Flare phenomenon following gefitinib treatment of lung adenocarcinoma with bone metastasis.

The skeleton is the most common site for distant metastasis in patients with cancer. To detect bone metastasis and evaluate the efficacy of treatment, we usually use bone scintigraphy and check serum alkaline phosphatase (ALP). However, such evaluation is sometimes difficult due to flare phenomenon. A 61-year-old male was referred to our department with a suspected diagnosis of lung cancer. Following thorough examinations, he was diagnosed with primary lung cancer (adenocarcinoma, Stage IV) and found to have a mutation in the epidermal growth factor receptor gene at exon 21 (L858R). After initiating treatment with oral gefitinib, ALP increased and peaked at 3,592 U/L by 3 weeks and decreased thereafter. At 4 weeks following treatment initiation, bone scintigraphy revealed a marked increase in abnormal accumulation of (99m)Tc-polyphosphate, but the primary tumor and metastases in regions other than the bone were reduced. At 9 weeks after treatment initiation, abnormal accumulations was improved in bone scintigraphy, and computed tomography revealed osteoblastic changes consistent with the accumulated lesion observed by bone scintigraphy. After initiating cancer treatment for bone metastasis, it is not uncommon to observe transient asynchronous accumulation in bone scintigraphy or transient increases in ALP in patients who ultimately respond to the treatment. These changes are called flare phenomenon, and documented in patients with prostate cancer or breast cancer receiving treatment. When determining the efficacy of treatments that target carcinomas with bone metastases, it is important to note that flare phenomenon is often indistinguishable from disease progression indicators.

Rapid determination of the radiochemical purity of 99mTc-antimony trisulfide colloid prepared by standard and alternative heating methods.

UNLABELLED: The purpose of this study was to validate a rapid quality control method for the lymphoscintigraphic tracer 99mTc-antimony trisulfide colloid (99mTc-ATC). METHODS: ATC was labeled with 99mTc according to the manufacturer's instructions as well as by alternative heating conditions designed to provide a range of percentages of radiochemical purity (RCP): the tracer was prepared in a dry block heater with heating cavities of different sizes, the temperature of the heating block was varied from 70 degrees C to 115 degrees C, or the duration of heating was varied from 15 to 35 min. Anion-exchange minicolumns were trialled to separate any 99mTc-pertechnetate impurity from 99mTc-ATC with physiologic saline as the eluent. Quality control results were compared with the results from the manufacturer's recommended method, which uses an instant thin-layer chromatography (ITLC) strip with saline as the migrating solution. RESULTS: The quality control results obtained with a cartridge method in 2-3 min compared favorably with those obtained with the ITLC method with saline when the tracer was prepared by heating at 115 degrees C in a dry block heater for 35 min (RCPs, 99.4%+/-0.3% [mean+/-SD] and 99.2%+/-0.3%, respectively; n=25). The cartridge and ITLC quality control results also were in excellent agreement (correlation coefficient, 0.99) over a range of RCPs (80%-100%). An alternative anion-exchange cartridge that was tested in this study was not suitable for assaying the RCP of 99mTc-ATC because of the complete retention of 99mTc-pertechnetate on the sorbent. CONCLUSION: Compared with the established ITLC method, the cartridge quality control method tested in this study is rapid and provides a reliable assessment of the RCP of 99mTc-ATC. For the preparation of 99mTc-ATC, a dry block heater can be successfully substituted for a boiling water bath and is recommended for heating at high altitudes.

Evolution of technetium speciation in reducing grout.

Cementitious waste forms (CWFs) are an important component of the strategy to stabilize nuclear waste resulting from plutonium production by the U. S. Department of Energy. Technetium (99Tc) is an abundant fission product of particular concern in CWFs because of the high solubility and mobility of Tc(VII), pertechnetate (TcO4-), the stable form of technetium in aerobic environments. CWFs can more effectively stabilize 99Tc if they contain additives that chemically reduce mobile TcO4- to immobile Tc(IV) species. The 99Tc leach rate of reducing CWFs that contain Tc(IV) is much lower than that for CWFs that contain TcO4-. Previous X-ray absorption fine structure studies showed that Tc(IV) species were oxidized to TcO4- in reducing grout samples prepared on a laboratory scale. Whether the oxidizer was atmospheric O2 or NO3- in the waste simulant was not determined. In actual CWFs, rapid oxidation of Tc(IV) by NO3- would be of concern, whereas oxidation by atmospheric O2 would be of less concern due to the slow diffusion and reaction of O2 with the reducing CWF. To address this uncertainty, two series of reducing grouts were prepared using TcO4- containing waste simulants with and without NO3-. In the first series of samples, referred to as "permeable samples", the TcO4- was completely reduced using Na2S, and the samples were sealed in cuvettes made of polystyrene, which has a relatively large O2 diffusion coefficient. In these samples, all of the technetium was initially present as a Tc(IV) sulfide compound, TcSx, which was characterized by extended X-ray absorption fine structure (EXAFS) spectroscopy. The EXAFS data is consistent with a structure consisting of triangular clusters of Tc(IV) centers linked together through a combination of disulfide and sulfide bridges as in MoS3. From the EXAFS model, the stoichiometry of TcSx is TC3S10, which is presumably the compound generally referred to as "Tc2S7". The TcSX initially present in the permeable samples was steadily oxidized over 4 years. In the second series of samples, called "impermeable samples", the TcO4- was not initially completely reduced, and the groutsamples were sealed in cuvettes made of poly-(methyl methacrylate), which has a small O2 diffusion coefficient. In the impermeable samples, the remaining TcO4- continued to be reduced, presumably by blast furnace slag in the grout, as the samples aged. When the impermeable samples were opened and exposed to atmosphere, the lower-valent technetium species were rapidly oxidized to TcO4-.

Radiolabelling of egg meals for gastric emptying studies: a comparison of 99mTc sulfur and 99mTc stannous colloids.

OBJECTIVES: To establish whether 99mTc stannous (Tc-Sn) colloid is a suitable alternative to 99mTc sulfur (Tc-S) colloid for gastrointestinal studies, we compared the per cent binding to egg solids (%BS) and radiochemical purity (RCP) of both colloids in digesting media. METHODS: Egg white and yolk containing colloids were cooked separately and mashed. Samples of 4-5 g were digested over 2-3 h (37 degrees C) in excess simulated gastric juice (SGJ: 15 ml of 0.1 M HCl and 0.5 g.l-1 pepsin) or water, centrifuged, imaged with a gamma camera and the %BS computed. RCP was determined in aspirates taken from these preparations and from solutions of colloid added directly to SGJ. RESULTS: The %BS in egg white after 3 h in SGJ for both colloids were similar: Tc-Sn, 62+/-8 (n=12); Tc-S, 61+/-6 (n=8), but markedly lower than 95% (the often quoted literature value). Egg yolk was digested more rapidly than egg white: %BS after 2 h in SGJ for Tc-Sn colloid was 55+/-10 (n=5) in the yolk, compared to 77+/-4 (n=5) in the white (P<0.01). The RCP for Tc-S colloid alone in SGJ was >94% over 3 h but for Tc-Sn colloid was as low as 14%. For egg white, the RCP in SGJ was 91-96% for Tc-S and 80-91% for Tc-Sn. For egg yolk the RCPs in SGJ were similar for both colloids (>90%). The RCP in water digesting egg white or yolk containing either colloid was always lower than in the corresponding SGJ aspirates, indicating a leakage of small amounts of non-colloidal 99mTc. CONCLUSIONS: Although 99mTc-Sn almost completely dissociates in SGJ, once cooked in egg it is digested similarly to 99mTc-S. Variations in the size of digesting egg fragments and in SGJ composition can reconcile the lower %BS values obtained with previously reported higher results. 99mTc-Sn colloid cooked in egg appears suitable for gastrointestinal studies.

Electrospray mass spectrometry of a series of mixed nitrido 99gTc- heterocomplexes conjugated with bioactive molecules.

Electrospray ionization mass spectrometry (ESI-MS) was successfully employed for the identification of six nitrido technetium mixed ligand complexes with a general formula of [99gTc(N)(O,S-BID)(PNP)], where PNP represents a heterodiphosphine and O,S-BID represents a simple dianionic bidentate ligand (compounds 1-3) or a more sophisticated N-substituted O,S-cysteine framework conjugated with a bio- active molecule (BAM) (compounds 4-6). In spite of similar coordination spheres exhibited by all the complexes investigated, simple co-ordination compounds 1-3 displayed collisionally-induced fragmentation processes (MSn) different from those observed in biomolecule-containing compounds 4-6. In the latter, more decomposition channels were observed. This behavior is likely to be associated with some additional intramolecular contacts of the biomolecule (or part of the biomolecule) with pendant group(s) incorporated in the PNP-co-ligand. This view is further supported by the observations arising from both in vitro binding affinity experiments and nuclear magnetic resonance investigations. The presence of cationized forms for all compounds 1-6 and the practical lack of the [2M + Na]+ species for biomolecule-containing compounds 4-6 provided further evidence of a subtly different structural conformation.

[The stability of solid food labeled with different radiopharmaceuticals for studying gastric emptying]. / Estabilidad de alimento sólido marcado con diferentes radiofármacos para vaciamiento gástrico.

OBJECTIVE: Sulfur colloid 99mTc-SC, the radiopharmaceutical of choice for solid gastric emptying studies, is not available in our country. It has led us to assess the solid binding stability of seven alternative radiopharmaceuticals that could present adequate fixation to it a priori. MATERIALS AND METHOD: The stability of labelled solid food with seven colloidal 99mTc-radiopharmaceuticals of different sizes and nature (MAA, tin colloid, rhenium sulphide macrocolloid, albumin microcolloid, sulfur nanocolloid, albumin nanocolloid and rhenium sulfur nanocolloid) has been studied by measuring their dissociated activity after two hours digestion in simulated gastric fluid (kept 120' in agitation, in HCl 0.1 M at 37). The survey also assesses radiopharmaceutical labelling stability after two hours digestion in identical conditions by measuring their radiochemical purity in ITLC. RESULTS: In these conditions, MAA, rhenium sulphide macrocolloid, albumin microcolloid and albumin microcolloid present the best behaviour, with an activity linked to food over 90 % of the previously fixed activity. CONCLUSIONS: According to the results, there is no relationship between the radiopharmaceutical size and nature and the stability of its binding to the solid food. Because rhenium sulphide macrocolloid is no longer manufactured and the other three radiopharmaceuticals which have a binding stability to the solid food over 90 % do not include digestive explorations amongst their indications, nowadays, there is a serious legal limitation to carry out this type of studies in our country.

Failure to remove true sentinel nodes can cause failure of the sentinel node biopsy technique: evidence from antimony concentrations in false-negative sentinel nodes from melanoma patients.

We have recently found that antimony (originating from the technetium 99m antimony trisulfide colloid, used for preoperative lymphoscintigraphy) can be measured in tissue sections from archival paraffin blocks of sentinel nodes (SNs) by means of inductively coupled plasma mass spectrometry (ICP-MS) to confirm that removed nodes are true SNs. We performed a retrospective analysis of antimony concentrations in all our false-negative (FN) SNs to determine whether errors in lymphadenectomy (i.e., failure to remove true SNs) may be a cause of FN SN biopsies (SNBs). Among 27 patients with an FN SNB, metastases were found on histopathologic review of the original slides or additional sections in 7 of 23 patients for which they were available; however, antimony concentrations were low in 5 of 20 presumptive SNs. Our results suggest that an FN SNB can occur because of failure to remove the true SN as well as histopathologic misdiagnosis.

Identification of the non-pertechnetate species in Hanford waste tanks, Tc(I)--carbonyl complexes.

Immobilization of the high-level nuclear waste stored at the Hanford Reservation has been complicated by the presence of soluble, lower-valent technetium species. Previous work by Schroeder and Blanchard has shown that these species cannot be removed by ion-exchange and are difficult to oxidize. The Tc K-edge XANES spectra of the species in Tanks SY-101 and SY-103 were reported by Blanchard, but they could not be assigned to any known technetium complex. We report that the XANES spectra are most likely those of Tc(I)-carbonyl species, especially fac-Tc(CO)3(gluconate)(2-). This is further supported by EXAFS and 99Tc-NMR studies in nonradioactive simulants of these tank wastes.

Is technetium-99 (Tc-99) radiologically significant?

According to radiological protection authorities the radioisotope technetium-99 (Tc-99) is not 'radiologically significant' to humans or other species. The Sellafield plutonium reprocessing plant discharges large amounts of Tc-99 into the Irish Sea; by the year 2015 a total of about 3,000 tera-becquerels of Tc-99, weighing about 5 tonnes, will have been discharged. This article considers the effects of Tc-99 on the environment. After discharge, Tc-99 travels large distances in the ocean. Levels of Tc-99 in Norwegian coastal waters increased by ten times between 1991 and 1996. Tc-99 becomes concentrated offshore in seaweed, winkles and mussels. A concentration factor of 120,000 has been reported in seaweed and one of 650,000 has been measured in the green gland of lobster. It may be necessary to reassess the risk to human health following the ingestion of the relevant isotopes, including Tc-99, because of the possibility of radiation induced genomic instability, as well as the cancer risk. The committed effective doses used to determine permitted levels of intake of these isotopes should be increased and the authorized limits for the discharge of radioactive wastes from Sellafield reduced. Authorized limits of the discharge of radioactivity should be based on Contaminated Food Intervention Levels rather than Generalized Derived Limits as they are now.

A rapid chromatographic method for quality control of technetium-99m-bicisate.

UNLABELLED: The purpose of this work was to develop a simple and rapid method to determine the radiochemical purity of 99mTc-bicisate. METHODS: A rapid paper chromatographic (PC) method was developed to determine the radiochemical purity of 99mTc-bicisate and compare the results with those of the manufacturer's recommended method. The present PC method included Whatman 3MM paper as the solid phase and ethyl acetate as the solvent. RESULTS: The time for chromatography by this technique was 4-5 min compared to about 23 min by the manufacturer's method. The Rf value of 99mTc-bicisate (Rf = 0.9-1.0) was widely different from those of 99mTcO4- and reduced 99mTc (Rf = 0.0 for both) so the chromatographic strip after development could be readily cut into two segments, in order to determine the labeling yield. CONCLUSION: No significant difference in labeling yields was found between the present method and the manufacturer's method. The PC method using Whatman 3MM paper and ethyl acetate is a simple and fast technique to determine the radiochemical purity of 99mTc-bicisate and may be substituted for the manufacturer's recommended method to save time.