Clinical impact of whole-body FDG-PET for evaluation of response and therapeutic decision-making of primary lymphoma of bone.
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Biomedical subjects
Publications and source records attributed to S M Lim.
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We have developed an efficient method and an automated synthetic system for the preparation of highly concentrated 188Re-MAG3. Routine production of 188Re-MAG3 for use in intracoronary radiation therapy was performed by compressed air driven semi-automated shielded system. 188Re-MAG3 was prepared with a commercial kit and reducing agents, purified and concentrated by C18 Sep-Pak cartridges to desired radioactivity and volume. Using this automated system, reproducible radiolabeling yields of 80-85% were obtained.
A samarium 153-chitosan complex was prepared by simply mixing acidic solutions of chitosan and (153)SmCl(3). When a solution of this complex was injected into the knee joints of rabbits, minimal extra-articular leakage was observed. This can be attributed to the rapid change in the pH of the complex solution from acidic to neutral, resulting in the formation of gel followed by the subsequent retention in the administered site. Thus, the complex solution represents a promising candidate for radiation synovectomy.
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We present three patients with Nasopharyngeal Carcinoma (NPC) developing swallowing problems after radiotherapy as the primary modality of treatment. All patients had advanced stage NPC presenting with enlarged neck nodes and underwent radical external beam radiotherapy. All three patients had both CN X and CN XII palsies and had difficulty in both the oral and pharyngeal phases of swallowing. None of them has any clinical or radiological evidence of local recurrence in the post nasal space and neck or metastasis to the skull base. One patient underwent cricopharyngeal myotomy with epiglottopexy and hyoid suspension which failed and subsequently underwent laryngectomy. Another patient had medialisation thyroplasty and the third underwent a percutaneous endoscopic gastrostomy (PEG).
Degeneration of both motoneurons and interneurons has been previously observed in amyotrophic lateral sclerosis. It is unclear whether interneuronal loss is due to an intrinsic neuronal defect or if it occurs secondary to loss of their target motoneurons. We have examined the target dependence of interneurons, their survival and alterations in the expression of the calcium binding protein, calbindin-D28k (CB), in the ventral horn of the rat lumbar cord after extensive motoneuron degeneration was induced by unilateral rhizotomy of spinal nerves L2-L6 at postnatal day 3 (P3). Counts of Nissl-stained cells at P21 revealed no significant interneuronal death despite loss of 80% of their target motoneurons. At P6, some motoneurons transiently expressed CB on the operated side compared to the control side. Since most of these cells are destined to die, this transiently increased CB expression may represent an abortive attempt by the axotomised motoneurons to buffer the neurotoxic consequences of high intracellular calcium. In contrast, there was a time-dependent decrease in CB expression in ventral horn interneurons, with only 35% of putative Renshaw cells expressing CB by P21. These results indicate that neonatal interneurons are capable of surviving the loss of their motoneuron targets, but alter their phenotype as indicated by functional alterations in calcium-binding proteins.
Oka strain VR-795 (Varicella Zoster Virus, VZV) of American Type Culture Collection (ATCC) has been used for chickenpox vaccine production. In order to use this strain for vaccine production, the strain must be identified and its stability must be confirmed. The identification of the Oka strain has been confirmed using Restriction Fragment Length Polymorphism (RFLP) and DNA sequence analysis of glycoprotein-II (gp-II). The amino acid sequences of Oka deduced from the DNA sequence of gp-II have changed at three amino acids against Ellen and at one amino acid against Webster. To prove the stability of the Oka strain during the passage, RFLP and DNA sequence analyses were also used with 11, 15 and 23 times of virus passage. We found that the Oka strain was stable at passages of up to 23 times, based on the RFLP and DNA sequence analyses. The confirmed Oka strain was renamed as BR-Oka for the purposes of chickenpox vaccine production.
AIMS: The purpose of this study was to describe the population pharmacokinetics of intravenous and oral tacrolimus (FK506) in 20 Asian paediatric patients, aged 1-14 years, following liver transplantation and to identify possible relationships between clinical covariates and population parameter estimates. METHODS: Details of drug dosage histories, sampling times and concentrations were collected retrospectively from routine therapeutic drug monitoring data accumulated for at least 4 days after surgery. Before analysis, patients were randomly allocated to either the population data set (n = 16) or a validation data set (n = 4). The population data set was comprised of 771 concentration measurements of patients admitted over the last 3 years. Population modelling using the nonlinear mixed-effects model (NONMEM) program was performed on the population data set, using a one-compartment model with first-order absorption and elimination. Population average parameter estimates of clearance (CL), volume of distribution (V) and oral bioavailability (F) were sought; a number of clinical and demographic variables were tested for their influence on these parameters. RESULTS: The final optimal population models related clearance to age, volume of distribution to body surface area and bioavailability to body weight and total bilirubin concentration. Predictive performance of this model evaluated using the validation data set, which comprised 86 concentrations, showed insignificant bias between observed and model-predicted blood tacrolimus concentrations. A final analysis performed in all 20 patients identified the following relationships: CL (l h-1) = 1.46 *[1 + 0. 339 * (AGE (years) -2.25)]; V (l) = 39.1 *[1 + 4.57 * (BSA (m2)-0. 49)]; F = 0.197 *[1 + 0.0887 * (WT (kg) -11.4)] and F = 0.197 *[1 + 0.0887 * (WT (kg) -11.4)] * [1.61], if the total bilirubin > or = 200 micromol l-1. The interpatient variabilities (CV%) in CL, V and F were 33.5%, 33.0% and 24.1%, respectively. The intrapatient variability (s.d.) among observed and model-predicted blood concentrations was 5.79 ng ml-1. CONCLUSIONS: In this study, the estimates of the pharmacokinetic parameters of tacrolimus agreed with those obtained from conventional pharmacokinetic studies. It also identified significant relationships in Asian paediatric liver transplant patients between the pharmacokinetics of tacrolimus and developmental characteristics of the patients.
BACKGROUND AND OBJECTIVES: The rare MNS antigen Or (MNS31) is sensitive to ficin, papain and sialidase, but partially resistant to trypsin (0.05%); the effect of alpha-chymotrypsin is not known. A point mutation, 204C --> T in exon 3 of GYPA, is associated with the Or+ phenotype. We report here the first case of hemolytic disease of the newborn (HDN) caused by anti-Or, and expand the information on the nature of the Or determinant. MATERIALS AND METHODS: A woman, gravida 4, para 0, delivered a baby whose red blood cells (RBCs) were positive (2+) on the direct antiglobulin test (DAT). The mother's serum, an eluate made from the baby's RBCs and the RBCs of the baby's father were investigated. Exon 3 of GYPA, extracted from the father's genomic DNA, was amplified and sequenced. RESULTS: The mother's serum reacted at room temperature, 37 degrees C and on the indirect antiglobulin test with RBCs from the baby's father. The father's RBCs were M+N+S-s+Or+. The antibody in the mother's serum and in the baby's eluate was identified as anti-Or. The serum did not react with the father's RBCs treated with trypsin (180,000 U/ml), but did react with his alpha-chymotrypsin-treated RBCs. Amplification and sequencing of DNA from the father revealed a single point mutation, 204C --> T, in GYPA exon 3. At birth, the baby had clinical symptoms of HDN and was transfused with 36 ml of packed RBCs and received phototherapy for eight days. At week 11, the baby's M+N+S+s+Or+ RBCs were negative on the DAT. CONCLUSION: This is the first case of HDN caused by anti-Or. The observed point mutation, 204C --> T, confirms that of a previous report and predicts a change of Arg (Or-) to Trp (Or+) at amino acid 31.
OBJECTIVE: We evaluate the efficacy and safety of sonographically guided ethanol sclerotherapy for benign thyroid cysts. SUBJECTS AND METHODS: We examined 22 patients with benign thyroid cysts (13 complex cysts and nine pure cysts) confirmed by fine-needle aspiration biopsy. Sonographically guided aspiration of the cystic fluid was followed by instillation of absolute ethanol (99.9%) into the cystic cavity: the injected volume of ethanol was 40-100% of the volume of fluid aspirated. The procedure was performed every 1 or 3 months for one or two sessions (mean, 1.2 sessions). Follow-up sonography was performed 1-10 months after the final session, and we observed patients after ethanol sclerotherapy for complications. RESULTS: The initial volume of the cysts ranged from 3.5 to 42 ml. In 21 patients, the volume of the cyst decreased or the cyst was obliterated. The volume of the cyst was reduced by 50-99% in 13 patients and by 1-49% in six patients, and the cyst was obliterated in two patients. In one patient, the volume of the cyst increased. The volume of ethanol instilled was significantly correlated with the volume reduction rate of the cyst. There was a difference in the volume reduction rate between patients in whom 10 ml or more of initial volume was used and those in whom less than 10 ml of initial volume was used; that is, the volume reduction rate of the group with the initial cyst volume of more than 10 ml was higher than that of the other group. Important long-standing and severe complications were not observed. CONCLUSION: Sonographically guided ethanol sclerotherapy is a safe and effective tool for the therapy of benign thyroid cysts.
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UNLABELLED: The management of metastatic thyroid carcinoma patients with a negative 131I scan presents considerable problems. Fifty-four athyrotic papillary thyroid carcinoma patients whose 1311 whole-body scans were negative underwent 18F-fluorodeoxyglucose (FDG) PET; the purpose was to determine whether this procedure could localize metastatic sites. We also assessed its usefulness in the management of these patients. METHODS: Whole-body emission scan was performed 60 min after the injection of 370-555 MBq 18F-FDG, and additional regional attenuation-corrected scans were obtained. Metastasis was pathologically confirmed in 12 patients and was confirmed in other patients by overall clinical evaluation of the findings of other imaging studies and of the subsequent clinical course. RESULTS: In 33 patients, tumor had metastasized, whereas 21 patients were in remission. FDG PET revealed metastases in 31 patients (sensitivity 93.9%), whereas thyroglobulin levels were elevated in 18 patients (sensitivity 54.5%). FDG PET was positive in 14 of 15 metastatic cancer patients with normal thyroglobulin levels. In 20 of 21 patients in remission, FDG PET was negative (specificity 95.2%), whereas thyroglobulin levels were normal in 16 patients (specificity 76.1%). The sensitivity and specificity of FDG PET were significantly higher than those of serum thyroglobulin. In patients with negative 1311 scans, FDG PET detected cervical lymph node metastasis in 87.9%, lung metastasis in 27.3%, mediastinal metastasis in 33.3% and bone metastasis in 9.1%. In contrast, among 117 patients with 131I scan-positive functional metastases, 131I scan detected cervical lymph node metastasis in 61.5%, lung metastasis in 56.4%, mediastinal metastasis in 22.2% and bone metastasis in 16.2%. In all 5 patients in whom thyroglobulin was false-negative with negative antithyroglobulin antibody, PET showed increased 18F-FDG uptake in cervical lymph nodes, mediastinal lymph nodes, or both. Among patients with increased 18F-FDG uptake only in the cervical lymph nodes, the nodes were dissected in 11. Metastasis was confirmed in all, even in normal-sized lymph nodes. CONCLUSION: FDG PET scan localized metastatic sites in 131I scan-negative thyroid carcinoma patients with high accuracy. In particular, it was superior to 131I whole-body scan and serum thyroglobulin measurement for detecting metastases to cervical lymph nodes. FDG PET was helpful for determining the surgical management of these patients.
99mTc complex of hexamethylpropylene amine oxime (99mTc-HMPAO), which has been used as a tracer for regional cerebral blood flow (rCBF), has been shown to localize in primary brain tumors with wide spectrum of its uptake. The causes of the wide spectrum of tumor uptake, however, has not been understood in detail. We performed autoradiographic study with this agent to get further knowledge about HMPAO distribution in 10 cases of transplanted rat gliomas. Eight cases of rat gliomas without tumor necrosis, showed decreased uptake of 99mTc-HMPAO in the autoradiography (average tumor/normal (T/N) uptake ratio: 0.75, range: 0.40-0.90). On the other hand, two cases with tumor necrosis revealed increased uptakes of this agent in central necrotic area. T/N uptake ratios of these two cases were 1.23 and 1.42, respectively. In addition, three patients with histologically proven glioblastoma with tumor necrosis were studied after administration of 20mCi 99mTc-HMPAO. Two out of three patients showed higher uptake of 99mTc-HMPAO in tumor necrotic area than the contralateral area. Our findings suggest that the necrotic area of brain tumor may retain 99mTc-HMPAO and causes an increased uptake.
BACKGROUND: The severity of myelotoxicity after radioimmunotherapy has been predicted from body and blood radiation doses to marrow. However, marrow radiation can be increased substantially if the marrow or skeleton contains the malignancy targeted by the radiolabeled monoclonal antibodies. A study of 29 patients treated with iodine-131 (131I)-Lym-1 showed that radiation doses to marrow from body and blood had little correlation with myelotoxicity. The purpose of the present study was to assess the significance of marrow targeting and other factors for prediction of myelotoxicity. METHODS: Injected radioactivity and nontargeted radiation doses to marrow were compared with peripheral blood cell counts after the first therapy dose of 131I-Lym-1 in 16 heavily pretreated patients with non-Hodgkin's lymphoma (NHL). Bone marrow biopsy, targeted marrow radiation doses, marrow image uptake scores, age, Karnofsky performance score (KPS), previous chemotherapy, and tumor burden were also compared with blood counts. RESULTS: Myelotoxicity was not predicted well by injected radioactivity, total body radiation, or body and blood radiation doses contributed to marrow (P > 0.1). Biopsy-proven bone marrow lymphoma also failed to predict myelotoxicity (P > 0.1). Thrombocytopenia and leukopenia were predicted well by targeted radiation dose to marrow (P < 0.05) obtained by 131I imaging. Similarly, marrow image scores predicted decreases in platelets and white blood cells (WBCs; P < 0.05). Prediction of myelotoxicity using marrow radiation dose methods was slightly improved when serum lactic dehydrogenase (LDH), age, KPS, and prior chemotherapy were included in the analysis (P < or = 0.01). CONCLUSIONS: Prediction of myelotoxicity was improved in this group of patients by assessment of the targeting component of marrow radiation and was better predicted and obtained more easily by semiquantitative marrow image scores. Further improvement in prediction was slight when other factors were considered.
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UNLABELLED: Bone marrow is generally the dose-limiting organ in radioimmunotherapy (RIT). Although radiation doses to marrow estimated from tracer doses have been shown to be comparable to those from therapy doses of radionuclide, the correlation of marrow radiation dose and myelotoxicity has not been well documented. The purpose of this study was to evaluate the relationship between radiation dose to marrow and subsequent changes in peripheral blood cell counts. METHODS: Radiation doses to marrow from three sources, body, blood and marrow targeting, were compared with changes in blood counts after the first therapy dose of (131)I-Lym-1 in 16 patients. Doses of (131)I-Lym-1 ranged from 1.1-8.2 GBq (29-222 mCi). Cumulated radioactivity in the body and marrow were obtained using sequential, quantitative images of the body and lumbar vertebrae, respectively, and that in blood using activity in blood samples. The individual and sum of radiation doses from penetrating radiations in the body, and nonpenetrating radiations in the blood and marrow, were compared with blood counts. RESULTS: In this group of patients, median radiation doses were 15.1, 15.4 and 42.1 cGy from body, blood and marrow targeting, respectively. Linear regression of radiation doses from body and blood versus fractional decreases in blood counts produced correlation coefficients of 0.38, 0.06, 0.22 and less than 0.01 for platelets, granulocytes, white blood cells (WBCs) and hematocrit, respectively. Linear regression of targeted marrow radiation doses versus fractional decreases in blood counts produced correlation coefficients 0.61, 0.31, 0.54 and 0.20 for platelets, granulocytes, WBCs and hematocrit. The closest association was found between radiation dose to marrow from marrow targeting and change in platelet count (r = 0.61). CONCLUSION: In patients, such as those with non-Hodgkin's lymphoma (NHL), likely to have marrow targeting, prediction of myelotoxicity by conventional body and blood contributions to marrow is substantially improved by the use of radiation dose to marrow estimated from images.
We measured the concentration and distribution of tumor associated antigens, TAG-72 and CEA, in stomach cancer by in vitro quantitative autoradiography (IV-QAR). Frozen sections of 33 specimens were incubated with varying concentrations of 125I-labeled CEA-79.1 and B72.3 antibodies specific for carcinoembryonic antigen (CEA) and tumor-associated glycoprotein-72 (TAG-72), respectively. Computer analysis of specific antibody binding gave maximal binding values which were equal to the concentrations of the antigen or epitope. TAG-72 was detected in 25 specimens, at a concentration ranging from 8.4 to 562.9 pmol/g. CEA was detected in 32 of the 33 specimens and its concentration ranged from 8.8 to 525.3 pmol/g. The distribution of TAG-72 by IV-QAR coincided with that of the tumor cells in 41.4% of the pathologic lesions. The distribution of CEA coincided with the tumor cells in 80.5% of pathologic lesions, nearly twice the TAG-72. The concentration of TAG-72 was significantly higher in mucinous adenocarcinoma and mucin containing adenocarcinomas than other types of adenocarcinomas. There was no significant difference in the concentration of CEA among the pathologic types of stomach cancer. In summary, stomach cancer exhibited wide variations in TAG-72 and CEA expression. CEA expression was more frequent and homogeneous than TAG-72.
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