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Biomedical subjects

M G Woldring

Publications and source records attributed to M G Woldring.

At least 19 recordsLinked to original sources

57Co-bleomycin scintigraphy for the staging of lung cancer.

The value of Cobalt-57 bleomycin (57Co-BLM) scintigraphy in the detection of lymph node metastases in the hilum and mediastinum was investigated in 132 patients with peripherally located lung cancer. In one half of the patients with metastases, these were visualized. Specificity was 98%. These results were better than those obtained with chest radiography and conventional roentgen tomography. 57Co-BLM scintigraphy is routinely used in the staging of patients with lung cancer, obviating the need for mediastinoscopy.

Adult↗

Metabolic studies with L-[1-14C]tyrosine for the investigation of a kinetic model to measure protein synthesis rates with PET.

To evaluate a kinetic model for measuring protein synthesis rates by positron emission tomography (PET) in neoplastic and normal tissue, metabolic studies with L-[1-14C]tyrosine were carried out. As an animal model, rats bearing Walker 256 carcinosarcoma were used. Within 60 min after injection, several metabolic parameters were measured. The highest radioactivity uptake, expressed as the differential absorption ratio, was found in pancreas, followed by liver, tumor, and brain. A rapid decarboxylation was observed during the first 15 min. After 60 min, 7.4% of the total injected 14C was expired as 14CO2. In plasma a significant amount of [14C]bicarbonate was detected, but in tissue the amount was negligible. Protein incorporation increased with time. The incorporation rate was the highest in the liver followed by pancreas, tumor, and brain tissues. At 60 min after injection, more than approximately 80% of the 14C in tissue was protein bound. In plasma after a rapid clearance during the first 15 min, the total 14C level increased rapidly and paralleled the increase of protein-bound 14C. As nonprotein [14C]metabolites, in plasma, tumor and brain tissues, p-hydroxyphenylpyruvic acid, p-hydroxyphenyllactic acid, and unidentified metabolites were observed by high performance liquid chromatography. The formation of 14C-labeled 3,4-dihydroxyphenylalanine was found to be negligible. The total amount of these nonprotein metabolites increased with time. At 60 min after injection the percentages of the total nonprotein metabolites and [14C]bicarbonate were only 5.0%, 1.9%, and 3.7% in plasma, tumor and brain tissue, respectively. From our data it is concluded that [11C]carboxylic-labeled tyrosine would be a suitable radiopharmaceutical for measuring protein synthesis rates in neoplastic and normal tissue by PET.

Animals↗

Comparison of L-[1-11C]methionine and L-methyl-[11C]methionine for measuring in vivo protein synthesis rates with PET.

To evaluate the feasibility of using either L-[1-11C]-methionine or L-[methyl-11C]methionine for measuring protein synthesis rates by positron emission tomography (PET) in normal and neoplastic tissues, distribution and metabolic studies with 14C- and 11C-labeled methionines were carried out in rats bearing Walker 256 carcinosarcoma. The tissue distributions of the two 14C-labeled methionines were similar except for liver tissue. Similar distribution patterns were observed in vivo by PET using 11C-labeled methionines. The highest 14C incorporation rate into the protein-bound fraction was found in the liver followed by tumor, brain, and pancreas. The incorporation rates in liver and pancreas were different for the two methionines. By chloroform-methanol fractionation of these four tissues, in liver significantly different amounts of 14C were observed in macromolecules. Also in brain tissue slight differences were found. By HPLC analyses of the protein-free fractions of plasma, tumor, and brain tissue at 60 min after injection, for both methionines several 14C-labeled metabolites in different amounts, were detected. About half of the 14C-labeled material in the protein-free fraction was found to be methionine. In these three tissues the amount of nonprotein metabolites and [14C]bicarbonate amount ranged from 10% to 17% and 12% to 15% for L-[1-14C]methionine and L-[methyl-14C]methionine, respectively. From these results it can be concluded that the minor metabolic pathways have to be investigated in order to quantitatively model the protein synthesis by PET.

Animals↗

Carbon-11 labelled tyrosine to study tumor metabolism by positron emission tomography (PET).

To measure the rate of protein synthesis in human neoplasms by positron emission tomography, we prepared no carrier added DL-(1-11C)-tyrosine by 11C-carboxylation of the appropriate alpha-lithioisocyanide followed by hydrolysis of the isocyanide function and removal of the protecting methoxy group. The purification, resolution and solvent switch to saline was performed by high performance liquid chromatography (HPLC). DL-(1-11C)-Tyrosine in 0.1 N NaH2PO4 buffer was prepared with a radiochemical yield of 8%-16% (EOS, 35 min). The enantiomeric separation and solvent switch to saline were achieved in 5 min and 10 min respectively. Consequently L-(1-11C)-tyrosine in physiological saline was obtained in 2%-4% radiochemical yield. Tumor accumulation in rats with the experimental WALKER 256 carcinosarcoma was observed for both the L- and D-isomer. Using positron emission tomography a tumor/muscle ratio of two was observed for the L-isomer 15 min after injection. The corresponding figure for the D-isomer was 2.5. The first clinical results with DL-(1-11C)-tyrosine show accumulation of radioactivity in meningioma, a primary breast carcinoma and in liver metastases of a colonic carcinoma.

Animals↗

Synthesis of carbon-11 labelled glycine and the dipeptides L-phenylalanylglycine and L-leucylglycine.

Carbon-11 labelled glycine has been prepared in 30 min by carboxylation of alpha-lithiomethylisocyanide with a radiochemical yield of 10-15%. After coupling with L-phenylalanine-N-carboxyanhydride and L-leucine-N-carboxyanhydride followed by HPLC purification, the corresponding dipeptides were obtained in 20 min with a radiochemical yield of 30-40%. Consequently, starting with 11CO2, non carrier added L-phenylalanyl[1-(11)C]glycine and L-leucyl-[1-(11)C]glycine in 0.1 N NaH2PO4 were obtained in 50 min with a radiochemical yield of 3-6%. The radiochemical yield figures are not corrected for decay.

Carbon Isotopes↗

A comparison of the sensitivity of PET and NMR for in vivo quantitative metabolic imaging.

Using positron emission tomography (PET) in combination with compounds labelled with positron-emitting radionuclides like 11C, 13N and 15O, it is possible to study metabolism in vivo in a non-invasive way. Nuclear magnetic resonance (NMR) imaging takes advantage of the spin of protons in water molecules to measure both their number and relaxation times in vivo, but is, in principle, not limited to protons and can also be used for other nuclei with a non-zero spin, e.g. 13C and 31P. The use of 13C opens the possibility of studying the metabolism of a large number of compounds. In order to choose the appropriate methodology for metabolic imaging, i.e. PET or NMR, it is important to know the sensitivity of each modality. The present study outlines the sensitivity of both techniques.

Carbon Isotopes↗

Spermidine level as a parameter in the treatment of patients with malignant melanoma.

Before, during, and after 19 courses of chemotherapy given to patients with disseminated malignant melanoma plasma spermidine levels were determined with a radioimmunoassay. Baseline values were normal in 17 courses, a doubling of plasma levels following chemotherapy occurred in 13 courses. There was no relation between the occurrence of a tumor response and an increase in spermidine levels nor between hematological toxicity or digestive tract toxicity and spermidine levels.

Adult↗

Syntheses of carbon-11 labelled ornithine and lysine. Preliminary accumulation studies in rats with Walker 256 carcinosarcoma.

DL-[1-11C]ornithine and lysine have been synthesized by carboxylation of the corresponding alpha-lithioisocyanide with a radiochemical yield of up to 14% without correction for decay. The total preparation time is 50 min. Accumulation of both DL-[1-11C]ornithine and lysine in Walker 256 carcinosarcoma is observed, with a tumor/non-tumor ratio of 4.9 and 4.5 respectively, at 45 min after intravenous injection.

Animals↗

The preparation of carbon-11 labelled proline for positron emission tomography. Preliminary distribution studies in rats with Walker 256 carcinosarcoma.

DL-[1-11C]Proline has been synthesized by carboxylation of alpha-lithiopyrrolidyl-N-tert-butyl-formamidine with a radiochemical yield of up to 18% without correction for decay. The total synthesis time is 45 min. Accumulation of DL-[1-11C]proline has been shown in Walker 256 carcinosarcoma transplanted in rats. A tumor/non-tumor ratio of 5.9 was found at 45 min after i.v. injection.

Animals↗

A rotating double-headed positron camera.

Based on a double-headed rotating uncollimated scintillation camera system, a positron imaging device was developed. After a rotating data acquisition in coincidence mode, 16 transverse section images are reconstructed by back projection. To obtain a uniform response, a limited angle reconstruction option is incorporated in this process. After correction for the system response by a three-dimensional deconvolution technique, the 16 transverse section images are stored on disk as a standard patient study for further analysis. The system can also be operated in a stationary mode. In this mode longitudinal tomographic images are obtained. Return to single photon scintigraphy is possible by remounting the collimators and by switching off the coincidence electronics.

Brain↗

Scintigraphy with 57Co-bleomycin in the detection of lung cancer. A review of 268 well-documented patients.

Over a 5-year period 57Co-bleomycin scintigraphy for tumor detection was performed with a large-field-of-view gamma camera. The scintigrams of 268 patients with lung cancer, with a benign lesion, or with no abnormality in the chest, were reviewed. A sensitivity of 96% was found. In a group of 193 patients in whom a preoperative pathologic diagnosis could not be obtained sensitivity was 95%, specificity was 87%. Correlation between tumor size and tumor-to-non-tumor ratio was established for squamous cell carcinoma, adenocarcinoma, and small cell anaplastic carcinoma. Adenocarcinomas were smaller and showed lower tumor-to-non-tumor ratios than other histologic types. In squamous cell carcinoma a possible correlation between tumor-to-non-tumor ratio and histologic differentiation was investigated, but could not be established. It is concluded that 57Co-bleomycin scintigraphy is helpful in the evaluation of patients with possible lung cancer in whom a preoperative pathologic diagnosis cannot be obtained.

Adenocarcinoma↗

Nitrogen-13 and xenon-133 ventilation studies.

Due to the solubility of xenon-133 in blood and tissues, errors are introduced in the determination of regional pulmonary ventilation. We investigated these errors by comparing the results from ventilation measurements with Xe-133 and N-13 in five normal subjects (both at rest and during exercise) and in seven patients after a pneumonectomy. In the normal subjects at rest, the upper lung fields showed no significant difference in the uptake rates of the two gases. In the middle and lower lung fields, however, the uptake rate for Xe-133 was higher than for N-13. During exercise a significant increase of the specific ventilation was found in the upper lung fields for N-13 compared with Xe-133. In the pneumonectomy patients the overall uptake rate for Xe-133 in the intact hemithorax was 25% larger than for N-13. Over the pneumonectomized hemithorax the uptake of the fastest component of Xe-133 was (8.5 +/- 1.3)% of the total. The total chest-wall contribution of Xe-133 was (27 +/- 8)% of the total count rate.

Adult↗

The significance of the aminoterminal propeptide of type III procollagen in paroxysmal nocturnal haemoglobinuria and myelofibrosis.

The level of the aminoterminal propeptide Col 1-3 of type III procollagen (PC-III) was determined in patients with paroxysmal nocturnal haemoglobinuria (PNH) and primary myelofibrosis (PMF), to study whether PC-III can be used as a parameter for the rate and/or degree of bone marrow replacement with collagen. Normal PC-III levels were found in PNH (6.6 +/- 1.1 micrograms/l; N: 8.6 +/- 1.8 micrograms/l), while significantly increased levels were found in PMF (24.8 +/- 2.2 micrograms/l). During a follow-up of 1 year, a slight increase of 2 micrograms/l occurred in three patients with a stable fibrosis, while one patient with more active disease demonstrated an increase of 25 micrograms/l. Treatment with acetylsalicylic acid led to a decline of PC-III as well as beta-thromboglobulin level, although normalization did not occur. It was demonstrated by means of gel filtration that the antigens related to the PC-III peptide were heterogenous, and that in PMF at least two main peaks were present, with molecular masses equal to and smaller than PC-III peptide. These data demonstrate that the radioimmunoassay cannot be used for the quantitative determination of PC-III; nevertheless it gives some insight in the process of bone marrow fibrosis.

Aged↗

Synthesis of no-carrier-added L- and D-[1-11C]-DOPA.

No-carrier-added DL-[1-11C]-DOPA has been synthesized by carboxylation of an alpha-lithioisocyanide with a radiochemical yield of up to 15% without correction for decay. The total synthesis time is 30 min. The resolution of the D- and L-isomers was accomplished within 16 min by HPLC using a chiral stationary phase and a phosphate buffer of pH 4.5 as eluent.

Brain↗

57Co-bleomycin and 67Ga-citrate in detecting and staging lung cancer.

In the investigation of suspected lung cancer bleomycin labelled with cobalt-57 and gallium-67 labelled with citrate are currently used to detect the primary tumour and to establish the presence of metastases in the lung hilum and mediastinum. A comparative study of these radio-pharmaceuticals was performed in 63 patients with proved lung cancer. 57Co-bleomycin showed the primary tumour in 58 patients (92%) and 67 Ga-citrate in 34 (54%) (p less than 0.01). The average tumour-to-lung ratio was 3.4 with 57Co-bleomycin and 1.5 with 67Ga-citrate. Proved metastases in the hilum or the mediastinum were visualised with 57Co-bleomycin scintigraphy in 16 out of 18 patients (89%) and with 67 Ga-citrate scintigraphy in only eight (45%) (p less than 0.01). These results indicate that 57Co-bleomycin scintigraphy is more suitable for detecting and staging lung cancer than is 67Ga-citrate. 57Co-bleomycin is valuable in the detection of peripheral lesions, in which a pathological diagnosis is difficult to achieve, since a positive scintigram indicates malignancy. When 57Co-bleomycin scintigraphy suggests hilar or mediastinal metastases mediastinoscopy should be carried out; but when no metastases are apparent it is reasonable to proceed directly to thoracotomy without mediastinoscopy.

Adult↗

Estrogen receptor binding radiopharmaceuticals: II. Tissue distribution of 17 alpha-methylestradiol in normal and tumor-bearing rats.

Tritiated 17 alpha-methylestradiol was synthesized to investigate the potential of the carbon-11-labeled analog as an estrogen-receptor-binding radiopharmaceutical. In vitro, 17 alpha-methylestradiol is bound with high affinity to the cytoplasmic estrogen receptor from rabbit uterus (Kd = 1.96 x 10(-10)M), and it sediments as an 8S hormone-receptor complex in sucrose gradients. The compound shows specific uptake in the uterus of the adult rat, within 1 hr after injection. After 30 min the uterine uptake was 1.73% dose/g. In female rats bearing DMBA-induced tumors, specific uterine and tumor uptakes were observed, although at 30 min the tumor uptake was only 23-30% of the uptake in the uterus. Tritiated 17 alpha-methylestradiol with a specific activity of 6 Ci/mmole showed a similar tissue distribution. Our results indicate that 17 alpha-methylestradiol is promising as an estrogen-receptor-binding radiopharmaceutical.

9,10-Dimethyl-1,2-benzanthracene↗

Detection of lung cancer with 55Co-bleomycin using a positron camera. A comparison with 57Co-bleomycin and 55Co-bleomycin single photon scintigraphy.

57-Co-bleomycin is useful in the detection and staging of lung cancer, but the long half-life of 57Co (270 days) has discouraged its widespread acceptance. We investigated the shorter living positron emitting 55Co (half-life 18.2 h) as a level for bleomycin. In eleven patients with proven lung cancer scintigraphy with 55Co-bleomycin, using a positron camera, demonstrated the tumor in ten cases. Tumor to lung ratios were calculated. The results were superior to those obtained with 55Co-bleomycin single photon imaging but inferior to those obtained with 57Co-bleomycin scintigraphy.

Aged↗