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Rhenium-188--a generator-derived radioisotope for cancer therapy.

Rhenium-188 (188Re) is an important therapeutic radioisotope which is obtained on demand as carrier-free sodium perrhenate by saline elution of the tungsten-188/rhenium-188 generator system. With a half-life of 16.9 hours and emission of a high energy beta particle (maximal energy of 2.12 MeV) and a gamma photon (155 keV, 15%) for imaging, 188Re can be provided at reasonable costs for routine preparation of radiopharmaceuticals for cancer treatment.

Half-Life↗

Effects of antineoplastic drugs on Lactobacillus casei and radioisotopic assays for serum folate.

Microbiologic assay, usually employing Lactobacillus casei, remains the standard assay for serum folate to date. Among its disadvantages have been falsely low results in patients receiving bacteriostatic agents such as antibiotics. This study examined whether commonly used antineoplastic drugs had similar effect. Methotrexate and 5-fluorouracil depressed microbiologic serum folate levels. No effect was found for adriamycin, bleomycin, BCNU, cyclophosphamide, cytosine arabinoside, vincristine, vinblastine, mechlorethamine, mithramycin, hydroxyurea, and hydrocortisone. None of the drugs affected radioassay except methotrexate, which produced falsely high folate results. Thus, it appears that L. casei assay for folate becomes unreliable in patients receiving 5-fluorouracil and radioisotopic assay becomes unreliable in those receiving methotrexate.

Antineoplastic Agents↗

Radiolabeled microorganisms: comparison of different radioisotopic labels.

Radioactively labeled microorganisms are very useful in assessing the in vitro phagocytic capability of human granulocytes and macrophages. Since microorganisms contain amino acids and nucleic acids, they can be radiolabeled by addition of radioactive amino acid and/or nucleic acid components to the culture medium. The isotopes 3H, 14C, 32P, 35S, and 75Se-have been used for bacterial radiolabeling. All of these commonly used isotopes with the exception of 75Se are beta emitters; 75Se is a gamma emitter. The half-lives of these isotopes vary from 14 days for 32P to 5,730 years for 14C. Because of the differences in their physical properties, they pose very different handling problems and require different kinds of safety precautions. In the event of either external or internal contamination, beta emitters deliver a larger localized radiation dose than do gamma emitters. In the case of internal contamination, the radiation dose increases with increases in the half-life of the radioactive isotope. Gamma radiation, on the other hand, is more penetrating than are beta particles and thus a gamma emitter requires appropriate shielding. Both the cost and the special problem of manipulation associated with these radioactive chemicals should be carefully considered before deciding which radioisotope is preferable for the labeling of microorganisms in the laboratory. In spite of the limitations of 75Se as a nonphysiologic element, it offers the simplest methods of handling among the isotopes considered in this review.

Bacteria↗

Comparative measurement of zinc absorption in rats with stable isotope 70Zn and radioisotope 65Zn.

The use of stable isotopes in a study on zinc bioavailability was evaluated in rats by comparing the zinc absorption of a stable isotope 70Zn and a radioisotope 65Zn simultaneously. The rats of low zinc status were obtained by feeding 1.2% phytic acid from sodium phytate and 12 ppm zinc from zinc sulfate in a semipurified diet for 14 days. The rats were then randomly assigned into five groups of ten rats. The rats were intubated with a test diet mixture with a phytate:zinc molar ratio of 0, 6.25, 12.5, 25 or 50 along with one microCi of 65Zn and 0.02 mg of 70Zn in 2.5 ml of intubating solution. Four hours after the intubation, rats were allowed to consume the diets having the same phytate:zinc ratio as used for intubation ad libitum. Feces were collected every 24 hours for a total of 168 hours. The 65Zn and 70Zn content of diets and fecal samples were determined and the percent of zinc absorption was calculated. The results of this study indicated that the zinc absorption determined by these two isotopes were highly correlated with a correlation coefficient ratio of 0.914.

Absorption↗

Dietary oxidized frying oil enhances tissue alpha-tocopherol depletion and radioisotope tracer excretion in vitamin E-deficient rats.

Rats fed a diet containing 15% oxidized frying soybean oil (OFO) have been shown to have significantly lower tissue alpha-tocopherol (alpha-T) concentration than rats fed a 15% fresh soybean oil diet. To examine the turnover of alpha-tocopherol, a depletion-repletion experiment and a radioisotope tracer study were conducted. Two groups of male weanling Long-Evans rats were fed vitamin E-deficient diets containing either 15% OFO or 15% vitamin E-stripped fresh soybean oil (control). After 9 wk of depletion, rats fed the OFO diet had significantly higher plasma pyruvate kinase (PK) activity and lower concentrations of alpha-T in RBC, adrenal gland, heart, kidney, liver, spleen, testis and muscle compared with controls (P < 0.05), indicating that the vitamin E-deficient status was aggravated by feeding the OFO diet. After 12 wk, the depleted rats were intraperitoneally injected with a dose of all-rac-alpha-T (2.5 mg/rat, dissolved in Vitamin E-stripped corn oil) every other day. Three doses were administered to each rat during the 1-wk repletion period. Plasma PK activity decreased in both groups (P < 0.05) after repletion but that of the OFO rats was still significantly higher than that of the control group. The repleted OFO gorup also had significantly lower alpha-T concentration in adrenal gland, epididymal fat, liver and spleen than the repleted control group. Two rats from each group that had been vitamin E-depleted for 16 wk were injected intraperitoneally with a single dose of 5-methyl-14C-RRR-alpha-T (740 kBq/kg body weight). During the week after dosing, the radioactivity excreted in urine and feces of the OFO group was 1.3- and 1.7-fold, respectively, that of the control group. Tissue retention of radioactivity was also lower in the OFO rats than in the control rats. The results suggest that more of the alpha-T in the body was catabolized or turned over in rats fed the OFO-containing diet.

Adrenal Glands↗

New radioisotopic assays of argininosuccinate synthetase and argininosuccinase.

Methods were developed for the radioisotopic assay of argininosuccinate synthetase [L-citrulline: L-aspartate ligase (AMP-forming), EC 6.3.4.5] and argininosuccinase [L-argininosuccinate arginine-lyase, EC 4.3.2.1]. The assay of argininosuccinate synthetase was based on the separation of [14C]argininosuccinate formed from aspartate and [carbamoyl-14C]citrulline in the presence of ATP from the substrate citrulline. For this, the product was converted to its anhydride form by boiling for 30 min at pH 2.0 followed by application on a column of Dowex 50W (pyridine form). Argininosuccinic anhydride was eluted with 0.3 M pyridine acetate buffer, pH 4.25, while citrulline was eluted with 0.1 M pyridine acetate buffer, pH 3.80. The assay of argininosuccinase was based on the separation of [14C]argininosuccinic acid formed from arginine and [U-14C]fumaric acid from the substrate fumarate on a column of Dowex 50W(H+ form). The argininosuccinic acid was adsorbed on the column and eluted with 1 M pyridine solution, while fumarate was not adsorbed. The distributions of these two enzymes in various organs and cell fractions were reinvestigated using these methods.

Animals↗

Metabolic intervention in surgical patients. An assessment of the effect of somatostatin, ranitidine, naloxone, diclophenac, dipyridamole, or salbutamol infusion on energy and protein kinetics in surgical patients using stable and radioisotopes.

We have assessed the effect of a variety of forms of metabolic intervention on both energy and protein metabolism in 44 severely ill surgical patients. The patients were studied either in the basal state or while receiving total parenteral nutrition (TPN), and the metabolic effects were assessed using the primed-constant infusion of a combination of stable isotopes and radioisotopes. Somatostatin infusion, either in the basal state or in the TPN, did not change glucose kinetics, but there was a significant decrease in the rate of net protein catabolism (NPC). In the basal studies the rate of NPC decreased from 3.4 +/- 0.7 g/kg/d to 2.9 +/- 0.7 g/kg/d (p less than 0.002), while in the TPN patients the corresponding values were 1.48 +/- 0.61 g/kg/d and 1.10 +/- 0.50 g/kg/d, respectively (p less than 0.005). Histamine type 2 blockade with ranitidine did not significantly alter glucose kinetics, but in both the TPN patients and in the basal state ranitidine was associated with a significant decrease in the rate of NPC. In the basal state rate of NPC was 2.44 +/- 0.53 g/kg/d and during ranitidine infusion the value was 2.08 +/- 0.42 g/kg/d (p less than 0.04). Naloxone infusion did not alter glucose kinetics, but there was a significant decrease in the rate of NPC from a basal value of 2.6 +/- 0.6 g/kg/d to 2.3 +/- 0.5 g/kg/d (p less than 0.04). The infusion of the prostaglandin antagonists diclofenac or dipyridamole resulted in increases in the plasma insulin level, and as a result glucose turnover decreased in both groups. In the diclofenac group the rate of glucose turnover decreased from 14.4 +/- 1.7 mumol/kg/min to 12.6 +/- 1.3 mumol/kg/min (p less than 0.02). Neither prostaglandin antagonist resulted in any significant change in the rate of NPC. Beta-adrenergic stimulation with salbutamol resulted in a significant increase in glucose turnover from 12.1 +/- 1.1 mumol/kg/min to 13.4 +/- 0.9 mumol/kg/min (p less than 0.02), and the rates of appearance (Ra) of both alanine and free fatty acids (FFAs) also increased. Alanine Ra increased from 11.7 +/- 2.5 mumol/kg/min to 12.8 +/- 3.0 mumol/kg/min, and the corresponding values for FFA turnover were 7.6 +/- 1.1 mumol/kg/min and 10.3 +/- 2.1 mumol/kg/min (p less than 0.03), respectively. Salbutamol infusion did not result in any significant change in the rate of NPC.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Neutron dosimetric quantities for several radioisotopic neutron sources.

The fluence-weighted and dose equivalent-weighted average energies, and the spectrum-averaged fluence-to-dose equivalent conversion factors have been calculated for 52 spectrum variations of 20 different radioisotopic neutron sources. An internally consistent method of determination enables comparison of values for different spectra. The methodology and results are presented.

Neutrons↗

Radioisotope laboratory audits.

Elsewhere in this issue, Robin Elliott outlined a successful program for performing annual radiation safety management program audits. The results of such audits provide a useful means of evaluating and correcting deficiencies or weaknesses in a radiation safety program. At our institution we also perform an annual audit of each radioisotope lab oratory for the same reasons.

Humans↗

A survey of close contact regimes between patients undergoing diagnostic radioisotope procedures and children.

When following diagnostic radioisotope procedures, UK legislation requires that we advise patients to avoid close contact with children [1, 2]. How does this advice affect the average nuclear medicine patient? Over a 4 month period, 90 patients in contact with children were asked about their home circumstances, how they coped with avoidance of close contact and the problems caused. On average, the patients were in contact with two children with a mean age of 7 years. Thirty-nine per cent of patients spent < 5 h per day and 30% between 5 and 10 h per day in close contact. However, 13% spent 20-24 h in close contact with children. For most patients (55%), it is easy to avoid close contact, but 25% found it difficult or very difficult. The average in-patient received one visit a day from children of 0.5-1 h duration and 65% of children sat on the patient's bed. Restriction of visits was a problem for 14% of patients. Initially, over one-third of the out-patients felt a medium level of anxiety or higher regarding close contact with children. Given more detailed written information and the opportunity to discuss any queries with a member of staff (70% wished to do so), the proportion fell to less than one-tenth. We found it important to question patients carefully, because home circumstances and levels of close contact cannot be deduced from the age of the child or the relationship between the child and the patient.

Adolescent↗

Implanted artificial heart with radioisotope power source.

An atomic artificial heart for orthotopic implantation was developed with the following characteristics: volume, 1.2 L; weight, 1.5 kg; radioisotope power, 45 W; operating life, up to 5 years; hemodynamics, similar to natural hemodynamics. The artificial heart includes a thermal drive with systems for regulating power, feeding steam into the cylinders, return of the condensate to the steam generator, and delivery of power to the ventricles and heat container. The artificial heart is placed in an artificial pericardium partially filled with physiologic solution. It uses a steam engine with two operating cylinders that separately drive the left and right ventricles. There is no electronic control system in the proposed design. The operation of the heat engine is controlled, with preservation of autoregulation by the vascular system of the body. The separate drives for the ventricles is of primary importance as it provides for operation of the artificial heart through control of cardiac activity by venous return. Experimental testing on a hydromechanical bench demonstrated effective autoregulation.

Electric Power Supplies↗

Radioisotopic, culture-based, and oligonucleotide microchip analyses of thermophilic microbial communities in a continental high-temperature petroleum reservoir.

Activity measurements by radioisotopic methods and cultural and molecular approaches were used in parallel to investigate the microbial biodiversity and its physiological potential in formation waters of the Samotlor high-temperature oil reservoir (Western Siberia, Russia). Sulfate reduction with rates not exceeding 20 nmol of H(2)S liter(-1) day(-1) occurred at 60 and 80 degrees C. In upper horizons (AB, A, and B), methanogenesis (lithotrophic and/or acetoclastic) was detected only in wells in which sulfate reduction did not occur. In some of the wells from deeper (J) horizons, high-temperature sulfate reduction and methanogenesis occurred simultaneously, the rate of lithotrophic methanogenesis exceeding 80 nmol of CH(4) liter(-1) day(-1). Enrichment cultures indicated the presence of diverse physiological groups representing aerobic and anaerobic thermophiles and hyperthermophiles; fermentative organotrophs were predominant. Phylogenetic analyses of 15 isolates identified representatives of the genera Thermotoga, Thermoanaerobacter, Geobacillus, Petrotoga, Thermosipho, and Thermococcus, the latter four being represented by new species. Except for Thermosipho, the isolates were members of genera recovered earlier from similar habitats. DNA obtained from three samples was hybridized with a set of oligonucleotide probes targeting selected microbial groups encompassing key genera of thermophilic bacteria and archaea. Oligonucleotide microchip analyses confirmed the cultural data but also revealed the presence of several groups of microorganisms that escaped cultivation, among them representatives of the Aquificales/Desulfurobacterium-Thermovibrio cluster and of the genera Desulfurococcus and Thermus, up to now unknown in this habitat. The unexpected presence of these organisms suggests that their distribution may be much wider than suspected.

Archaea↗

Radioisotope assay for the quantification of sulfate-reducing bacteria in sediment and water.

A radioisotope enrichment culture method was developed to estimate the physiologically active component of a population of sulfate-reducing bacteria in environmental water and sediment samples. Aliquots of water or sediment were added to 50-ml serum bottles filled with 35-S-sulfate broth incubated for approximately 30 h. After incubation, the disintegration rate per milliliter of spent medium was measured, and the percentage of loss of activity resulting from bacterial sulfate reduction was determined. This loss of sulfate from the medium was then translated to a specific number of Desulfovibrio desulfuricans cells that would reduce an equivalent amount of sulfate in the same incubation time. This comparison was done using a series of growth curves of D. desulfuricans covering a range of inoculum densities between 10-2 and 10-7 cells. The radioassay was used to follow the effects of a pulp mill on a small anoxic river in Florida. The activity of the sulfate-reducing bacteria in the river was greatly suppressed when the mill was closed for annual maintenance. The initiation of waste treatment resulted in improved water quality in 1 week, but the river sediments required a month to show a 10-fold reduction in the population of sulfate-reducing bacteria.

Bacteria↗

Criteria in radioisotope detection of venous thrombosis.

Forty-one patients out of a larger series undergoing elective surgery were examined for the presence of venous thrombosis in the legs by means of the (125)I-fibrinogen technique. The radioisotope data were analysed by three different methods. The percentage uptake was calculated and, by the generally accepted difference of 15%, 22 patients had evidence of thrombosis. The statistical index, which takes account of the errors due to radioactivity counting inherent in the percentage uptake calculation, indicated thrombosis in 36 patients. The relative uptake index, which allows for the errors due to unequal distribution of radioactivity throughout the normal limb as well as the errors due to radioactivity counting, provided evidence of thrombosis in a total of 34 patients, compared with only 22 patients when assessed by the "15%" criterion.

Diagnostic Errors↗

An evaluation of commercial radioisotope methods for the determination of folate and vitamin B12.

Five commercial kits for the determination of folate and six kits for the determination of vitamin B12 were investigated. Their performance has been compared with microbiological methods for the two vitamins and with a non-commercial radioisotopic method for B12. The results show the importance of the determination of the reference range for an individual laboratory for each method. The precision of the kits varied appreciably, as did their performance using specimens from patients with different haematological disorders. In particular, certain kits failed to detect all patients with pernicious anaemia. The relative accuracy of the kits was assessed. Various factors which should be taken into account in the final selection of a satisfactory kit are discussed.

Anemia, Pernicious↗

Forms of vitamin B12 in radioisotope dilution assays.

Since the presence of analogues of vitamin B12 (B12, cobalamin, Cbl) has been postulated as the basis for the high values obtained by some radioisotope dilution assays (RIDA) of serum Cbl we examined serum for analogues. None could be demonstrated in the extracts of serum prepared for RIDA as sought by both direct and indirect techniques. The natural forms of serum Cbl were converted to cyanocobalamin (CN Cbl) by this process of extraction which included cyanide (CN). The correctly performed RIDA for Cbl based on R binder gave higher values than a RIDA based on intrinsic factor or than by bioassay. By exclusion, the difference appeared to be due to unidentified factors rather than the presence of analogues.

Chromatography, Gel↗

The radioisotope contributes significantly to the activity of radioimmunotherapy.

PURPOSE: A multicenter, randomized study was undertaken to estimate the single agent activity of Tositumomab and to determine the contribution of radioisotope-labeling with (131)I to activity and toxicity by comparing treatment outcomes for Tositumomab and Iodine I 131 Tositumomab (BEXXAR) to an equivalent total dose of unlabeled Tositumomab. EXPERIMENTAL DESIGN: Seventy-eight patients with refractory/relapsed non-Hodgkin's lymphoma were randomized to either unlabeled Tositumomab or Iodine I 131 Tositumomab. Patients progressing after unlabeled Tositumomab could cross over to receive Iodine I 131 Tositumomab. The median follow-up at analysis was 42.6 months (range 1.9 to 71.5 months). RESULTS: Responses in the Iodine I 131 Tositumomab versus unlabeled Tositumomab groups: overall response 55% versus 19% (P = 0.002); complete response 33% versus 8% (P = 0.012); median duration of overall response not reached versus 28.1 months (95% confidence interval: 7.6, not reached); median duration of complete response not reached in either arm; and median TTP 6.3 versus 5.5 months (P = 0.031), respectively. Of the patients who had a complete response after initial Iodine I 131 Tositumomab therapy, 71% (10 of 14) continued in complete response at 29.8 to 71.1 months. Two patients who achieved a complete response after unlabeled Tositumomab had ongoing responses at 48.1 to 56.9 months. Nineteen patients received Iodine I 131 Tositumomab crossover therapy. Responses after crossover versus prior response to unlabeled Tositumomab were as follows: complete response rates of 42% versus 0% (P = 0.008); overall response 68% versus 16% (P = 0.002); median durations of overall response 12.6 versus 7.6 months (P = 0.001); and median TTP 12.4 versus 5.5 months (P = 0.01), respectively. Hematologic toxicity was more severe and nonhematologic adverse events were more frequent after Iodine I 131 Tositumomab than after Tositumomab alone. Elevated thyrotropin occurred in 5% of patients. Seroconversion to human antimurine antibody after Iodine I 131 Tositumomab, unlabeled Tositumomab, and Iodine I 131 Tositumomab-crossover was 27%, 19%, and 0%, respectively. CONCLUSIONS: Unlabeled Tositumomab showed single agent activity, but in this direct comparison, all of the therapeutic outcome measures were significantly enhanced by the conjugation of (131)I to Tositumomab.

Adult↗

Effect of increased intrareservoir pressure on upper urinary tract function in continent urinary diversion patients assessed by radioisotope renography.

To assess upper urinary tract function and determine an ideal continent reservoir capacity, we investigated the relationship between intrareservoir pressure and functional parameters using radioisotope renography. Forty-three patients for whom ileal reservoir construction was performed by Kock pouch (n = 33) or Hautmann's ileal neobladder (n = 14) approaches between November 1984 and September 1996 were studied. After the reservoir contents were catheterized, (99m)Tc-MAG 3 renoscintigraphy was carried out and time activity curves in the kidney (renogram) and reservoir (reservoirgram) were recorded, while saline solution was poured into the reservoir for monitoring of intrareservoir pressure. Three basic abnormal curves were noted in the excretory phase on renograms: a normal downward curve followed by an upward curve, a continuous upward curve associated with or without a sharp decline after the catheterization of the reservoir contents, and episodes of spike waves. Based on these curves, renograms were classified into five types: normal, high pressure, retention, obstruction, and reflux. Abnormal types were noted with 51 of 65 renal units (78.5%) in the Kock pouch group and 15 of 25 renal units (60.0%) in the neobladder group. This examination method may be useful for evaluating urodynamics in the upper urinary tract of patients with a continent ileal reservoir and provide data on adequate voiding volumes for the individual patient.

Adult↗