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Biomedical subjects

J M de Klerk

Publications and source records attributed to J M de Klerk.

At least 19 recordsLinked to original sources

Efficacy of high therapeutic doses of iodine-131 in patients with differentiated thyroid cancer and detectable serum thyroglobulin.

Serum thyroglobulin (Tg) is usually the best marker of residual or metastatic disease after treatment of differentiated thyroid cancer. We evaluated the effect of so-called blind therapeutic doses of iodine-131 in patients with detectable Tg during suppressive levothyroxine treatment (Tg-on), and in patients with a negative diagnostic scintigram but detectable Tg during the hypothyroid phase (Tg-off). Twenty-two patients with differentiated thyroid carcinoma underwent total thyroidectomy and radioiodine ablation. During the follow-up, six patients with detectable Tg-on and 16 patients with detectable Tg-off were identified. All patients were treated with a blind therapeutic dose of 7,400 MBq iodine-131. Diagnostic scintigrams were compared with post-treatment scintigrams. Tg-off was measured in 16 cases, 1 year after the administration of the blind therapeutic dose, at the time of the follow-up diagnostic scintigram. Six patients were followed up by Tg-on only. Post-therapy scintigrams revealed previously undiagnosed local recurrence or distant metastases in 13/22 cases (59%); the remaining nine post-therapy scintigrams were negative. At the time of the blind therapeutic doses, Tg-off values ranged from 8 to 608 microg/l. After 1 year of follow-up, Tg-off decreased in 14/16 (88%) patients. In all patients who were followed by Tg-on only (n=6), a decrease in Tg values was measured. It is concluded that blind therapeutic doses resulted in a decrease in Tg levels in the majority of patients with suspected recurrence or metastases. The post-treatment scintigrams revealed pathological uptake in 59% of patients.

Adult↗

Quantitative baseline renography 48 hours after renal transplantation predicts long-term graft survival.

Technetium-99m mercaptoacetylglycine (99mTc-MAG3) renography is a successful non-invasive method for the evaluation of renal transplants. In this study we prospectively studied 256 patients after renal transplantation, using the MAG3 uptake capacity in the first 10 min (MUC10), which is an index of renal function representing kidney activity as a fraction of the injected dose. Renal scintigraphy was performed in all patients within 48 h of transplantation. Renograms were obtained over 20 min, after bolus injection of +/-100 MBq 99mTc-MAG3. MUC10 ranged between 0.0 and 94.9. The patients were divided into five groups: group 1, MUC10 <1; group 2, 1< or =MUC10 < 5; group 3, 5 < or = MUC10 <10; group 4, 10 < or = MUC10 < 30; group 5, MUC10 > or =30. In 235 patients, follow-up for 5 years was completed. Considering all the renal transplants, 30% of the grafts ceased functioning within the first 5 years. Six grafts showed a MUC10 of < 1, and none survived the first year. After 5 years, 43% of the grafts with a MUC10 of 1-5 still functioned, as compared with 63% of those with a MUC10 of 5-10, 72% of those with a MUC10 of 10-30 and 83% of those with a MUC10 of > or =30. Kaplan-Meier survival analysis showed significant differences between the five different patient groups based on MUC10 in terms of the percentage of kidneys that ceased to function within 5 years. The period of cold ischaemia and the donor age were known in 178 patients. In contrast to cold ischaemia time, the MUC10 and the donor age showed a significant effect (P<0.05) on graft survival. This study indicates that the MUC10 early after renal transplantation is useful as a prognostic factor in the evaluation of kidney transplants and that a MUC10 of <1 indicates a dismal prognosis for the renal transplant.

Adult↗

Interferon-alpha induced changes in CEA expression in patients with CEA-producing tumours.

Enhancement of antigen expression could result in improved tumour targeting using antibodies directed to the antigen. In this study we performed radioimmunoscintigraphy using 99mTc-CEA-Scan to analyse the effect of interferon-alpha (IFN-alpha) in enhancing the expression of carcinoembryonic antigen (CEA) in ten patients with CEA-producing tumours. Furthermore, we investigated the feasibility of a future therapeutic study with this antibody fragment labelled with rhenium-186. Although IFN-alpha gave rise to a significant increase in antibody uptake by the tumour, the absolute antibody uptake in the tumour appeared to be poor, with a mean of 0.475% of injected dose (ID) in the tumour before IFN-alpha, rising to 0.562% ID in the tumour after IFN-alpha. Pharmacokinetic analysis demonstrated no significant alterations after IFN-alpha. In conclusion, the administration of IFN-alpha is an attractive way to achieve enhanced tumour targeting, although the increase was of little clinical significance in this patient population and using this antibody fragment.

Adult↗

Fluorodeoxyglucose positron emission tomography, a new technique for increasing the detection rate of coincident thyroid cancer in head and neck oncology.

Clinically occult thyroid cancer is not uncommon and may occur in 1% to 10% of the population Since the first studies on the use of fluorodeoxyglucose positron emission tomography (FDG PET) in clinical oncology some reports have appeared on the detection of occult tumors using this imaging modality. According to these results, the number of patients with head and neck cancer and clinically occult coincident primary tumors at initial presentation may be expected to increase. In two of the four patients presented, the coincident tumor was detected with FDG PET. The possible role of this new imaging technique is discussed in correlation with treatment and clinical outcome.

Adult↗

Radioimmunodiagnosis and therapy.

Although promising results with radioimmunotherapy and radioimmunodiagnosis in haematological diseases, have been reported, they are less encouraging results in solid tumours. Experimental mathematical models suggest that optimization of antibody-based therapy and diagnosis is possible and that further research towards improvement is warranted. In this review, the major problems of radioimmunotherapy and diagnosis are discussed. Particular items adressed include tumour uptake of antibodies and antibody-fragments, the target/non-target ratio, immunogenicity and the selection of radionuclides.

Antibodies, Monoclonal↗

Fixed dosage of 131I for remnant ablation in patients with differentiated thyroid carcinoma without pre-ablative diagnostic 131I scintigraphy.

Differentiated thyroid cancer is treated by (near) total thyroidectomy followed by radioiodine (131I) ablation of the residual active tissue in the thyroid bed. Controversy remains concerning the use and the dose of pre-ablative diagnostic 131I scintigraphy. This study was designed to assess the efficacy of thyroid ablation by high-dose 131I without pre-ablative diagnostic 131I scintigraphy. Ninety-three patients were treated with (near) total thyroidectomy and with a high ablative dose of 131I (3700-7400 MBq). A preablative 131I diagnostic scintigram was not performed. To assess the efficacy of the treatment, all patients were studied with a diagnostic 131I scintigram and with thyroglobulin plasma assays 1 year later after withdrawal of L-thyroxine for 4-6 weeks. The main criterion for a successful ablation was the absence of thyroid bed activity. An additional criterion was a thyroglobulin value of <10 microg x l(-1). Successful ablation according to the main criterion was obtained in 88% of patients. Forty patients (43%) showed no neck uptake and had undetectable serum thyroglobulin. Twenty-two patients (25%) had serum thyroglobulin concentrations between 1 and 10 microg x l(-1). Twenty-six patients (27%) had thyroglobulin >10 microg x l(-1), 19 patients showing residual thyroid uptake or metastatic lesions. We conclude that high-dose radioiodine ablation without prior diagnostic scintigraphy results in a high rate of successful ablation, preventing repeat 131I treatment.

Adult↗

Iodine-131 uptake and turnover rate vary over short intervals in Graves' disease.

From a Dutch questionnaire, it was apparent that nearly all institutions used percentage of radioiodine uptake for calculation of the radioiodine dose in Graves' disease. Although there is a general belief that fluctuations in radioiodine uptake may occur, with few exceptions relatively long intervals were accepted between the uptake measurement and the actual therapy dose. With the aim of optimizing the pretherapeutic work-up, we evaluated the stability of iodine uptake over time in patients with Graves' disease who were referred for 131I therapy. 131I uptake was measured in 300 consecutive patients for the calculation of the required 131I therapy dose; data were complete for 291 patients (97%). After discontinuing thyroid medication for 3 days, standardized thyroid probe measurements were performed 5 and 24 h after ingestion of a capsule containing 0.37 MBq 131I-NaI. Measurements were performed at the time of scintigraphic diagnosis (test 1), as well as immediately before 131I therapy (test 2). The time interval between test 1 and test 2 ranged from 2 to 421 (median 40) days. A relative increase or decrease greater than 10% between tests 1 and 2 occurred in 180 of 291 cases (62%) at 5 h and in 158 of 291 patients (54%) at 24 h. These changes were not related to the interval between the tests or to initial uptake values, thyroid mass, gender or age. Rapid turnover of radioiodine (5 h/24 h uptake ratio > 1) was noted in 17% of the patients during test 1 and in 15% during test 2. Rapid turnover was persistent (present in both tests 1 and 2) in only 9%. We conclude that patients with Graves' disease show considerable changes in 131I uptake over relatively short periods of time, and the turnover rate of 131I in this condition is not constant.

Adult↗

Aspirin renography and captopril renography in the diagnosis of renal artery stenosis.

UNLABELLED: Preliminary data suggest that aspirin renography is more sensitive than captopril renography for indicating renal artery stenosis (RAS). Considering that aspirin, compared with captopril, reduces renal blood flow and, thus, tubular tracer delivery in poststenotic kidneys, aspirin renography is expected to be more useful, particularly if tubular tracers are used. METHODS: We prospectively compared aspirin renography (20 mg/kg orally) and captopril renography (25 mg orally) with 99mTc-mercaptoacetyltriglycine in 75 consecutive patients suspected of having RAS. RESULTS: RAS, diagnosed as stenosis of more than 50% on angiography, was found unilaterally in 34 patients and bilaterally in 17 patients. RAS was absent in 24 patients. The sensitivities for unilateral RAS or bilateral RAS (i.e., stenosis that was at least unilateral) were, respectively, 88% and 88% for captopril renography and 82% and 94% for aspirin renography (not significant). The overall specificity was 75% for captopril renography and 83% for aspirin renography (not significant). Tracer uptake ratios, time to peak activity, and percentage of 20-min tracer retention were also not significantly different for captopril and aspirin renography. Subgroup analysis of modest (50-75%) and severe (> or =75%) RAS, or of plasma creatinine greater than 120 micromol/L, also showed no difference between captopril and aspirin renography. CONCLUSION: We conclude that for identification of RAS, the usefulness of aspirin renography equals, but does not surpass, that of captopril renography.

Aged↗

Can bone marrow scintigraphy predict platelet toxicity after treatment with 186Re-HEDP?

The toxicity of 186Re-1,1-hydroxyethylidene diphosphonate (186Re-HEDP) therapy in patients with painful bone metastases is mainly limited to thrombocytopaenia. The aim of this study was to investigate the influence of bone marrow scintigraphy on the prediction of decreased platelet counts after 186Re-HEDP therapy. Twenty-nine prostatic cancer patients with multiple painful bone metastases were included in the study. From a pre-therapy nanocolloid bone marrow scintigram, the bone marrow index (BMI) was determined as an indicator of the extent of bone marrow involvement. The influence of the BMI on the prediction of percent decrease in platelet counts was investigated. The mean BMI was 59 +/- 20. Regression analysis showed that the BMI does not improve the relationship between percent reduction in platelet count and administered dose. In contrast, we previously showed that the bone scan index (BSI) does predict the percent reduction in platelet counts before treatment. We conclude that bone marrow scintigraphy does not provide any additional information on platelet toxicity after a therapeutic dose of 186Re-HEDP. Bone scintigraphy is preferred in the prediction of reduced platelet counts.

Aged↗

Integrated visualization of functional and anatomic brain data: a validation study.

UNLABELLED: Two-dimensional SPECT display and three methods for integrated visualization of SPECT and MRI patient data are evaluated in a multiobserver study to determine whether localization of functional data can be improved by adding anatomical information to the display. METHODS: SPECT and MRI data of 30 patients were gathered and presented using four types of display: one of SPECT in isolation, two integrated two-dimensional displays and one integrated three-dimensional display. Cold and hot spots in the peripheral cortex were preselected and indicated on black-and-white hard copies of the image data. Nuclear medicine physicians were asked to assign the corresponding spots in the image data on the computer screen to a lobe and a gyrus and give a confidence rating for both localizations. Interobserver agreement using kappa statistics and average confidence ratings were assessed to interpret the reported observations. RESULTS: Both the interobserver agreement and the confidence of the observers were greater for the integrated two-dimensional displays than for the two-dimensional SPECT display. An additional increase in agreement and confidence was seen with the integrated three-dimensional display. CONCLUSION: Integrated display of SPECT and MR brain images provides better localization of cerebral blood perfusion abnormalities in the peripheral cortex in relation to the anatomy of the brain than single-modality display and increases the confidence of the observer.

Cerebral Cortex↗

186Re-etidronate in breast cancer patients with metastatic bone pain.

UNLABELLED: The aim of this study was to evaluate the efficacy of 186Re-1,1-hydroxyethylidene diphosphonate (etidronate) in breast cancer patients with painful bone metastases. METHODS: Thirty patients with advanced breast cancer who had metastatic bone pain were treated with 186Re-etidronate using different dosages in a noncomparative, open-label study. Twenty-four patients were evaluated for efficacy (6 patients had incomplete datasets). Dosages varied from 1295 to 2960 MBq (35 to 80 mCi). Efficacy was evaluated according to the multidimensional pain model using a paper-and-pencil diary. The diary was kept twice daily for 8-10 wk (2 wk before through 6-8 wk after 186Re-etidronate treatment). Response was determined with a strict criteria, in which pain intensity (PI), medication index (MI) and daily activities (DA) were core determinants. Response was defined as: (a) Reduced PI > or = 5% while MI and DA were at least constant; or (b) Reduced PI <25% in combination with improvement of MI or DA > or = 25%, without worsening of either factor. Duration of response should always exceed a minimum of 2 wk. RESULTS: Fifty-eight percent (n = 14) of all patients reported a response. The maximum follow-up period was 8 wk. Duration of response ranged from 2 to 8 wk (mean 4 wk). Patients (14/24) not only experienced considerable pain reduction, but in 12 patients this was also accompanied by noteworthy reduction in MI (> or = 25%). No clear dose-response relationship was found. CONCLUSION: With strict pain assessment criteria, 186Re-etidronate showed a response of 58% in the palliative treatment of metastatic bone pain originating from breast cancer.

Bone Neoplasms↗

[Hot spots: metastases or osteoporosis?].

Radionuclide bone scintigraphy is a sensitive but not a specific technique for the diagnosis of bone metastases. Three patients, a man of 67 on steroid therapy because of chronic obstructive pulmonary disease and prostate cancer, a woman of 76 on steroid therapy because of temporal arteritis and a 50-year-old man with pain in the back, had bone scintigrams showing abnormal uptake (hot spots). There were delays of months before the diagnosis of osteoporosis instead of bone metastases was made. Abnormal uptake on a bone scintigram is often non-specific and requires further evaluation using supplementary diagnostic techniques.

Aged↗

The value of renal scintigraphy in the conservative management of a patient with tuberous sclerosis.

The diagnostic dilemma to differentiate angiomyolipomas from renal cell carcinoma has been resolved by computerized tomography and sonography. However, these imaging modalities are incapable of estimating the functional contribution of individual kidneys. Renal scintigraphy can be used for a quantitative impression of renal function and is, therefore, of additional value in monitoring conservatively treated tuberous sclerosis patients as shown by the case report.

Adult↗

Iodine-131 therapy in sporadic nontoxic goiter.

UNLABELLED: The effect of radioiodine in the treatment of nontoxic goiter is seldom evaluated quantitatively. The aim of this study was threefold: (a) to assess the effect of 131I on goiter volume, (b) to establish a relationship between CT volume reduction and the amount of radioactivity taken up by the thyroid and (b) to assess the precision of scintigraphic thyroid volume measurements. METHODS: In 27 patients with sporadic nontoxic goiter, the thyroid volume was estimated from a [99mTc]pertechnetate scintigram. Two different models (cylinder model and surface model) were applied. The 131I dosage varied between 507 and 3700 MBq. In all patients, noncontrast CT scanning of the neck was performed before therapy and 1 yr after therapy. RESULTS: The mean CT thyroid volume before therapy was 194 +/- 138 ml. A reduction was obtained in all patients and averaged 34% +/- 17%. The volume reduction measured by CT correlated well with the amount of 131I in the thyroid (r = 0.70). In thyroids larger than 200 ml, both scintigraphic volume estimation methods were imprecise. For smaller volumes, the surface model was superior. Hypothyroidism developed in 14% of the patients. No other side effects occurred. CONCLUSION: Iodine-131 therapy for volume reduction in nontoxic goiter is a safe and effective treatment. For scintigraphic estimation of thyroid gland volumes smaller than 200 ml, the surface model is preferred.

Adult↗

Acute liver necrosis induced by iodine-131-MIBG in the treatment of metastatic carcinoid tumors.

Iodine-131-metaiodobenzylguanidine (MIBG) is used in the treatment of carcinoid tumors. Temporary palliation with complete subjective symptomatic response has been reported in these patients. This treatment is usually well tolerated and side-effects are generally limited to nausea, mild hepatic toxicity with spontaneous recovery and temporary myelosuppression. Our case report shows that repeated treatment with [131I]MIBG in a patient with extensive carcinoid liver metastasis may cause severe hepatic toxicity leading to death. Factors such as concomitant use of 5-fluorouracil and the progressive nature of the disease may have contributed to this event.

3-Iodobenzylguanidine↗

Bone marrow absorbed dose of rhenium-186-HEDP and the relationship with decreased platelet counts.

UNLABELLED: Rhenium-186(Sn)-1,1-hydroxyethylidene diphosphonate (186Re-HEDP) has been used for palliation of metastatic bone pain. The purpose of this study was to find a relationship between the bone marrow absorbed dose and the toxicity, expressed as the percentage decrease in the peripheral blood platelet count. METHODS: The bone marrow absorbed dose was calculated according to the MIRD model using data obtained from ten treatments of patients suffering from metastatic prostate cancer; noninvasive and pharmacokinetic methods were used. The bone marrow doses were related to toxicity using the pharmacodynamic sigmoid Emax model. RESULTS: The mean bone marrow absorbed doses using the noninvasive and pharmacokinetic methods were in a close range to each other (1.07 mGy/MBq and 1.02 mGy/MBq, respectively). There was a good relationship between the toxicity and the bone marrow absorbed dose (r = 0.80). Furthermore, the EDrm50 (i.e., the bone marrow absorbed dose producing a 50% platelet decrease) to bone marrow for 186Re-HEDP was on the order of 2 Gy. CONCLUSION: Although the function of normal bone marrow is affected by metastases in patients with metastatic bone disease, the MIRD model can be used to relate toxicity to the bone marrow absorbed dose after a therapeutic dosage of 186Re-HEDP.

Aged↗