PET/CT in pediatric oncology.

Radionuclide functional imaging has become a central part of pediatric oncological practice. There have been a number of major advances in imaging technology in recent years, but multislice CT with PET is the modality generating most interest in cancer imaging. In this review, we discuss the common uses and specific issues with regard to PET-CT imaging in pediatric practice. Brain tumors form a significant percentage of pediatric oncology. Use of FDG-PET in brain tumors has helped distinguish viable, residual, or recurrent tumor from post-therapeutic changes and necrosis. High-grade tumors show high uptake of FDG at diagnosis. FDG-PET results may also not accurately correlate with tumor progression after intensive radiation therapy. FDG-PET has been applied to accurate biopsy of infiltrative tumors, tumor grading, and prognostication. Limited available data also suggest that FDG-PET findings correlate well with histopathology and clinical outcome in children. FDG uptake is generally greater in higher grade lymphomas than in lower grade lymphomas. FDG-PET reveals disease sites that are not detected by conventional staging methods, resulting in upstaging of disease with potential therapeutic review. FDG-PET is useful for assessing need for marrow biopsy, residual or recurrent soft tissue masses seen on CT after therapy. The primary role of FDG-PET in neuroblastoma is in non-MIBG concentrating tumors. [11C]-Hydroxyephedrine ([11C]-HED), an analogue of norepinephrine, and [11C]-epinephrine PET have also been used in evaluating neuroblastoma. Uptake of these tracers is demonstrated within minutes after tracer administration, an advantage over MIBG imaging. The exact roles of FDG-PET in osteosarcoma and Ewing's sarcoma are not definitive. FDG-PET may play an important role in monitoring response to therapy Another diagnostic role may be in assessing patients with suspected metastatic disease.

Thyroid hormone binding protein abnormalities in patients referred for thyroid disorders.

BACKGROUND & OBJECTIVES: Thyroid hormone binding protein (THBP) abnormalities are the major cause of discordance in commonly performed total thyroxine (T4) and thyrotropin (TSH) estimations, though these do not interfere with thyroid hormone action. Determination of such abnormalities in patients showing discordant thyroid function tests (TFTs) is diagnostically important as it eliminates equivocal assessment of thyroid function and treatment especially where proper methodology for free T4 (FT4) estimation is not available. This study was undertaken to analyse the THBP abnormalities in the population attending thyroid clinic. Family members of affected patients were also screened to study the inheritance of quantitative TBG abnormalities. METHODS: Blood samples of 15000 consecutive patients over a period of 4 years (1994-1997) were tested for thyroid function. THBP abnormalities were studied using polyacrylamide gel electrophoresis autoradiography. Serum thyroxine binding globulin (TBG), free and total T4, total tri-iodothyronine (TT3) were assayed by radioimmunoassay methods. RESULTS: In our screening of 15,000 thyroid patients over a four year period, we found the presence of complete and partial TBG deficiency and TBG excess to be 1:2,500, 1:200 and 1:15,000 respectively. Our study on the families of three affected patients revealed X-chromosome linked inheritance pattern of TBG deficiency in two families and TBG excess in one family. INTERPRETATION & CONCLUSION: Our study suggests that it would be beneficial to rule out THBP abnormalities before interpreting results of TFTs, particularly when there is large discrepancy between T4 and TSH levels. In case of inherited THBP abnormalities, the family members of the affected individual should also be screened to avoid misdiagnosis and erroneous treatment in case they develop thyroid dysfunction in future.

Hepatobiliary clearance of labelled mebrofenin in normal and D-galactosamine HCl-induced hepatitis rats and the protective effect of turmeric extract.

This study was carried out to see the hepatobiliary clearance of 99m Tc-Mebrofenin radiopharmaceutical in D-galactosamine induced hepatic rats. Furthermore, protective effect of turmeric extract has been studied in these hepatitis rats. Hepatitis was induced with intraperitoneal injection of D-galactosamine (400 mg/kg b. wt) in these rats. 1% turmeric extract was given along with their normal diet for 15 days. Turmeric extract treatment significantly increased the hepatic uptake of radioactivity and accelerated the excretion of 99m Tc-Mebrofenin as compared to control rats. (P < 0.001). In D-galactosamine administered rats, a significant delay was observed in 99m Tc-Mebrofenin excretion as compared to controls. However, D-galactosamine administered rats, pretreated with turmeric extract or concurrently treated with turmeric extract showed a near normal pattern of 99m Tc-Mebrofenin excretion. Hence, it can be suggested that turmeric extract may improve the liver function by detoxification.

99mTc-labeled field bean protease inhibitor can function as an efficient tumor detecting agent.

Purified field bean protease inhibitor (FBPI) was labeled with 99mTcO4- to ascertain its ability to locate tumors in tumor-bearing rat models. The labeling was done with Sn2+ as a reducing agent and the yield was 95%. It was stable for 2 hr at ambient temperature. The biodistribution study of the intravenously injected radiolabeled FBPI in normal Wistar rats at various time intervals showed a rapid blood clearance from the systemic circulation (approximately 5hr). The complex was predominantly excreted through the renal and the hepatobiliary systems. In vivo distribution and scintiimaging of 99mTc-FBPI were carried out in rats bearing carcinogen-induced mammary tumor or transplanted C6-gliomas. The results obtained were compared with conventional tumor-seeking radiopharmaceuticals such as 99mTc-(V)dimercaptosuccinic acid (DMSA), 201Thallous chloride (TICI) and 99mTc-Citrate. The tumor to muscle (T/M) ratios obtained with 99mTc-FBPI in rat C6 glioma was nearly 2 to 5-fold higher than obtained with all the three conventional tumor-seeking agents. The T/M ratio obtained with 99mTc-FBPI in rat mammary tumor on the other hand appeared to be 2-3-fold higher than noted with 99mTc(V)-DMSA and 201TlCl. The ratio was however comparable with that obtained with 99mTc-Citrate. The study indicated that 99mTc-FBPI has the specific potentials for imaging gliomas and possibly other tumors as well.

Protective effect of turmeric (Curcuma longa L.) extract on carbon tetrachloride-induced liver damage in rats.

The protective effect of tumeric extract (TE) in diet on CCl4-treated rats was studied. Rats were divided into 5 groups: (1) untreated, (2) CCl4 treated, (3) pre-TE for 2 weeks followed by CCl4, (4) TE + CCl4 given concurrently and (5) 5% TE as positive control. The serum levels of bilirubin, cholesterol, aspartate aminotransferase, (AST), alanine amino transferase (AST), (ALT) and alkaline phosphatase were estimated after 1, 2 and 3 months. CCl4 caused a maximum increase (2-3-fold in all the above parameters. As compared to CCl4 group, a short pre-treatment of TE showed reduction in cholesterol, bilirubin, AST, ALT and alkaline phosphatase activity whereas concurrent treatment of TE + CCl4 reduced to a greater extent the levels of all parameters except ALT. To conclude, concurrent treatment of TE gave significant protection against CCl4 though the values did not reach the normal levels.

131I-MIBG scintigraphy in neural crest tumours.

Radioiodinated meta-iodobenzylguanidine (131I-MIBG) has been widely used for the diagnosis of neuroblastomas, pheochromocytomas, paragangliomas and medullary carcinomas of thyroid. We have developed a procedure for preparation of 131I-MIBG and studied its utility in diagnosis of primary and metastatic neural crest tumours. Studies were carried out in 54 patients. Of them 39 cases were of neuroblastomas, 1 pheochromocytoma; 6 operated medullary carcinomas; 5 paragangliomas; 2 Ewing's sarcoma and 1 Rhabdomyosarcoma; The sensitivity for the detection of primary tumours of neuroblastomas was 94% and for the detection of metastasis was 83%; while in the case of paragangliomas and medullary carcinoma, the sensitivity was 75% and 70% respectively. Our experience in the present study shows that 131I-MIBG scintigraphy is a sensitive and specific diagnostic tool to localise primary and metastatic disease of neural crest tumours.

Iodine deficiency in adolescents from Bombay slums.

BACKGROUND. Iodine deficiency may be associated with endemic goitre, lowered levels of circulating thyroid hormone and suboptimal brain function. We studied iodine deficiency, thyroid status and scholastic performance in 866 (416 girls and 450 boys) adolescents from the slums of Bombay. METHODS. We examined 866 adolescents (416 girls and 450 boys) to determine the presence of goitre. Circulating levels of T3 and T4 were estimated by radioimmunoassay and of thyroid stimulating hormone by the immunoradiometric assay technique. Their scholastic performance was assessed by the average marks obtained in the last examination. RESULTS. The prevalence of goitre was 56% in both boys and girls. The visible goitre rate was also similar in boys (9.8%) and girls (10.6%). We found no significant difference in the mean urinary iodine excretion and urinary iodine to creatinine ratio between boys and girls, but the mean serum T3 and T4 levels were lower in girls than in boys, while the thyroid stimulating hormone levels were higher. The mean thyroid hormone levels were consistent with normal thyroid function. With an increase in the size of goitre, there was a decrease in urinary iodine excretion, urinary iodine to creatinine ratio, T3 and T4 levels while the thyroid stimulating hormone levels increased. The scholastic performance of the adolescents with goitre was poor. Forty-eight per cent of them obtained less than 50% marks and their academic grades showed a significant association with thyroid stimulating hormone levels. CONCLUSION. Goitre has a high prevalence among adolescents in the slums of Bombay. This can be attributed partly to the increasing demand for iodine at puberty which cannot be satisfied with the limited amounts available in food. The children also show a poor scholastic performance. Mild iodine deficiency can be easily controlled by encouraging the use of iodized salt in adolescents.

Bone scans in neuroblastoma.

Eighty-Six patients of neuroblastoma ranging in age from four months to 15 years were studied with 99m Tc-MDP for total skeletal survey over a period of seven years (1983-1990). The diagnosis of neuroblastoma was based on bone marrow examination, FNAC, lymph node biopsy, histopathology. Bone imaging was performed three hrs. after intravenous administration of 99m Tc-MDP. Out of 86 patients, 45 patients had positive bone scan showing osseous concentration in 122 sites and extraosseous concentration in 34 sites. Seven patients had liver metastases. None of these liver metastases showed concentration of MDP. Fourteen patients underwent surgery for the primary tumour at the time of bone scanning. Ten patients were studied at the time of follow up, of which four patients showed good response as bony metastases were not demonstrated on bone scintigraphy and X-rays. In conclusion, bone scan is an useful test in neuroblastoma in delineating the bony metastases and also in assessing the efficacy of chemotherapy in these patients.

T lymphocytes in pulmonary tuberculosis.

T cells and their sub-populations were evaluated with respect to reactive, intermediate and unreactive forms of tuberculosis as classified by Lenzini. Significant CD4 lymphopenia and a reduction of CD4/CD8 ratios were found in patients with reactive tuberculosis. It was observed that there was a B lymphocytosis, CD8 lymphocytosis and a reduction of CD4/CD8 ratio in patients with intermediate and unreactive forms of tuberculosis. The T lymphocytes and CD4 subset were unchanged. There was no significant difference in the lymphocytes and sub-populations among the intermediate and unreactive groups.

Total and free thyroid hormone levels in chronic renal failure.

The levels of serum total thyroxine (TT4), triiodothyronine (TT3), free T3, (FT3) free T4 (FT4) and thyrotropin (TSH) were measured in 127 clinically euthyroid patients with varying grades of chronic renal failure (CRF); and 97 healthy individuals. They were grouped as: Group I containing 93 patients on conservative management; Group II containing 34 patients on regular dialysis therapy; and Group III (normals). Group I patients showed significant decrease in TT3, TT4 and FT3 levels (p less than 0.001) as compared to Group III, whereas FT4 and TSH values in group I were not significantly altered. TT3, TT4 and FT3 levels reduced as the severity of renal damage increased. Variations in TT3, TT4, FT3, FT4 and TSH levels in Group II patients were similar to those in Group I, except for a decrease in TSH levels (p less than 0.05) as compared to normals. Several thyroid function tests are abnormal in CRF patients, however, finding of normal FT4 and TSH levels would indicate functional euthyroid status.

Determination of free thyroxine in serum using column chromatography & radioimmunoassay.

A simple method for measurement of free thyroxine (FT4) levels in serum by adsorption chromatography and subsequent radioimmunoassay (RIA) is described. Assay sensitivity observed by this method was 1.2 pg/ml. Intra-assay variability was 11.2 per cent for FT4 concentrations of 7.9 pg/ml (n = 10), while interassay variability was 23.3, 9.7 and 12.9 per cent respectively for concentrations of 2.66, 12.06 and 23.96 pg/ml (n = 16). Serum FT4 concentration estimated by this method in 79 euthyroid patients was found to be 10.8 +/- 3.1 pg/ml. Values of FT4 obtained in hypothyroid and hyperthyroid patients were outside the normal range. FT4 values obtained by this method correlated well with the standard Liso-phase FT4 kit (r = 0.8) as well as free FT4 index (r = 0.93).

Etiology of childhood hypothyroidism.

This study prospective without any selection bias included 80 of the 152 hypothyroid infants and children seen over the past six years. The clinical diagnosis was confirmed by TSH and thyroid hormone (T3, T4) studies. Scanning for thyroid with TC99m pertechnetate was carried out in all except seven older children with grade II and III goiters where 131I uptake studies were done. Serum thyroglobulin (RIA) was estimated and antithyroglobulin and antimicrosomal antibodies were tested. Based on thyroid 131I scan or 131I uptake, 52.5% had no demonstrable thyroid tissue except one with hypoplasia (Group I, n = 42), 25% had ectopic thyroid (Group II, n = 20), and 22.5% had normal or enlarged thyroid gland (Group III, n = 18). One hypothyroid patient of Group III had thyroiditis with high antibody titre and one was proved to have iodine deficiency). The mean age at time of diagnosis was lowest in Group I (age in months--30.3 +/- 36.2; 60.6 +/- 53.9; 106.2 +/- 69.3 in Groups I, II and III respectively. The intergroup differences in age were significant. The mean serum Tg levels increased progressively from Groups I to III. In the present series thyroid dysgenesis led to hypothyroidism in 77.5%, with athyreosis in 52.5% and ectopia in 25%. Dyshormonogenesis was noted in 20% and thyroiditis in 1.5%.