stability to both acid and temperature denaturation and in susceptibility to proteolysis at neutral pH is not obvious in our visual comparison of these two structures.

Animals↗
PubMed1992

Evaluation of sensitivity and specificity of upper extremity radionuclide venography in cancer patients with indwelling central venous catheters.

Two hundred twenty upper extremity radionuclide venograms were performed using upper extremity injection of 5 mCi of Tc-99m DTPA in each arm of patients with indwelling central lines. Evidence of obstruction was found in 123 patients, collateral flow without anatomic obstruction in six patients, and a slow-flow pattern in 12 patients. Twenty-six of these also underwent upper extremity contrast venography within 48 hours of the scan. Contrast venograms and radionuclide venograms agreed in 19 patients (16 correctly identified as obstructed, three correctly identified as unobstructed). Six patients showed the slow-flow pattern without collaterals or obstruction. Subsequently, six follow-up contrast studies showed no evidence of obstruction or collaterals. The authors conclude that obstruction with collateral flow on radionuclide venograms correctly predicts obstruction. However, the slow-flow pattern does not and should not be used as the sole criterion to diagnose partial obstruction.

Arm↗
PubMed1992

Differentiation of residual or recurrent tumors from post-treatment changes with F-18 FDG PET.

Positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose (FDG) was used to differentiate recurrent or residual malignant disease from the effects of cancer treatment. Transaxial images were obtained after injection of 5-10 mCi (185-370 MBq) of F-18 FDG in 68 patients (including 33 with brain tumors) whose posttreatment computed tomographic (CT) or magnetic resonance (MR) imaging findings had been suggestive of malignant disease. PET findings were correlated with surgical results in 18 patients and with the outcomes of CT, MR imaging, clinical, and laboratory 9-month follow-up studies in 50 patients. There was good agreement between F-18 FDG uptake and presence or absence of malignant disease except in four cases of brain tumors in which histologic findings could not be correlated with biologic behavior. The putative sensitivity and specificity in the 33 cases of brain tumors were 80% and 94%, respectively. The authors conclude that PET with F-18 FDG is useful in detection of previously treated metabolically active tumors but is limited in diagnosis of recurrent microscopic or metabolically inactive tumors.

Abdominal Neoplasms↗
PubMed1992

SPECT in the evaluation of cancer patients: not quo vadis; rather, ibi fere summus.

In the past 7 years, single photon emission computed tomography (SPECT) has evolved from an interesting nuclear medicine technique rarely performed because of technical difficulties into a valuable clinical tool in the management of cancer cases. The development of stable multidetector instruments with collimators and gantries specifically designed for SPECT and the introduction of new radiopharmaceuticals recently approved by the U.S. Food and Drug Administration have rapidly moved SPECT from the field of clinical investigation to clinical practice. SPECT is a valuable addition to other tomographic modalities capable of displaying the physiology of disease as well as anatomy. In this work the authors describe the role of SPECT in a cancer center and, in particular, how they use it to solve clinical problems. They also review the published literature, when appropriate. The authors have found SPECT of particular value in evaluation of myocardial ischemia, in differentiating tumor recurrence from posttherapy changes in the lymphomas, in tumor diagnosis and surveillance, and in separating hemangioma from malignant lesions in the liver.

Abdomen↗
PubMed1992

Multiple myeloma: spinal MR imaging in patients with untreated newly diagnosed disease.

Spinal magnetic resonance (MR) imaging was performed in 29 patients with newly diagnosed, untreated multiple myeloma. Nineteen (66%) patients were asymptomatic. Sagittal pre- and postcontrast T1-weighted spin-echo images and gradient-recalled-echo images of the thoracic and lumbosacral spine were obtained. Marrow involvement was identified in 20 (69%) patients. There were three MR patterns: focal lesions in nine patients (31%), diffuse involvement in seven (24%), and an inhomogeneous pattern of tiny lesions on a background of normal marrow in four (14%). A statistically significant correlation between MR imaging patterns of marrow involvement and serum hemoglobin values (one-way, P = .0899; Kruskal-Wallis, P = .0620) and between MR imaging patterns and percentage of marrow plasmacytosis (Kruskal-Wallis, P = .0314) was noted, with patterns of diffuse and focal marrow involvement associated with more abnormal values. Spinal MR imaging in patients with early myeloma may reveal marrow involvement in both symptomatic and asymptomatic patients. Some correlation was found between MR imaging patterns and laboratory indexes of disease.

Adult↗
PubMed1991

Mutation of a single amino acid converts germ cell alkaline phosphatase to placental alkaline phosphatase.

Human placental and germ cell alkaline phosphatases (PLAP and GCAP, respectively), are characterized by their differential sensitivities to inhibition by L-leucine, EDTA, and heat. Yet, they differ by only 7 amino acids at positions 15, 67, 68, 84, 241, 254, and 429 within their respective 484 residues. To determine the structural basis and the amino acid(s) involved in these physicochemical differences, we constructed three GCAP mutants by site-directed mutagenesis and six GCAP/PLAP chimeras and then expressed these alkaline phosphatase mutants in COS-1 cells. We report that the differential reactivity of PLAP and GCAP depends critically on a single amino acid at position 429. GCAP with Gly-429 is strongly inhibited by L-leucine, EDTA, and heat, whereas PLAP with Glu-429 is resistant. By substituting Gly-429 of GCAP with a series of amino acids, we demonstrate that the relative sensitivities of these mutants to L-leucine, EDTA, and heat inhibition are, in general, parallel. Mutants in the order of resistance to these treatments are: Glu (most resistant), Asp/Ile/Leu, Gln/Val/Lys, Ser/His, and Arg/Thr/Met/Cys/Phe/Trp/Tyr/Pro/Asn/Ala/Gly (least resistant). However, the Ser-429 and His-429 mutants were more resistant to EDTA and heat inhibition than the wild-type GCAP, but were equally sensitive to L-leucine inhibition. Structural analysis of mammalian alkaline phosphatase modeled on the refined crystal structure of Escherichia coli alkaline phosphatase indicates that the negative charge of Glu-429 of PLAP, which simultaneously stabilizes the protein as a whole and the metal binding specifically, probably acts through interactions with the metal ligand His-320 (His-331 in E. coli alkaline phosphatase). Replacement of codon 429 with Gly in GCAP leads to destabilization and loosening of the metal binding. The data suggest that the natural binding site for L-leucine may be near position 429, with the amino and carboxyl groups of L-leucine interacting with bound phosphate and His-432 (His-412 in E. coli alkaline phosphatase), respectively.

Alkaline Phosphatase↗