Radioprotection of salivary glands by amifostine in high-dose radioiodine treatment. Results of a double-blinded, placebo-controlled study in patients with differentiated thyroid cancer.

BACKGROUND AND PURPOSE: Parenchymal impairment of salivary glands following high-dose radioiodine treatment is a well-known side effect in general caused by free radicals. Therefore, the radioprotective effect of the radical scavenger amifostine was evaluated prospectively in patients receiving high-dose radioiodine treatment. PATIENTS AND METHODS: Parenchymal function was assessed by quantitative salivary gland scintigraphy performed in 50 patients with differentiated thyroid cancer prior to and 3 months after high-dose radioiodine treatment with either 3 GBq 131I (n = 21) or 6 GBq 131I (n = 29) in a double-blinded, placebo-controlled study. Twenty-five patients treated with 500 mg/m2 amifostine intravenously prior to high-dose radioiodine treatment were compared to 25 control patients receiving physiological saline solution. Xerostomia was graded according to WHO-criteria. RESULTS: In 25 control patients high-dose radioiodine treatment significantly (p < 0.001) reduced parenchymal function of parotid and submandibular glands by 40.2 +/- 14.1% and 39.9 +/- 15.3%, respectively. Nine out of these 25 patients developed Grade I and 2 Grade II xerostomia. In contrast, in 25 amifostine-treated patients there was no significant (p = 0.691) decrease in parenchymal function following high-dose radioiodine treatment, and xerostomia did not occur in any of them. CONCLUSION: Parenchymal damage of salivary glands induced by high-dose radioiodine treatment can be significantly reduced by amifostine which may improve quality of life of patients with differentiated thyroid cancer.

Radioprotection of salivary glands by S-2-(3-aminopropylamino)-ethylphosphorothioic (amifostine) obtained in a rabbit animal model.

BACKGROUND: Impairment of salivary gland function following high-dose radioiodine treatment (HDRIT) is a well-recognized side effect of the treatment. Because differentiated thyroid cancer has an excellent prognosis, reduction of long-term side-effects is mandatory. Therefore, the aim of this study was to investigate the radioprotective effect of amifostine in a rabbit animal model. METHODS: Salivary gland scintigraphy was performed in a total of 16 New Zealand White rabbits. Uptake of 99-Tc-pertechnetate was calculated in percentage of injected activity as a quantitative measure of both salivary gland and thyroid function. Reproducibility of salivary gland scintigraphy was evaluated in one rabbit without any intervention. Fifteen rabbits were studied prior to and up to 6 months after high-dose radioiodine treatment applying 2 GBq 131I. Ten animals received 200 mg/kg amifostine prior to high-dose radioiodine therapy, and 5 served as controls. Salivary glands were examined histopathologically. RESULTS: Variation coefficient of parenchymal function was less than 3.8% in salivary glands. Prior to HDRIT, thyroid uptake was 0.417+/-0.373% and 0.421+/-0.241% in control and amifostine-treated rabbits, respectively. Four weeks after HDRIT, complete ablation of the thyroid was achieved in both groups. Prior to HDRIT, uptake of 99mTc-pertechnetate in salivary glands of five control rabbits was not significantly different from ten amifostine-treated rabbits. In control rabbits 6 months after HDRIT, parenchymal function was reduced significantly (p < 0.0001) by 75.3+/-5.3% and 53.6+/-17.4% in parotid and submandibular glands, respectively. In contrast, in amifostine-treated rabbits, parenchymal function was reduced by 10.6+/-3.4% and 6.5+/-4.3% (p > 0.05) in parotid and submandibular glands, respectively. Histopathologically, marked lipomatosis was observed in control animals but was negligible in amifostine-treated animals. CONCLUSION: Parenchymal damage in salivary glands induced by high-dose radioiodine treatment can be significantly reduced by amifostine in this rabbit animal model. This corresponds to data obtained in patients with differentiated thyroid cancer.

Predictive value of serum S100B for monitoring patients with metastatic melanoma during chemotherapy and/or immunotherapy.

In the immunohistology of malignant melanoma the use of polyclonal antibodies against protein S100 is well established. Recently, it was shown that S100B, a subunit of the S100 protein family, is detectable in the serum of melanoma patients and correlates with the stage of the disease in patients with metastatic melanoma. In the present study, the first evaluation of a large number of treatment observations (n = 77) in 64 different patients during chemotherapy and/or immunotherapy for advanced metastatic melanoma (stage IV) is presented. All patients received treatment according to standardized protocols comprising 8 weeks of treatment followed by routine staging procedures to evaluate therapeutic outcome. In 13 patients with tumour enlargement after first-line therapy, a second-line treatment was subsequently given. S100B immunoradiometric assay (IRMA) tests were performed before, during and after treatment at scheduled time points. In the interim analysis at 4 weeks 29 of 37 (78%) patients with tumour progression during treatment showed a raised S100B level. In the final analysis at 8 weeks, 31 of these 37 patients (84%) demonstrated rising S100B values (P < 0.001). Patients who responded to treatment (stable or regressing metastatic disease) showed constant or declining S100B levels in 38 of 40 patients (95%) at the interim analysis, at 8 weeks this was further increased to 39 of 40 patients (98%; P < 0.001). Thus, the use of S100B for monitoring treatment is adequate in the majority of cases. Our observations are of great interest for therapeutic trials of adjuvant and palliative therapies as the rise of S100B levels might indicate that re-staging and/or changes in therapy strategies should be chosen.

Salivary gland protection by amifostine in high-dose radioiodine therapy of differentiated thyroid cancer.

BACKGROUND: Salivary gland impairment following high-dose radioiodine treatment is a well-recognized side effect, in general caused by free radicals. Therefore, it seemed promising to evaluate the radioprotective effect of the radical scavenger amifostine in patients receiving high-dose radioiodine therapy. PATIENTS AND METHOD: Quantitative salivary gland scintigraphy using 100 to 120 MBq Tc-99m-pertechnetate was performed in 17 patients with differentiated thyroid cancer prior to and 3 months after radioiodine treatment with 6 GBq I-131. Eight patients were treated with 500 mg/m2 amifostine prior to high-dose radioiodine treatment and compared retrospectively with 9 control patients. Xerostomia was graded according to WHO criteria. RESULTS: In 9 control patients high-dose radioiodine treatment significantly (p < 0.01) reduced Tc-99m-pertechnetate uptake by 35.4 +/- 22.0% and 31.7 +/- 21.1% in parotid and submandibular glands, respectively. Of these 9 patients, 3 exhibited xerostomia Grade I (WHO). In contrast, in 8 amifostine-treated patients, there was no significant (p = 0.878) decrease in parenchymal function following high-dose radioiodine treatment, and xerostomia did not occur in any of them. CONCLUSION: Parenchymal damage in salivary glands induced by high-dose radioiodine treatment can be reduced significantly by amifostine. This may help to increase patients' quality of life in differentiated thyroid cancer.

Salivary gland protection by amifostine in high-dose radioiodine treatment: results of a double-blind placebo-controlled study.

PURPOSE: Salivary gland impairment is a well-recognized side effect following high-dose radioiodine treatment (HD-RIT). Since differentiated thyroid cancer has a good prognosis, reduction of long-term side effects is important. Therefore, the effect of amifostine was studied in HD-RIT. PATIENTS AND METHODS: Parenchymal function was assessed by quantitative salivary gland scintigraphy performed prospectively in 50 patients with differentiated thyroid cancer before and 3 months after HD-RIT with either 3 GBq iodine ((131)I) (n=21) or 6 GBq (131)I (n=29) in a double-blind, placebo-controlled study. Twenty-five patients were treated with 500 mg/m2 amifostine intravenously before HD-RIT and 25 patients served as controls, who received physiologic saline solution. Xerostomia was graded according to World Health Organization (WHO) criteria. RESULTS: Before HD-RIT in 25 control patients, uptake of technetium-99m (99mTc)-pertechnetate was 0.45%+/-0.16% and 0.42%+/-0.16% in parotid and submandibular glands, respectively. Three months after HD-RIT, parenchymal function was significantly (P < .001) reduced by 40.2%+/-14.1% and 39.9%+/-15.3% in parotid and submandibular glands, respectively. Nine control patients developed grade I and two grade II xerostomia. In 25 amifostine-treated patients, uptake of 99mTc-pertechnetate was 0.46%+/-0.16% and 0.43%+/-0.17% in parotid and submandibular glands, respectively. Three months after HD-RIT, parenchymal function of salivary glands was not significantly altered (P=.691) and xerostomia did not occur in any of these patients. CONCLUSION: Parenchymal damage in salivary glands caused by HD-RIT can significantly be reduced by amifostine, which may improve the quality of life of patients with differentiated thyroid cancer.

Radioprotection of salivary glands by amifostine in high-dose radioiodine therapy.

UNLABELLED: Salivary gland impairment after high-dose radioiodine treatment is well recognized. Because differentiated thyroid cancer has a good prognosis, reduction of long-term side effects is important. This study investigated the radioprotective effects of amifostine in animals and humans receiving high-dose radioiodine therapy. METHODS: Quantitative salivary gland scintigraphy was performed in five rabbits before and up to 3 mo after high-dose radioiodine therapy applying 1 GBq 131I. Three animals received 200 mg/kg amifostine before high-dose radioiodine therapy, and two served as controls. All animals were examined histopathologically. Quantitative salivary gland scintigraphy also was performed in 17 patients with differentiated thyroid cancer before and 3 mo after high-dose radioiodine therapy with 6 GBq 131I. Eight patients were treated with 500 mg/m2 amifostine before high-dose radioiodine therapy, and nine served as controls. RESULTS: In two control rabbits, high-dose radioiodine therapy significantly reduced parenchymal function by 63% and 46% in parotid and submandibular glands, respectively. In contrast, there was no significant decrease in parenchymal function in amifostine-treated animals. Histopathologically, lipomatosis was observed in control animals but was negligible in amifostine-treated animals. Similar findings were observed in differentiated thyroid cancer patients. In nine control patients, high-dose radioiodine therapy significantly (p < 0.01) reduced parenchymal function by 37% and 31% in parotid and submandibular glands, respectively. Three patients exhibited Grade I (World Health Organization) xerostomia. In contrast, there was no significant decrease in parenchymal function in amifostine-treated patients and no incidence of xerostomia. CONCLUSION: Parenchymal damage in salivary glands induced by high-dose radioiodine therapy can be reduced significantly by amifostine. This may increase the quality of life of patients with differentiated thyroid cancer.

Quantitative salivary gland scintigraphy in the diagnosis of parenchymal damage after treatment with radioiodine.

This study was undertaken to quantify salivary gland parenchymal damage after radioiodine treatment with a standard protective regimen of ascorbic acid. Altogether, 106 patients underwent quantitative salivary gland scintigraphy with 99Tcm-pertechnetate prior to and 3 months after radioiodine therapy. Parenchymal function was quantified by calculating 99Tcm-pertechnetate uptake 13 min post-injection. Patients received 131I doses ranging from 400 MBq to 24 GBq (cumulative). Among the patients who received large doses of 131I, severe parenchymal destruction could be visually analysed as well as quantitatively evaluated. In contrast, after low-dose radioiodine treatment, mild parenchymal impairment was demonstrated by quantitative evaluation only. In conclusion, standardized quantitative salivary gland scintigraphy is essential for the reliable detection of mild parenchymal malfunction. Despite the standard protection regimen using ascorbic acid as a sialogogue, radioiodine therapy induces loss of salivary gland parenchymal function even with low doses of 131I.

Application of P-31 nuclear magnetic resonance spectroscopy to a new experimental kidney perfusion model using cadaveric porcine kidneys from slaughterhouse.

Larger NMR magnets with relatively high field strengths have become available recently, allowing the application of magnetic resonance spectroscopy (MRS) in larger mammalian organs. The aim of this study was to develop and test a new and simple kidney perfusion model from slaughterhouse swine using a new 4.7-tesla/40-cm diameter system, with the intention behind to provide a human-like mammalian experimental kidney perfusion model, and to avoid sensitive in vivo animal experiments on higher-developed mammalians, 35 pig kidneys obtained 10-15 min post mortem were studied to evaluate and define conditions for optimum metabolic preservation with the following perfusion protocols: (1) immediate plegia with cold Collins solution, 1-3 h cold storage, P-31 MRS; (2) immediate plegia, 1-3 h cold storage, blood reperfusion, P-31 MRS; (3) immediate blood reperfusion, plegia, 1-3 h cold storage, blood reperfusion, P-31 MRS; (4) immediate blood reperfusion, plegia, 24 h cold storage, blood reperfusion, P-31 MRS, P-31 MRS at 81 MHz with a double-tuned surface coil yielded the following results: [table: see text] Blood flow showed a weak correlation with beta-ATP/inorganic phosphate in protocols 3 and 4 of r = 0.64. Repeated reperfusion and ischemia experiments of this model allowed the on-line observation of the metabolic response of the energy phosphate pattern for several hours. In conclusion, slaughterhouse-harvested swine kidneys lend themselves to a simple, low-cost in vitro perfusion model, provided they are reperfused with arterial blood immediately after harvesting.(ABSTRACT TRUNCATED AT 250 WORDS)