Search

Resumen y conclusiones Como resultado de nuestra experiencia en la determinacion de la perfusion regional del pulmon con xenon-133 durante la respiracion espontanea, hemos visto que algunos de los errores del metodo obedecen a una causa tecnica que puede ser eliminada mas o menos facilmente. Otros por el contrario dependen del mismo paciente y si bien no pueden eliminarse, deberan tenerse en cuenta al interpretar los resultados. Ya que los errores tecnicos dependen del aparataje empleado, cada laboratorio debera hallar experimentalmente las correcciones necesarias en su caso particular.

The rise-time method as a position sensitive read-out of a proportional chamber is investigated. An expression is derived for the pulse form at the end of the wire as a function of time and position of the discharge. With a proper termination the response of the line can be made linear. From the pulse form the zero-cross time, linearity and sensitivity are calculated. The calculations were experimentally verified with a 30 cm long resistive wire detector. An expression for the noise is derived and the influence of the filter time constants on the resolution is discussed.

Carbon-11 labelled methyllithium was prepared from 11 C-methyl-iodide by halogen-metal interconversion with n-butyllithium. Within 10 min the exchange was nearly quantitative. The methyl donating properties of this high specific active 11 C-precursor were demonstrated by the addition to 17-keto steroids. 11 C-labelled 17α-methylestradiol, 17α-methyltestosterone and 17α-methylestradiol 3-methylether with specific activities of 1−5 Ci/mmol were prepared.

Over a 5-year period /sup 57/Co-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 /sup 57/Co-bleomycin scintigraphy is helpful in the evaluation of patients with possible lung cancer in whom a preoperative pathologic diagnosis cannot be obtained.

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.

Preparation of a number of cyclotron produced short lived radiopharmaceuticals labelled with11C,18F,13N,123I and81Rb/81Kr are described.

An electromagnetic valve for use in exercise rebreathing studies is described. This valve enables the investigator to connect a rebreathing system immediately after the onset of inspiration even at high breathing frequencies. The rapid switching causes minimal leakage; the rebreathing bag can be washed out and refilled without disconnection during exercise testing. For one year this valve has been used in measurements of functional residual capacity and diffusing capacity during exercise in volunteers as well as in patients.

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.

The performance parameters of a positron camera consisting of two uncollimated scintillation cameras operated in a coincidence mode, are discussed. The image of the positron emitting radionuclide distribution is constructed by back-projection. On-line one focal plane can be constructed in hardware. By storing the four position signals corresponding to the coincident photo-events on disk a deferred selection of multiple focal planes is possible. The spatial resolution of the system is 5.5 mm fwhm. The temporal resolution varies, depending on the single count rates, between 6.5 ns and 10 ns fwhm. The sensitivity of the system is 200 Hz/μ Ci for a point source in the geometrical center of the system at a detector separation of 50 cm. The maximum coincidence count rate is 7.5 kHz.

The cerebral distribution of the positron-emitting agent [1- 11 C]β-(3,4-dihydroxyphenyl) - d,l -α-alanine ([ 11 C]DOPA) was studied after intravenous injection in rats pretreated with the peripheral decar☐ylase inhibitor, carbidopa. Within 15 min of injection the accumulation of carbon-11 was almost twice as high in cortical areas and cerebellum as in the striatum and the brain stem. After destruction of catecholamine containing nerve endings with 6-hydroxydopamine, the level of carbon-11 in the striatum was higher than in rats not treated with this neurotoxin. Pretreatment of rats with haloperidol or l -DOPA did not change the distribution pattern of carbon-11. Without pretreatment with carbidopa a uniform distribution of the label in the brain was observed. We suggest that [ 11 DOPA is a potentially useful agent external detection with positron imaging systems in patients and large animals of brain regions rich in the enzyme dopa-decar☐ylase. (EC 4. 1.1.26).

A number of metal selenides were investigated as target material for the production of 75Br by the 76Se(p,2n)75Br reaction. Ag2Se, CuAgSe, and Cu2Se met the rqquirements for an economical and fast production procedure. These selenides were found to be stable during bombardment with 1–4 μA 28 MeV protons (beam dimension 0.4 cm2) and at the dry distillation temperature of 1473 K. A target system was developed for radiobromine production with a 7 μA 28−22 MeV proton beam on Cu2Se. At EOB the calculated thick target yield is 1.59 GBq/μAh (43 mCi/μAh) and the radionuclidic purity is 98.6%. The radiobromine was separated from Cu2Se by dry distillation at 1473 K and collected for 80–95% on platinum wool pretreated with CaCl2. Radiochemical analysis showed the radiobromine to be Br− for 95% and BrO3− for 5%. The total loss of selenide after irradiation and distillation was found to be less than 0.1%.

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.

The construction and characteristics of an electromagnetic delay line are described. The materials used in the delay line are selected because of their dielectric and magnetic properties. The effective length of the delay line is 24 cm and the delay 1.4 μs. The rise time of the pulses is 70 ns. The specially designed preamplifiers, based on the principle of “electronic cooling”, and the electronic set up are discussed. The application of the dealy line as a device for position read-out of the avalanches in a proportional chamber, used for the measurement of conversion electrons in a double focusing β-spectrometer, is described.

SummaryCarbon-11 (t½ = 20.4 min, β+) labelled DL-α-phenylalanine and DL-α-phenylglycine were administered intravenously to rats and the distribution of the radioactive amino acids over pancreas, liver, spleen, kidneys and blood was measured after several time intervals. From these results the ratios of the concentration in pancreas and liver were calculated and compared with the corresponding ratios from the literature for some 18F-labelled aromatic amino acids and L-selenomethionine-75Se. On the basis of this study it appears that DL-α-phenylglycine-l-11C, in spite of a small percentage of the administered dose reaching the pancreas, and DL-α-phenylalanine-l-11C are better suited to pancreas scintigraphy than L-selenomethionine-75Se.

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.

The medical application of some short lived carrier free radionuclides (11C, 13N, 55Co, 197Hg) produced with the external beam of the KVI cyclotron are outlined. Some approaches to labelling with these nuclides are discussed. The development of a multiwire proportional counter for the imaging of low energy gamma rays is described. Images of positron emitters with a dual head Anger camera are shown.

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.

An expanding field of interest in nuclear medicine is the preparation of radiopharmaceuticals labelled with cyclorrn produced isotopes of short half life.1–3 In an investigation to prepare 11C-labelled amino acids we developed a new and repid synthesis for the preparation of a-phenylglycine. The preparation of other amino acids by this route is under investigation. α-Lithiobenzylisocyande4 was treated with carbondioxyde and the intermediate was hydrolysed to the amino acid. The overall yield (75–808) was accomplished in 50–70 minutes.+

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.

DL -[1- 11 C]Proline has been synthesized by carboxylation of α-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- 11 C]-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.

A rapid methods for preparation and purification of β-(3,4-dihydroxyphenyl)- D,L -α-alanine-1-11C (11C-DOPA), using 11CO2 as the radioactive precursor is described. Carboxylation of an α-lithioisocyanide, containing protected hydroxylic groups, was followed by a three-step hydrollsis of the intermediate α-isocyano carboxylic acid. Preliminary experiments in rats indicate that the compound is preferentially decarboxylated in brain areas rich in dopamine containing neurons.

Of the cyclotron-produced short-lived isotopes carbon-11 (t12 = 20.4 min; β+) is one of the most promising as label for radiopharmaceuticals. To prepare 11C-labelled amino acids for evaluation as pancreas scanning agents a new rapid amino acid synthesis was developed. The method is based on the carboxylation of α-lithioisocyanides with 11CO2, followed by hydrolysis of the intermediate reaction product to the desired amino acid. By this method DL-α-phenylalanine-1-11C and DL-α-phenylglycine-1-11C were prepared. The precursor 11CO2 was produced via the 14N(p, α)11C reaction by bombardment of a flow of nitrogen gas mixed with 0.1% O2 with 20 MeV protons. The target system is described.

Wash-in curves for physiologically inert gases are usually described by a mono-exponential function of the type N(t) = N∞(l−e−kt). N∞ is related to lung volume and K is the specific alveolar ventilation, or alveolar ventilation per unit lung volume. Determination of the specific alveolar ventilation therefore recess takes an estimate of ? from the measured curve. Compared with other gases Xenon-133 is fairly soluble in blood (blood-gas partition coefficient λ = 0.152). This gives rise to multiexponential curves3.

No-carrier-added DL -[1- 11 C]-DOPA has been synthesized by carboxylation of an α-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.

A semiquantitative method for evaluating the splenic uptake of 111In is described. With this method the uptake of indium in the spleen was significantly higher in seven patients with extramedullary erythropoiesis (EME) than in a control group of seven patients with comparable degrees of splenomegaly but without clinical and/or histological signs of EME. The discrimination between these groups could be further improved by also taking the degree of splenomegaly into account. It is concluded that the described technique is a valuable non-invasive aid for establishing the presence of EME in the spleen.

Vitamin B12 was assayed by the competitive protein binding method, using Lactobacillus leichmannii as binding agent. The intact bacteria were used as “solid phase”, and separation of bound and free vitamin B12 was obtained simply by filtration of the bacteria. Filtration could be rapidly done using a disposable syringe provided with a filter. Optimal conditions with respect to the extraction of vitamin B12 from serum and binding of the vitamin to the bacteria were determined. The effect of several drugs and hormones on the assayed vitamin B12 concentration was investigated. The correlation with the Lactobacillus leichmannii bioassay was calculated.

Carbon-11 labelled glycine has been prepared in 30 min by carboxylation of α-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 11 CO 2 , non carrier added L -phenylalanyl[1- 11 C]glycine and L -leucyl[1- 11 C]glycine in 0.1 N NaH 2 PO 4 were obtained in 50 min with a radiochemical yield of 3–6%. The radiochemical yield figures are not corrected for decay.

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.

A method for the production of 13NN either as a gas or as an injectable solution is described. The method is based on the 16O(p,α)13N reaction and water as target material. Following irradiation, the 13NO2- and 13NO3- are reduced to 13NH3, followed by NaOBr oxidation to 13NN. With a beam current of 1 μA and 20 min irradiation time the injectable solution contained 148 MBq (4 mCi) per ml.

Based on a theoretical evaluation of the charged particle induced reactions leading to 75 Br the four most promising reactions, 76 Se (p,2n) 75 Br , 76 Se (d,3n) 75 Br , 75 As ( 3 He ,3n) 75 br and 75 As ( 4 He ,4n) 75 Br , were selected for excitation function measurements. From the measured excitation functions the production rates and radionuclide purities were calculated. The proton induced reaction on 76 Se showed the highest production rate (118 mCi/μAh) while the contamination of the undesired nuclide 76 Br is limited to 1.4%.

A rebreathing technique is described for measuring FRC during exercise. Good agreement was found between this technique and a standard helium dilution method using a water spirometer at rest. Measurements of FRC in ten volunteers showed a significant decrease of FRC at the onset of progressive exercise. The FRC remained significantly smaller than the resting value up to loads of 150 W.

A new radioimmunoassay for plasma testosterone in human blood plasma is described. The assay is performed directly upon the plasma without extraction and purification of the testosterone. Antibodies to testosterone-7α-carboxyethyl thioether-bovine serum albumin are used and data concerning the specificity of these antibodies are given.

Antibodies have been evoked against vitamin B 12 conjugates using two types of antigen: intrinsic factor saturated with vitamin B 12 and vitamin B 12 covalently coupled to albumin. The antibodies were purified by rivanol and identified by polyacrylamide gel electrophoresis. Purified and unpurified anti-bodies were both applied in a radioimmunoassay for vitamin B 12 . Affinity chromatography proved to be a useful method for purification of the vitamin B 12 antibodies. An immunoadsorbent of vitamin B 12 covalently coupled to aminoethylcellulose was used.

The aim of this investigation was to find a scintillation mixture for counting up to 1 ml of plasma. We succeeded in obtaining a mixture of xylene/Triton X-100/mono- and di-butylphosphate, and called it Plasmasol. The properties were ideal for radioimmunoassays of steroids. Good dissolving properties, high counting efficiency, absence of chemiluminescence and a good stability and reproducibility with respect to the disintegrations per minute were achieved. The cost was only 25% of the commercially available ready-to-use liquid scintillation mixtures, with which a comparison was made.

The theory of the measurement of the specificity of antigen binding by antibodies is reviewed. The specificity of steroid immunoassay has been investigated using a new solid phase radioimmunoassay system. The effects of plasma proteins on the specificity of the immunoassays have been tested. The methods used and the conclusions reached have been tested with homogeneous antibodies in order to simplify the interpretation of the results obtained. A new criterium of antibody homogeneity is proposed. The importance of correcting all results accurately for “non-specific binding” is emphasised. A new method for plotting radioimmunoassay standard curves is presented.

dl -[1-11C]methionine has been synthesized by carboxylation of the corresponding α-lithioisocyanide with a radiochemical yield of 8–14% (EOS, 35 min).