The success of 131I ablation in thyroid cancer patients is significantly reduced after a diagnostic activity of 40 MBq 131I.

OBJECTIVE: Dosimetry studies have shown that activities of 131I as small as 10-20 MBq may cause a stunning effect. A result of this stunning effect may be a lower success rate of the ablative 131I therapy for differentiated thyroid carcinoma (DTC). The aim of this study was to determine whether pre-therapeutic uptake measurement with 40 MBq 131I causes a lower success rate of ablation. DESIGN: retrospective chart review study. PATIENTS, METHODS: In two hospitals the ablation protocols differed in one respect only: in the one hospital no diagnostic 131I was applied before ablation (group 1, n = 48), whereas in the other hospital a 24-h uptake-measurement with 40 MBq 131I was performed (group 2, n = 51). Included were all DTC patients without distant metastases who had undergone 131I ablation between July 2002 and December 2005, and who had returned for 131I follow-up. Successful ablation was defined as absence of pathological 131I uptake on diagnostic whole-body scintigraphy and undetectable thyroglobulin-levels under TSH stimulation. RESULTS: Overall, ablation was successful in 31/48 patients (65%) in group 1 and in 17/51 patients (33%) in group 2 (p=0.002). Multivariate analysis showed that pre-therapeutic uptake measurement using 40 MBq 131I was an independent determinant for success of ablation (p = 0.002). CONCLUSIONS: After applying a diagnostic activity of 40 MBq 131I before ablation, the success rate of ablation is severely reduced. Consequently, the routine application of 131I for diagnostic scintigraphy or uptake measurement prior to 131I ablation is best avoided.

Comparison of a 1-day and a 2-day protocol for lymphatic mapping and sentinel lymph node biopsy in patients with nonpalpable breast cancer.

PURPOSE: To compare the identification rate of the sentinel node in a 1-day protocol versus a 2-day protocol in patients with a nonpalpable breast carcinoma. METHODS: In the 1-day protocol an average dose of 120 MBq (99m)Tc-nanocolloid was injected intratumorally on the day of surgery, and in the 2-day protocol an average dose of 370 MBq (99m)Tc-nanocolloid was injected intratumorally the day before surgery. Both a gamma ray detection probe and patent blue were used to locate the sentinel node. RESULTS: In 57 of 67 patients (85%) treated in the 1-day protocol and in 51 of 56 patients (91%) treated in the 2-day protocol the sentinel node was detected (p=0.311). Of the patients in the 1-day protocol and the 2-day protocol, respectively, 18 (27%) and 13 (23%) showed metastasis (p=0.975) CONCLUSION: There was no significant difference in the identification rate of the sentinel node between the 1-day protocol and the 2-day protocol in patients diagnosed with a nonpalpable breast carcinoma.

Value of diagnostic radioiodine scintigraphy and thyroglobulin measurements after rhTSH injection.

UNLABELLED: Measurements of thyroglobulin (Tg) levels 72 h after administration of recombinant human thyrotropin (rhTSH) are recommended by the manufacturer in the follow-up of patients with differentiated thyroid carcinoma (DTC). In our department, Tg measurements are performed both 24 h and 72 h after administration of rhTSH, together with 72 h post rhTSH 131I whole body scintigraphy (WBS). The OBJECTIVE of this study is to compare the diagnostic usefulness of Tg measurements 24 and 72 h after rhTSH administration, and 131I WBS. PATIENTS AND METHODS: 181 patients were included who had been referred to our Nuclear Medicine Department for follow-up after 131I ablation of DTC. Tg measurements 24 h (Tg24) and 72 h (Tg72) after rhTSH, and 131I WBS, were done in all patients. The lower detection limit of Tg was 0,2 microg/l. RESULTS: 47 patients (26%) had detectable Tg levels: in 4/47 cases (8%) only Tg24 was detectable (always <1 microg/l), and in 6/47 cases (11%), only Tg72 was detectable. In 10/47 patients with detectable Tg-levels, Tg24 and Tg72 tested equally. In 27/47 cases, Tg24 was lower, and in 10/47 higher, than Tg72. Two patients with one or two positive Tg-test results also had a positive 131I WBS. In 8 patients (14%) only the 131I WBS was positive; an anatomical substrate for such a Tg-negative positive WBS was confirmed in only 2 patients. CONCLUSION: Tg-measurement 72 hours after rhTSH injection reveals all clinically relevant detectable Tg-levels. Diagnostic 131I scintigraphy may be omitted, even in high-risk patients.

Effects of sub-chronic nitrate exposure on the thyroidal function in humans.

No experimental data exist on the thyroid toxicity of nitrate among humans. We aimed to show that no significant antithyroid effect could be observed after exposure to a three times the acceptable daily intake of nitrate in humans. In a randomized controlled non-inferiority trial, 10 volunteers received 15 mg/kg sodium nitrate during 28 days whereas 10 control participants received distilled water. We performed 5- and 24-h measurements of thyroidal (131)I uptake (RAIU) before and at the end of the exposure period. Thyroid hormone plasma concentrations of T3, rT3, T4, TSH were also measured prior to and after exposure. Differences in RAIU between the intervention and the control groups at 4 weeks were 3.4% (95% confidence interval -0.5 to 7.3, and 4.8% (95% confidence interval -1.4 to 11.0, respectively, for the 5- and 24-h RAIU measurement. Plasma concentrations of thyroid hormones stayed normal. In conclusion, no significant effects on thyroidal (131)I uptake and thyroid hormones plasma concentrations were observed after sub-chronic exposition to 15 mg/kg sodium nitrate among humans.

The intra-articular distribution of 90yttrium does not influence the clinical outcome of radiation synovectomy of the knee.

OBJECTIVES: To assess the impact of the intra-articular distribution of (90)yttrium-citrate ((90)Y) on the clinical effect of radiosynoviorthesis (RSO) of the knee and on (90)Y leakage from this joint. METHODS: Patients with arthritis of the knee received 185 MBq (90)Y combined with a glucocorticoid, followed by clinical bed rest. Intra-articular (90)Y distribution, measured with a dual-head gamma camera immediately or after 24 hours, was scored as mainly diffuse or mainly focal. Leakage to regional lymph nodes, the liver and spleen was assessed with a dual-head gamma camera after 24 hours. Clinical effect was scored after 6 months by a composite change index (CCI), range 0-12; responders were defined as having a CCI > or =6. RESULTS: Seventy-eight knees of 69 patients, mostly suffering from undifferentiated arthritis (42%) or RA (28%), were treated. (90)Y distribution was mainly diffuse in 54% and mainly focal in 46% with clinical response rates of 40% versus 56%, respectively, p = 0.3. CCI was not correlated with distribution. (90)Y leakage was found only to the liver and the spleen (mean leakage 0.4% and 1.1%, respectively). Leakage was significantly less in case of diffuse intra-articular (90)Y distribution, whereas leakage to the liver was correlated with distribution (r = 0.68, p<0.001). (90)Y leakage was not correlated with CCI. CONCLUSIONS: Intra-articular (90)Y distribution does not influence the clinical effect of RSO of the knee. Although (90)Y leakage from the joint is less if (90)Y distributes diffusely in the joint cavity, leakage does not seem to hamper the clinical effect.

Lateralisation and depth of the internal mammary chain determined by scintigraphy and by ultrasonography: a comparative study in 124 primary breast cancer patients.

In 124 primary breast cancer patients the maximum values of the lateralisation of the internal mammary chain (IMC) and their corresponding depths could be determined by scintigraphy and ultrasonography in 77% and 85% of the cases, respectively. With respect to the lateralisation it appeared that these values were uncorrelated between the two methods. With respect to depth correlation was found (correlation coefficient 0.34; P=0.001). We conclude that substantial differences are noted. Irradiation of the IMC based on computed tomography treatment planning might be a better alternative.

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.

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.

Bilateral temporal lobe necrosis after radiotherapy: confounding SPECT results.

A patient with seizures and a contrast-enhancing temporal lesion after radiation therapy for a chondrosarcoma of the nasal septum is described. To differentiate between radiation necrosis and recurrent tumor, thallium-201 (201Tl) SPECT was used. 201Tl SPECT revealed high local accumulation suggesting tumor growth; however, pathologic examination demonstrated focal necrosis with reactive changes but without tumor. The 201Tl SPECT findings in this patient demonstrate a possible diagnostic pitfall in differentiating recurrent tumor from radiation necrosis.

Reverse discordant scintigraphy in diffuse goiter.

Both Tc-99m pertechnetate and radioactive iodine (I-123 NaI or I-131 NaI) are useful in thyroid scintigraphy. These radiopharmaceuticals yield similar functional information in most patients. Occasionally, however, discordant results have been reported in the literature (warm or hot on the pertechnetate image and cold on the radioiodide image). Most of these reports have concerned the solitary thyroid nodule. A case is presented here with diffusely decreased Tc-99m pertechnetate uptake and normal I-131 NaI uptake in a patient with a diffuse goiter and subclinical hyperthyroidism, so-called reverse discordant behavior.

Pulmonary embolism after thrombolysis of hemodialysis grafts.

The aim of this study was to determine the incidence of pulmonary embolization occurring after mechanical or pharmacomechanical percutaneous intravascular thrombolysis in 23 patients with occluded hemodialysis grafts. In all patients, pulmonary perfusion scintigraphy was performed before and immediately after thrombolysis. In eight (35%) of the patients, there was evidence of pulmonary embolism resulting from the interventional procedure; however, in only one was there clinical symptoms. It is concluded that there is substantial risk of pulmonary embolism in patients undergoing percutaneous intravascular thrombolysis for an occluded hemodialysis graft.

Persistent synovitis treated with radiation synovectomy using yttrium-90: a retrospective evaluation of 83 procedures for 45 patients.

The objectives were to investigate the efficacy and safety of yttrium-90 colloid (Y-90) synovectomy in joints with persistent synovitis and to examine the effect of a second synovectomy using a double dose after an initial inadequate response. Of the 45 patients at the University Hospital Utrecht who underwent Y-90 synovectomy between July 1987 and October 1995, the effectiveness and side-effects of all yttrium procedures (n = 83) were assessed retrospectively. Glucocorticoids were administered together with the yttrium, except in 1987. Radiation synovectomy had an overall success rate of 75% (complete or almost complete remission of synovitis) initially, i.e. within 1 month of the procedure, partly due to co-administration of glucocorticoids. However, in October 1995, only 17 joints (22%) were still in remission with a mean (S.D.) duration of remission of 20.8 months (22.0), range 1-95 months (median 16 months). In 60 joints (78%), synovitis was present at that time because of an unsatisfactory initial response to the Y-90 injection (19 joints) or recurrent synovitis during follow-up (41 joints); the mean (S.D.) duration of remission of these 60 joints was 3.3 months (5.9), range 0-22 months. A second injection of a double dose of Y-90 after an initial inadequate response (n = 8) did not contribute significantly to a better result. Short-term side-effects occurred in two cases after two Y-90 injections (2%) without glucocorticoid co-administration: a post-injection flare-up of synovitis and a local skin burn lesion. Persistent synovitis can be treated by Y-90 synovectomy with an overall success rate of 75% within 1 month. However, prolonged remission of synovitis is only achieved in 29% of joints with a good initial response. It does not appear worthwhile to perform a second synovectomy with a double dose if the initial response was inadequate. Y-90 synovectomy leads to only minor short-term side-effects (2%).

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.

Is 11C-flumazenil PET superior to 18FDG PET and 123I-iomazenil SPECT in presurgical evaluation of temporal lobe epilepsy?

OBJECTIVE: To determine the contribution of 18FDG PET, 11C-flumazenil PET, and 123I-iomazenil SPECT to the presurgical evaluation of patients with medically intractable complex partial seizures. METHODS: Presurgical evaluation was performed in 23 patients, who were considered candidates for temporal lobe resective surgery (14 females and nine males with a median age of 34 (range 13 to 50) years). The presurgical diagnosis was based on seizure semiology as demonstrated with ictal video recording, ictal and interictal scalp EEG recordings, and MRI. RESULTS: Eighteen patients had convergent findings in clinical semiology, interictal and ictal EEG with scalp and sphenoidal electrodes, and MRI that warranted surgery without depth EEG (DEEG). In five patients with insufficient precision of localisation, DEEG with intracerebral and subdural electrodes was performed. MRI showed abnormalities in 22 out of 23 patients. Of these 22, 18 had mesial temporal sclerosis. This was limited to the mesial temporal lobe in four and more widespread in the temporal lobe in 14 patients. In one patient only enlargement of the temporal horn was found and in three others only white matter lesions were detected. 18FDG PET showed a large area of glucose hypometabolism in the epileptogenic temporal lobe, with an extension outside the temporal lobe in 10 of 23 patients. Only in one of these patients DEEG showed extratemporal abnormalities that were concordant with a significant extratemporal extension of hypometabolism in 18FDG PET. 18FDG PET was compared with the results of scalp EEG: in none of the patients was an anterior temporal ictal onset in scalp EEG related to a maximum hypometabolism in the mesial temporal area. By contrast, the region of abnormality indicated by 11C-flumazenil PET was much more restricted, also when compared with DEEG findings. Extension of abnormality outside the lobe of surgery was seen in only two patients with 11C-flumazenil and was less pronounced compared with the intratemporal abnormality. Both 18FDG PET and 11C-flumazenil PET reliably indicated the epileptogenic temporal lobe. Thus these techniques provide valuable support for the presurgical diagnosis, especially in patients with non-lesional MRI or non-lateralising or localising scalp EEG recordings. In those patients in whom phase 1 presurgical evaluation on the basis of classic methods does not allow a localisation of the epileptogenic area, PET studies may provide valuable information for the strategy of the implantation of intracranial electrodes for DEEG. Previous studies have suggested that 11C-flumazenil binding has a closer spatial relationship with the zone of ictal onset than the area of glucose hypometabolism, but this study suggests rather that the decrease in the 11C-flumazenil binding simply reflects a loss of neurons expressing the benzodiazepine-GABA receptor. 11C-flumazenil PET did not prove to be superior to 18FDG PET. CONCLUSION: In 21 patients sufficient material was obtained at surgery for a pathological examination. In 17 mesial temporal sclerosis, in one an oligodendroglioma grade B, in another a vascular malformation and in two patients no abnormalities were found. Although all 21 patients with pathological abnormality showed hypometabolic zones with 18FDG PET and a decreased uptake in 11C-flumazenil binding, there was no strong correlation between pathological diagnosis and functional abnormal areas in PET. Grading of medial temporal sclerosis according to the Wyler criteria showed no correlation with the degree of hypometabolism in either 18FDG or 11C-flumazenil PET. The interictal 123I-iomazenil SPECT technique was highly inaccurate in localising the lobe of surgery.

Volume regulation in children with early relapse of minimal-change nephrosis with or without hypovolaemic symptoms.

The cause of sodium retention in nephrotic syndrome is unclear. Hypovolaemia has traditionally been labelled as the cause but there is evidence in adults of a renal disturbance as the main cause. We aimed to find out whether children with early nephrosis can be classified as hypovolaemic by objective measures. We measured blood volume, kidney function, and hormone concentrations in children with early relapse of minimal-change nephrosis. Three presentations could be defined. The first was patients with incipient proteinuria and normal plasma protein, characterised by sodium retention, increased renal plasma flow, and slightly increased aldosterone, but normal noradrenaline. The second was patients with severe proteinuria, hypoproteinaemia, and hypovolaemic symptoms, who had oedema, sodium retention, and high concentrations of plasma renin, aldosterone, and noradrenaline, low atrial natriuretic peptide, and low glomerular filtration rate. The third was patients with equally severe proteinuria and hypoproteinaemia, but without hypovolaemic symptoms; they had oedema, but no active sodium retention, and normal plasma hormones and glomerular filtration. Neither blood pressure nor blood volume discriminated patients with or without hypovolaemic symptoms. These findings show that children with early full-blown nephrosis can present both with and without hypovolaemic symptoms and laboratory signs, despite equally severe hypoproteinaemia, and also that sodium retention precedes the reduction in serum protein.

Gastric motility and emptying studies with radionuclides in research and clinical settings.

Scintigraphy remains the most reliable method to measure gastric emptying. Standardized dual-isotope radionuclide gastric emptying techniques and appropriate meals, which stimulate small bowel receptors and utilize correction factors for technical errors, are widely available for research purposes. It is now necessary to apply the same standardized techniques in clinical settings to make the test diagnostically worthwhile. It is possible to quantify gastric motor function scintigraphically and to apply this methodology to study the pathophysiology of gastric emptying in various motor disorders. Ambulatory gastric emptying methods with intraluminal gamma counting probes are currently under development.

Standardized radioiodine therapy in Graves' disease: the persistent effect of thyroid weight and radioiodine uptake on outcome.

OBJECTIVE: To assess the incidence of hypothyroidism, euthyroidism, and recurrent hyperthyroidism following a standard dose of Na131I (3.7 MBq or 100 microCi) per g thyroid tissue, adjusted for radioiodine tracer uptake. DESIGN: A single-centre prospective follow-up study from January 1990 to December 1992. SETTING: Academic Hospital in Utrecht, the Netherlands. SUBJECTS: Newly diagnosed patients with Graves' disease (n = 148). INTERVENTIONS: Radioiodine treatment at a standard dose of 3.7 MBq or 100 microCi per g thyroid tissue. MAIN OUTCOME MEASURES: Confidence interval testing of resulting thyroid status, defined by biochemical criteria. RESULTS: The overall cure rate was 70% (103 of 148 subjects), confidence interval (CI) 62-77%. A 90% incidence of hypothyroidism was found in patients with a small thyroid (less than 20 g). Recurrent hyperthyroidism was found significantly more often in subjects with a thyroid weight exceeding 60 g compared to those who had a thyroid of 9-59 g. More recurrences were found in subjects in the highest tertile of a 24-h radioiodine uptake test (> 80% uptake) compared to those in the lowest tertile (< 60% uptake). CONCLUSIONS: No uniform treatment results expressed per thyroid weight category were obtained, in spite of standardizing the treatment Na131I dose (3.7 MBq per g thyroid). Graves' patients with a thyroid smaller than 20 g and those with less than 60% 24-h radioiodine uptake have a 50-90% chance of hypothyroidism at the 12-month follow-up.

Spatial integration of multimodal brain images in cerebral infarction.

Different structural as well as functional imaging techniques are becoming increasingly important in the investigation of patients suffering from an ischemic stroke. Available imaging procedures usually provide complementary data, but the images can not easily be compared due to differences in patient positioning, angulation, and slice thickness. We studied the value of spatial integration of images from different modalities in a patient with an ischemic stroke and used skin markers to integrate the obtained information. Computed tomography (CT), magnetic resonance imaging (MRI), 99mTcHMPAO-single photon emission computed tomography (SPECT) and magnetic resonance spectroscopic imaging (MRSI) were performed in a patient, presenting with a right sided hemiparesis caused by an ischemic stroke. Combination of MRI with CT demonstrated that the infarction visible on CT and MRI corresponded in size and volume. Furthermore, structural and functional images could readily be integrated, thus allowing us to obtain accurate information in this stroke patient. Different imaging modalities provide complementary information in the acute phase of cerebral infarction and multimodality matching can be of great value for improvement of our understanding of the pathophysiology and course of ischemic stroke.

Identification of the side of epileptic focus with 123I-Iomazenil SPECT. A comparison with 18FDG-PET and ictal EEG findings in patients with medically intractable complex partial seizures.

123I-Iomazenil SPECT was performed in 17 patients who were considered candidates for surgery of epilepsy because of medically intractable complex partial seizures. In addition to this examination their presurgical evaluation consisted of long term ictal EEG-CCTV monitoring, CT, MRI and 18FDG PET. In eight patients intracranial ictal EEG recordings were performed. SPECT was assessed visually while PET data were analyzed quantitatively. Both SPECT and PET were compared to ictal EEG data and showed asymmetries in over 80% of patients in agreement with EEG findings. These three methods were in agreement in 65% of patients. SPECT showed abnormality contralateral to the EEG focus in one patient (6%) while PET always demonstrated ipsilateral dysfunction. It is concluded that 123I-Iomazenil SPECT may be considered a more economical and more widely available alternative to 18FDG PET in the presurgical evaluation of patients with medically intractable complex partial seizures. In this respect 123I-Iomazenil specifically reflects functional changes in the membranes of neurons while 18FDG is related to glucose metabolism not only of neurons but also of glial cells.