The biological and medical importance of the isotope 252-californium: International Symposium on Californium.
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A commercial antacid suspension containing aluminum hydroxide and magnesium hydroxide products was used as a model sample to study the use of a californium-252 thermal neutron activation as a method for quantifying aluminum content as well as for the simultaneous assay of aluminum and magnesium. A 3.5-micrograms californium-252 source was used for the activation, and the induced aluminum-28 and magnesium-27 activity was simultaneously measured by sodium iodide crystal gamma-ray spectrometry using dual single-channel analyzers and scalers. The antacid suspension was contained in a chamber designed with the unique capability of serving as the container for counting the induced radioactivity in addition to being the irradiation chamber itself. Ten replicate irradiations were performed, and the precision was compared with 10 replicate analyses of the antacid suspension using the official ethylenediaminetetraacetic acid titration method. For aluminum the precision was 1.4 versus 0.62% for the titration method. For the magnesium the precision was 5.3 versus 0.79% for the titration method. This pilot study demonstrated that use of more intense californium-252 sources, which are commonly available, would provide a method that is competitive with the ethylenediaminetetraacetic acid titration method in precision and in other aspects as well.
The radioisotope 252Cf is routinely encapsulated into compact, portable, intense neutron sources with a 2.6-yr half-life. A source the size of a person's little finger can emit up to 10(11) neutrons s(-1). Californium-252 is used commercially as a reliable, cost-effective neutron source for prompt gamma neutron activation analysis (PGNAA) of coal, cement and minerals, as well as for detection and identification of explosives, land mines and unexploded military ordinance. Other uses are neutron radiography, nuclear waste assays, reactor start-up sources, calibration standards and cancer therapy. The inherent safety of source encapsulations is demonstrated by 30 yr of experience and by US Bureau of Mines tests of source survivability during explosions. The production and distribution center for the US Department of Energy (DOE) Californium Program is the Radiochemical Engineering Development Center (REDC) at Oak Ridge National Laboratory (ORNL). DOE sells 252Cf to commercial reencapsulators domestically and internationally. Sealed 252Cf sources are also available for loan to agencies and subcontractors of the US government and to universities for educational, research and medical applications. The REDC has established the Californium User Facility (CUF) for Neutron Science to make its large inventory of 252Cf sources available to researchers for irradiations inside uncontaminated hot cells. Experiments at the CUF include a land mine detection system, neutron damage testing of solid-state detectors, irradiation of human cancer cells for boron neutron capture therapy experiments and irradiation of rice to induce genetic mutations.
We carried out radiotracer experiments on the behaviour of 252Cf in the marine environment. The particulate fraction of californium in sea water approached 45% after four days. Californium rapidly adsorbed onto marine coastal and deep-sea sediments with Kd values from 1.4 X 10(4) to greater than or equal to 1 X 10(5). The concentration of 252Cf in euphausiids reached near-equilibrium factors of 3 X 10(2) in water after one week; in contrast, the assimilation from food was very low. Excreted fecal pellets, molts and zooplankton carcasses are potentially important vectors for californium re-distribution in the oceans.
Intracavitary Californium-252 combined with whole-pelvis photon radiotherapy was tested as the sole form of treatment for 22 patients with Stage IB carcinoma of the cervix. Californium-252 (Cf) is a fast neutron-emitting radioisotope currently being tested in trials of neutron brachytherapy (NT). The outcomes of the treated group of patients were traced for local tumor control, survival, patterns of failure, and complications. The Cf intracavitary therapy combined with whole-pelvis photon radiotherapy resulted in 95% 2-year and 91% 5-year actuarial survival. There were 9% Grade II-III complications by the Stockholm scale and 4% local failures. These results were obtained in an early clinical trial with a group of largely poor-risk patients with tumors of mean diameter of 4.3 cm.
Details of clinical apparatus designed for the measurement of total body nitrogen (as an indicator of body protein), suitable for the critically ill, intensive-care patient are presented. Californium-252 radio-isotopic neutron sources are used, enabling a nitrogen measurement by prompt neutron activation analysis to be made in 40 min with a precision of +/- 3.2% for a whole body dose equivalent of 0.145 mSv. The advantages of Californium-252 over alternative neutron sources are discussed. A comparison between two irradiation/detection geometries is made, leading to an explanation of the geometry adopted for the apparatus. The choice of construction and shielding materials to reduce the count rate at the detectors and consequently to reduce the pile-up contribution to the nitrogen background is discussed. Salient features of the gamma ray spectroscopy system to reduce spectral distortion from pulse pile-up are presented.
Californium-252 which emits fission neutrons and gamma rays is being investigated for applications in brachytherapy. From available experimental results, a value of 6.2 had been arrived at as the RBE for cell killing of californium neutrons relative to radium gavva rays for intracavitary applications based on the revised Manchester system of loading. The LET distributions as well as the ratio of neutron to gamma dose-rates have been estimated and are found to remain almost constant in the volume of interest around such applications.
From June 1977 to June 1983, 32 patients with bulky (greater than 4 cm diameter), barrel-shaped Stage IB cervical cancer were treated at the University of Kentucky Medical Center by a combination of outpatient neutron brachytherapy using californium 252 (252Cf) and external pelvic radiation followed by extrafascial hysterectomy. Nineteen patients had cervical tumors 4 to 6 cm in diameter, and 13 patients had lesions in excess of 6 cm in diameter. A dose of 4500 rad external photon therapy was given from a linear accelerator, and one or two 6-hour 252Cf implants were given during or immediately after external radiation. Extrafascial hysterectomy with bilateral salpingo-oophorectomy was performed 6 weeks after completion of radiation therapy. Complications during and after radiation were minimal and included vaginal stenosis (three) and proctitis (two). Tumor clearance in the hysterectomy specimen was complete in 23 patients (72%) and residual cervical tumor was present in 9 patients (28%). Two patients developed tumor recurrence and died of disease 15 and 27 months after therapy, respectively. Thirty patients remain free of disease 26 to 96 months (median, 52 months) after treatment, and none have been lost to follow-up. The actuarial survival of these patients is 97% at 2 years and 94% at 5 years. Intracavitary neutron therapy is well tolerated and is effective when combined with external radiation and hysterectomy in the treatment of bulky, barrel-shaped Stage IB cervical cancer.
From January 1977 to July 1984, 32 patients with Stage IIIB cervical cancer were treated at the University of Kentucky Medical Center by a combination of outpatient neutron brachytherapy and external pelvic radiation. These patients received 4500 to 5000 rad external photon therapy and two or three outpatient Californium-252 (252Cf) implants, plus sidewall boost irradiation. Treatment results were compared retrospectively to those obtained in a historical control group of patients with Stage IIIB cervical cancer treated with external radiation and conventional photon brachytherapy from 1972 to 1976. Local or regional tumor recurrence developed in 53% of patients treated with neutron therapy and an additional 9% experienced distant metastases. Thirty-eight percent of patients remain free of disease 12 to 96 months (mean, 51 months) after therapy. The 2-year and 5-year survival rates of patients treated with neutron therapy were 53% and 36%, which were not significantly different than those obtained with photon brachytherapy (2-year survival, 61%; 5-year survival, 34%). Complications of neutron therapy were minimal and included proctitis (19%) and vaginal stenosis (9%). There were no cases of enteric fistulae. Outpatient neutron brachytherapy was cost effective and was well tolerated by patients.
Twenty patients with Stage IVA and IVB cervic cancers were treated with Californium-252 (Cf) neutron brachytherapy (NT) in a feasibility trial between 1976 and 1986. Eleven patients had Stage IVA disease; nine patients had Stage IVB disease. Patient compliance with therapy was poor in four of nine patients with Stage IVB disease, and the 50% survival time was 6 months. In Stage IVA disease there were 18% 3-year survivals. For those that failed, the 50% survival time was 7.5 months. Because of the frequency of disseminated metastases, effective adjuvant therapy needs to be developed to use after the tumor debulking therapy, especially for Stage IVB disease. A single early Cf-NT implant followed by 6000 cGy of whole-pelvis fractionated radiation would accomplish this adequately for local tumor control and palliation.
Since 1976 a clinical trial has been conducted to test the feasibility, the potential, and to develop methods for using the neutron-emitting radioactive isotope, californium-252 (Cf-252), for the treatment of cervical cancer. A total of 218 patients were treated in the initial study period from 1976 until 1983. The trials initially treated advanced (Stages III and IV) cervical cancer patients using different doses and schedules; they were extended to include unfavorable presentations of Stages I and II because of favorable results in the initial trials. The authors began to treat patients with Stage IB bulky or barrel-shaped tumors and the majority were treated with both radiation and hysterectomy. Actuarial survival was determined for Stage IB disease and was 87% at 5 years and 82% at 10 years. For those tested with preoperative radiation it was 92% at 5 and 87% at 10 years. For Stage II, it was 62% 5 years and 61% at 10. Survival 5 years after combined radiation and surgical therapy for Stage II disease was 68%. For Stage III, it was 33% at 5 years and 25% at 10. However, 5-year survival using the early neutron implant was 46% versus approximately 19% for delayed Cf-252 or cesium 137. Different schedules and sequences of neutrons and photons greatly altered outcome. Neutron treatment before external photon therapy was better for all stages of disease. Only about 5% of all patients developed complications after neutron therapy. No hematologic or mesenchymal second tumors were observed. Neutron brachytherapy was found to be very effective for producing rapid response and greatly improved local control of bulky, barrel, or advanced cervical cancers. The clinical trial identified and evolved schedules, doses, doses per session, and developed methods different from standard photon therapy but highly effective for local control and cure of cervical cancers of all stages. Clinical and radiobiologic understanding for the use of neutron therapy was greatly advanced by this trial. Future trials will focus on patients with advanced disease and will require evaluation of adjuvant chemotherapy studies and neutron-enhancing chemicals.
Californium-252 plasma desorption mass spectrometric analysis of complex lipooligosaccharide antigens from Mycobacterium kansasii has provided molecular weight information. From the spectra obtained and from other data it can be concluded that these lipooligosaccharides generally contain three 2,4-dimethyltetradecanoyl groups, and considerable heterogeneity in the attached acyl functions is apparent.
Commercial digitonin has been separated into its components using high-performance liquid chromatography and centrifugal countercurrent chromatography. The individual glucosides have been identified by californium-252 plasma desorption mass spectrometry, occasionally supplemented by hydrolysis and analysis of the liberated sugars and aglycones. Mass spectra of commercial digitonin that have appeared in the literature are discussed in the light of their complex nature. A new glycoside of molecular weight 1035 is described and a structure proposed.
Californium-252 plasma desorption mass spectra have been run on a series of typical lipids found in skin, including a fatty acid, a methyl and wax ester, a mono-, di- and triglyceride and an anhydride, in a effort to discover the nature of peaks caused by fingerprint contamination of the sample holders. The triglyceride was identified as the source, and peaks found by reattachment of abundant fragment ions to the original lipid were noted in several cases.
252-Californium plasma desorption mass spectrometry was applied to the study of five different classes of phospholipids namely phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylserine and phosphatidylinositol. Positive and negative ion spectra were compared to spectra obtained using other ionization techniques. Plasma desorption mass spectra provide useful information on the molecular weight of compounds from all classes, particularly in the case of phosphatidylserine--a class that has failed to show satisfactory quasimolecular ions with either Fast atom bombardment, FAB or Field desorption, FD. The observed fragmentation is also indicative of the structure of the studied compounds.
This paper presents mass spectral data of eleven aminoglycoside antibiotics by using californium-252 plasma desorption (252Cf PD) mass spectrometry. This mass spectral data could be used to develop a confirmatory method for monitoring aminoglycoside antibiotic residues isolated from food products of animal origin. Mass spectra were determined by applying time-of-flight 252Cf PD mass spectrometry to eleven aminoglycoside antibiotics, namely: neomycin, kanamycin, paromomycin, tobramycin, apramycin, streptomycin, dihydrostreptomycin, amikacin, netilmicin, sisomicin and gentamicins. All eleven antibiotics yielded positive ion spectra. These hydrophilic antibiotics were derivitized to extractable chromopheric compounds. All but two antibiotics (streptomycin and dihydrostreptomycin) yielded nitrophenyl derivatives and spectra were obtained in both negative and positive ion modes. Derivatized aminoglycosides produced cation and anion spectra with quasimolecular ions corresponding to [M + H]+., M+, [M - H]-., [M + Na]+, [M + K]+ and M-. or [M - H]- and M-. or [M - H]-. Underivatized antibiotics were best examined in the positive ion mode. 252Cf PD mass spectrometry consistently produced very strong molecular or quasimolecular ions for all aminoglycoside antibiotics.
The effects of californium-252 radiation (average neutron energy E = 2.13 MeV) were investigated using mouse leukemia L5178Y cells. No dose-rate effect was detected for cell killing, but a 'reversed' dose-rate effect was observed for mutation induction. The frequency of 6-thioguanine-resistant mutations increased linearly up to 100 cGy (1 Gy = 100 rad), then began to level off at a dose rate of 1.2 cGy/min, while it increased continuously up to 200 cGy at a reduced dose rate of 0.16 cGy/min. Compared with results obtained using 60Co gamma-rays, the ratio of the initial slope of each dose-response curve was 4-5 for cell killing, and more than 11 for mutagenesis. Since one-third of 252Cf radiation consists of gamma-rays, the relative biological effectiveness (RBE) of 252Cf neutrons would be even greater, 16 or more, for mutation induction in the present assay.
Californium-252 promises to be an effective radium substitute in brachytherapy. In certain situations, such as cancer of the uterus, the dose rate near a linear source may be of interest. Paterson and Parker have tabulated the number of milligram hours for various active lengths of radium sources to give 1000 rad at different distances from the centre of the source. This paper presents similar results for Cf-252 (microgram hours to give 1000 rad neutron dose). The paper also reports the results of experimental measurements of neutron depth dose distributions for both single line sources and arrays. Kodak NTA films and a phantom were used for the study. The experimental results are found to agree well with the theoretically predicted results.