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Aim: To study the clinical yield of diagnostic whole body 131 I scintigraphy (DxWBS) in the follow-up of differentiated thyroid carcinoma (DTC) patients in relation to stimulated thyroglobulin (sTg) in the initial post-ablation setting, as well as in the setting of repeated monitoring in course of further DTC follow-up., Methods: Data of 1420 thyroidectomized and radioiodine remnant-ablated DTC patients following a well-defined therapy and standardized follow-up protocol were evaluated. DxWBS and sTg were evaluated separately and in combination for various follow-up time points. The factual administration of the recorded indication for further oncologic therapy (excluding radioiodine therapies given for minimal normal remnants) within the following 4 months after follow-up served as the standard of reference. Furthermore, DxWBS was compared to post therapy WBS and SPECT(/CT) if available. Subgroup analysis was carried out for DTC patients < 45 years old at diagnosis without distant metastasis. The diagnostic impact of cervical ultrasound was not assessed., Results: sTg can identify the patients at risk better than DxWBS. Furthermore, the most sensitive time point to assess response appears to be a time point beyond 3 months after RRA. When information received from both imaging and laboratory measurements are concordant, i.e. both construe absence of remaining disease, only a small fraction of patients (<2%) required treatment in the future. The strongest effect was observed 12 months after RRA. Only 0.9% of the negative DxWBS patients with concordant sTg below the functional sensitivity at this time point required treatment thereafter., Conclusion: A complete omission of DxWBS in the post-RRA surveillance of DTC is justified once DxWBS is negative and sTg is below the functional sensitivity (with no evidence of thyroglobulin antibodies), as patients showing this combination of test results (especially 12 months after RRA) show an at worst marginal risk of recurrence. In all other cases DxWBS may still be justified.

Background: Brain metastases arise in roughly 0.9% of all cases of differentiated thyroid cancer. The median survival of adult patients with thyroid carcinoma that has metastasized to the brain is less than one year. Radioactive iodine treatment is only rarely given because its efficacy is not documented. In children, the situation may be different., Method: In 2005, a 15-year-old girl underwent thyroidectomy, and an oxyphilic variant of papillary thyroid carcinoma was found in ectopic thyroid tissue. The patient underwent oral, high-dose radioactive iodine treatment. The post-therapeutic I-131 whole-body scan revealed multiple metastases in the skeleton, lungs, and the soft tissues, along with physiological uptake of the residual thyroid tissue. Magnetic resonance imaging of the head revealed two brain metastases., Results: When the initial treatment was completed, additional age-adapted high-dose radioactive iodine treatment was given, up to a total activity level of 35 GBq. There followed a complete remission of all metastases in the brain, bones, lungs, and soft tissues. Computed tomography of the chest revealed stable residuals. Over the ensuing 7.5 years of follow-up, the thyroglobulin values steadily declined to less than 2 ng/mL. The patient was asymptomatic at her last follow-up in May 2013. She did not develop any delayed reaction to high-dose radioactive iodine treatment (in particular, she did not develop leukemia or any other secondary malignancy). She remained fertile: after completion of the treatment, she had two healthy children., Conclusion: In this patient with multifocal thyroid carcinoma, a rare entity, radioactive iodine treatment was successful as the single treatment. This case illustrates the point that a given therapeutic modality might succeed in an individual case despite a total or near-total lack of efficacy for most patients in the same situation.

Unlabelled: Differentiated thyroid carcinomas (DTC) have an excellent prognosis, with 10-year overall survival rates over 90%. In addition, DTC patients benefit from their lifelong medical surveillance. The AIM of the study was to compare the patients' overall survival with that of a matched general population., Patients and Methods: We have analyzed 1497 consecutive patients with DTC, who underwent radioiodine therapy in Münster, Germany, according to international standards. We classified our patients according to the current 7th edition of the UICC (Union Internationale Contre le Cancer) classification and we compared the overall survival of the patients with the expected survival based on age and sex of the general population as provided by the Federal Statistical Office, Germany., Results: There were no significant differences in overall survival rates between DTC patients of the cohort in stages I to IVa compared to the expected survival based on age and sex of the general population. However, patients in stage IVc showed a significantly worse overall survival rate using the log-rank test (p < 0.0001)., Conclusion: Patients with DTC showed excellent overall survival rates in stages I, II, III and IVa. All patients, except for those in stage IVc (M1 ≥ 45 years), had overall survival rates similar to the general population.

Aim: Radioiodine remnant ablation (RRA) after (near-)total thyroidectomy (TE) is a key element in patients with differentiated thyroid cancer (DTC). The use of exogenous TSH stimulation (rhTSH) prior to RRA has shown promising results as compared to conventional thyroid hormone withdrawal (THW). As yet, the efficacy of RRA after brief THW and single rhTSH administration has not been assessed., Patients, Methods: The study sample comprised 147 patients with DTC referred to our center between May 2008 and September 2010. All patients received TE with subsequent RRA. None of these 147 patients had evidence of distant metastasis. 93 patients had endogenous TSH stimulation 4-5 weeks after surgery (group I) and twenty-six received two rhTSH injections (group II). 28 patients were treated with a single rhTSH injection after a brief THW (group III). RRA-Efficacy was assessed three months after therapy by diagnostic whole-body scan and measurement of the tumour marker thyroglobulin (Tg) under TSH stimulation., Results: Three categories of success were defined for remnant ablation. Based on the definition of successful remnant ablation no visible uptake and a Tg ≤ 2.0 ng/ml (category 1) was seen in 62/93 patients in group I, in 17/26 patients in group II (p = n.s.) and in 12/28 patients in group III (p < 0.05). Visible radioiodine uptake and a Tg ≤ 2.0 ng/ml (category 2) was seen in 16/28 patients of group III and thus significantly more frequent than in group I (28/93 patients) (p < 0.01). However, patients in group III (16/28 patients) and group II (8/26 patients) showed no significant difference in this category (p = n.s.). Visible radioiodine uptake and a Tg > 2.0 ng/ml (category 3) was found in 3/93 patients in group I and 1/26 patients in group II but in no patient in group III., Conclusion: The third strategy of remnant ablation using a single injection of rhTSH after a brief THW period resulted in a significant higher rate of patients with residual uptake in the thyroid bed and a Tg level below 2 ng/ml three months after remnant ablation in comparison to THW. However, the overall efficacy of the third protocol was not significantly different as compared to two rhTSH injections. Under the aspect of the supply shortage of rhTSH the combined endogenous and exogenous TSH stimulation may be an attractive alternative for remnant ablation in differentiated thyroid cancer.

According to the literature, the prevalence of papillary thyroid microcarcinoma (PTMC) is increasing. To date, PMTC account for up to 30% of all differentiated thyroid cancers. Patients with PTMC have an excellent prognosis with a normal life expectancy. Because of the differential definitions of the PTMC, the therapeutic approaches of the national Scien-tific Societies have not been standardized. The therapeutic algorithms have to be adjusted with regard to thyroid surgery, radioiodine ablation and thyrotropin-suppressive therapy as well as follow-up. Recently, the Therapy Committee of the European Society of Nuclear Medicine (EANM) has recommended a risk-adapted therapy and follow-up. Risk factors which require a more aggressive therapeutic approach are multifocality, thyroid capsule infiltration, evidence of locoregional or distant metastasis and unfavourable histology. It was the aim of this review to evaluate the current therapeutic concepts in patients with PTMC from a nuclear medicine perspective.

Version 3 of the procedure guideline for (131)I whole-body scintigraphy (WBS) is the counterpart to the procedure guideline for radioiodine therapy (version 3) and specify the interdisciplinary guideline for thyroid cancer of the Deutsche Krebsgesellschaft concerning the nuclear medicine part. (131)I WBS 3-6 months after (131)I ablation remains a standard procedure in an endemic area for thyroid nodules and the high frequency of subtotal surgical procedures. Follow-up without (131)I WBS is only justified if the following preconditions are fulfilled: low-risk group pT1-2, pN0 M0 with histopathologically confirmed pN0, (131)I uptake <2%, (131)I WBS during ablation without any suspicious lesion, stimulated thyroglobulin (Tg)-level 3-6 months after ablation <2 ng/mL, and absence of anti-thyroglobulin-antibodies with normal recovery-testing. If patients from the low-risk group show normal (131)I WBS 3-6 months after ablation and stimulated Tg is of <2 ng/mL, there will be no need for additional routine (131)I WBS. If patients from the high-risk group show normal (131)I WBS and stimulated Tg-level of <2 ng/mL 3-6 months after ablation, the follow-up care should include repeated stimulated Tg-measurements. If the Tg-level remains below 2 ng/mL, an additional (131)I WBS will be not necessary. The recommended intervals for stimulated Tg-testing are adapted to the prior intervals for (131)I WBS-testing in the high-risk group. Increased anti-thyroglobulin-antibodies or incomplete recovery-testing make an individual strategy of follow-up care necessary, which include (131)I WBS.

The procedure guideline for radioiodine therapy (RIT) of differentiated thyroid cancer (version 3) is the counterpart to the procedure guideline for (131)I whole-body scintigraphy (version 3) and specify the interdisciplinary guideline for thyroid cancer of the Deutsche Krebsgesellschaft concerning the nuclear medicine part. Recommendation for ablative (131)I therapy is given for all differentiated thyroid carcinoma (DTC) >1 cm. Regarding DTC < or =1 cm (131)I ablation may be helpful in an individual constellation. Preparation for (131)I ablation requires low iodine diet for two weeks and TSH-stimulation by withdrawal of thyroid hormone medication or by use of recombinant human TSH (rhTSH). The advantages of rhTSH (no symptoms of hypothyroidism, lower blood activity) and the advantages of endogenous TSH-stimulation (necessary for (131)I-therapy in patients with metastases, higher sensitivity of (131)I whole-body scan) are discussed. In most centers standard activities are used for (131)I ablation. If pretherapeutic dosimetry is planned, the diagnostic administration of (131)I should not exceed 1-10 MBq, alternative tracers are (123)I or (124)I. The recommendations for contraception and family planning are harmonized with the recommendation of ATA and ETA. Regarding the best possible protection of salivary glands the evidence is insufficient to recommend a specific setting. To minimize the risk of dental caries due to xerostomia patients should use preventive strategies for dental hygiene.

The procedure guideline for radioiodine ((131)I) therapy and (131)I whole-body scintigraphy of differentiated thyroid cancer in paediatric patients is the counterpart to the procedure guidelines (version 3) for adult patients and specify the interdisciplinary guideline for thyroid cancer of the Deutsche Krebsgesellschaft concerning the nuclear medicine part. Characteristics of thyroid cancer in children are the higher aggressiveness of papillary thyroid cancer, the higher frequency of extrathyroidal extension and of disseminated pulmonary metastases as well as the high risk of local recurrences. Radioiodine therapy is generally recommended in children, the (131)I activity depends on the children's body weight. Radioiodine ablation in children with small papillary cancer (< or =1 cm) should be considered. TSH stimulation is reached two weeks (children) or three weeks (adolescents) after withdrawal of thyroid hormones. Anti-emetic drugs are highly recommended. CT of the chest and examination of pulmonary function are clearly indicated if there is any suspicion on metastases. 3-6 months after (131)I ablation, the (131)I whole-body scintigraphy is highly recommended as lymph node metastases are frequently detected in paediatric patients. Follow-up care should be arranged in shorter intervals than in adults to test the compliance and to adapt dosage of thyroid hormones to the children's body weight. Reference values of fT3 are higher in children than in adults. Evidence is insufficient to describe in which constellation the TSH may be kept within the low normal level. Therefore, TSH suppression is generally recommended.

Version 4 of the guideline for radioiodine therapy for benign thyroid diseases includes an interdisciplinary consensus on decision making for antithyroid drugs, surgical treatment and radioiodine therapy. The quantitative description of a specific goiter volume for radioiodine therapy or operation was cancelled. For patients with nodular goiter with or without autonomy, manifold circumstances are in favor of surgery (suspicion on malignancy, large cystic nodules, mediastinal goiter, severe compression of the trachea) or in favor of radioiodine therapy (treatment of autonomy, age of patient, co-morbidity, history of prior subtotal thyroidectomy, profession like teacher, speaker or singer). For patients with Graves' disease, radioiodine therapy or surgery are recommended in the constellation of high risk of relapse (first-line therapy), persistence of hyperthyroidism or relapse of hyperthyroidism. After counseling, the patient gives informed consent to the preferred therapy. The period after radioiodine therapy of benign disorders until conception of at least four months was adapted to the European recommendation.

It is assumed that the regulation of cardiac endothelin (ET) receptor density is abnormal in heart diseases. From that perspective, an ET receptor radioligand is needed to assess ET receptor density in vivo. The nonpeptidyl ET(A) receptor antagonist PD 169390 was labelled with radioiodine to give a putative radioligand for SPECT. Labelling with [125I]iodide and [123I]iodide was accomplished with good to excellent radiochemical yields. The affinities of the nonradioactive reference and those of selected precursor compounds for ET(A) receptors were determined, using [125I]iodine labelled endothelin-1 with mouse ventricular membranes. All employed substances exhibited potent in vitro pharmacological characteristics with Ki values comparable to that of the lead compound PD 156707. Biodistribution studies and scintigraphic imaging experiments in mice, however, showed no significant uptake of the [123I] derivative in the heart.

Aim: For the examination of the impact on clinical practice of the guidelines for differentiated thyroid carcinoma (DTC), treatment data from the ongoing Multicenter Study Differentiated Thyroid Carcinoma (MSDS) were analyzed., Patients, Methods: Patients were randomized to adjuvant external beam radiotherapy (RTx) or no RTx in addition to standard therapy in TNM stages pT4 pN0/1/x M0/x (UICC, 5th ed. 1997). All patients were to receive the same treatment regimen consisting of thyroidectomy, ablative radioiodine therapy (RIT), and a diagnostic 131I whole-body scintigraphy (WBS) 3-4 months after RIT., Results: Of 339 eligible patients enrolled between January 2000 and March 2004, 273 could be analyzed. Guideline recommendations by the German Society for Nuclear Medicine from 1999 and 1992 were complied with within 28% and 82% with regard to the interval between surgery and RIT (4 vs. 4-6 weeks), in 33% and 84% with regard to 131I activity for RIT (1-3 vs. 1-4 GBq; +/- 10%), and in 16% and 60% with regard to 131I activity for WBS (100-300 vs. 100-400 MBq; +/- 10%)., Conclusions: The 1999 guideline revision appears to have had little impact on clinical practice. Further follow-up will reveal if guideline compliance had an effect on outcomes.

The version 3 of the guideline for radioiodine therapy for benign thyroid diseases presents first of all a revision of the version 2. The chapter indication for radioiodine therapy, surgical treatment or antithyroid drugs bases on an interdisciplinary consensus. The manifold criteria for decision making consider the entity of thyroid disease (autonomy, Graves' disease, goitre, goitre recurrence), the thyroid volume, suspicion of malignancy, cystic nodules, risk of surgery and co-morbidity, history of subtotal thyroidectomy, persistent or recurrent thyrotoxicosis caused by Graves' disease including known risk factors for relapse, compression of the trachea caused by goitre, requirement of direct therapeutic effect as well as the patient's preference. Because often some of these criteria are relevant, the guideline offers the necessary flexibility for individual decisions. Further topics are patients' preparation, counseling, dosage concepts, procedural details, results, side effects and follow-up care. The prophylactic use of glucocorticoids during radioiodine therapy in patients without preexisting ophthalmopathy as well as dosage and duration of glucocorticoid medication in patients with preexisting ophthalmopathy need to be clarified in further studies. The pragmatic recommendations for the combined use of radioiodine and glucocorticoids remained unchanged in the 3rd version.

The procedure guidelines for radioiodine therapy (RIT) of differentiated thyroid cancer (version 2) are the counter-part to the procedure guidelines for (131)I whole-body scintigraphy (version 2) and specify the interdisciplinary guidelines for thyroid cancer of the Deutsche Krebsgesellschaft and the Deutsche Gesellschaft für Chirurgie concerning the nuclear medicine part. Compared with version 1 facultative options for RIT can be chosen in special cases: ablative RIT for papillary microcarcinoma

Papillary thyroid microcarcinomas

Aim: Elevated iodine intake is a serious problem in the diagnostic and therapeutic application of (131)iodine in patients with differentiated thyroid cancer. Therefore, iodine avoidance is necessary 3 months in advance. Additionally, endogenous stimulation requires withdrawal of thyroid hormone substitution for 4 weeks. Exogenous stimulation using recombinant human TSH (rhTSH) enables the continuous substitution of levothyroxine, which contains 65.4% of its molecular weight in iodine. Thus, a substantial source of iodine intake is maintained during exogenous stimulation. Although this amount of stable iodine is comparable to the iodine intake in regions of normal iodine supply, it may reduce the accumulation of radioiodine in thyroid carcinoma tissue. The aim of this study was to assess the iodine excretion depending on different ways of stimulation., Methods: Iodine excretion was measured in 146 patients in the long term follow up after differentiated thyroid carcinoma. Patients were separated into 2 groups, those on hormone withdrawal (G I) and rhTSH-stimulated patients on hormone substitution (G II)., Results: Iodine excretion was significantly lower in hypothyroid patients (G I, median 50 micro g/l, range: 25-600 micro g/l) than in those under levothyroxine medication (G II, median 75 micro g/l, 25-600 micro g/l, p <0.027). TSH in G I (median 57.0 micro U/ml, range: 14.4-183 micro U/ml) was significantly lower (p <0.001) than in G II (117 micro U/ml, 32.2-281 micro U/ml)., Conclusion: Iodine excretion was higher in patients under rhTSH-stimulation than after hormone withdrawal. This may indicate an increased iodine pool in rhTSH-stimulated patients (deiodination of levothyroxine), thus limiting the sensitivity of radioiodine scanning to the level of endogenous stimulation despite significantly higher TSH levels during rhTSH-stimulation.

Purpose: Scintigraphy using I-123-iodo-alpha-methyl tyrosine (IMT) is useful in the preoperative characterization of gliomas, in detecting recurrent glioma and in the biological re-evaluation of residual or recurrent tumours. A systematic evaluation of non-parenchymal brain tumours has not yet been performed. The aim of the present study was to evaluate IMT SPECT in the management of intracerebral metastases and lymphomas., Patients and Methods: IMT uptake was analyzed in 31 patients with 28 metastases of extracerebral solid tumours and 7 cerebral lymphomas. Histology revealed high grade lymphomas, melanomas, and carcinomas of the following origin: lung, unknown primary, breast, colon, renal cell, ovary, vagina, frontal sinus. IMT uptake was quantified as ratio between maximal tumour accumulation and average uptake in the contralateral hemisphere., Results: All tumours except two renal cell and one small cell lung carcinoma metastases accumulated IMT (91%). The highest IMT uptake was found in a metastasis of lung carcinoma. IMT uptake was highly variable and was similar in primary and in recurrent tumours., Conclusion: Significant accumulation of IMT is seen in the majority of tumours, so that this technique might be helpful for the management of cerebral metastases and lymphomas.

3-[(123)I]Iodo-L-alpha-methyl tyrosine ([(123)I]IMT) scintigraphy of extracranial malignant tumors has been described, but little is known about the transport systems involved in [(123)I]IMT uptake into extracranial tumor cells. Here, the precise kinetics of [(123)I]IMT transport into human Ewing's sarcoma cells (VH-64) was determined. The apparent Michaelis constant was of high affinity value (K(m)=41.7+/-3.9 microM) and maximum transport velocitiy amounted to V(max)=20.7+/-0.6 nmol x mg protein(-1) x 10 min(-1). Inhibition experiments revealed the predominance of [(123)I]IMT uptake via sodium-independent system L.

In clinical and research studies, images obtained using carrier-added meta-[123I]iodobenzylguanidine (c.a. [123I]MIBG) have shown quite variable quality, with varying levels of uptake in lung, liver and mediastinum; this is a significant problem for quantification of the myocardial uptake by means of region ratios. First experimental and preliminary human data in respect of no-carrier-added (n.c.a.) [123I]MIBG are indicative of improved imaging quality. The aim of the present study was to evaluate the clinical value of myocardial scintigraphy with n.c.a. [123I]MIBG in patients with tachyarrhythmias. The study population comprised 24 patients with tachyarrhythmogenic diseases routinely studied by cardiac single-photon emission tomography (SPET) with [123I]MIBG. Twelve of the 24 patients were studied with c.a. [123I]MIBG (seven females and five males; mean age 42+/-13 years, range 20-60 years), whereas the other 12 were studied with n.c.a. [123I]MIBG (ten females, two males; mean age 41+/-11 years, range 18-60 years, P=NS). For quantification of the specific uptake in the different organs, count ratios were calculated on SPET images acquired 4 h p.i. Visual analysis of all [123I]MIBG scans showed improved image quality (improved contrast between heart and neighbouring organs) in n.c.a. studies as compared with c.a. studies. A significantly higher heart/left atrial blood ratio was found in the n.c.a. studies as compared with the c.a. studies (10.3+/-3.2 vs 5.3+/-1.3, P=0.0003); furthermore, significantly higher heart/lung and heart/liver ratios (2.5+/-0.6 vs 1.5+/-0.3, P=0.0002, and 0.8+/-0.2 vs 0.6+/-0.1, P=0.0006, respectively) were obtained in the c.a. studies, whereas lung/left atrial blood and liver/left atrial blood ratios showed no significant differences (4.2+/-1.3 vs 3.6+/-1.1, P=0.39, and 13.7+/-5.2 vs 9.6+/-2.2, P=0.21, respectively). In conclusion, the use of n.c.a. [123I]MIBG yields a significantly higher myocardial uptake associated with improvement in contrast between the heart and neighbouring organs and is therefore superior to the commercially available c.a. [123I]MIBG for use in clinical and research studies of the myocardial presynaptic sympathetic nervous system. Furthermore, our data indicate that for quantification the use of a left atrial blood reference region of interest, which is only available on SPET studies, is to be recommended.

Unlabelled: Patients with idiopathic ventricular tachycardia or fibrillation have no additional structural or functional myocardial abnormalities. However, the inducibility of typical tachyarrhythmias by physical or mental stress or by catecholamine infusion suggests the involvement of the adrenergic system in the pathogenesis of these potentially life-threatening diseases., Methods: 45 patients with idiopathic right ventricular outflow tract tachycardia (RVO-VT), 25 patients with idiopathic left ventricular tachycardia (ILVT), 15 patients with idiopathic ventricular fibrillation (IVF) and 10 age-matched control patients were investigated in this study. Diagnoses were made on the basis of detailed evaluation of the results of two-dimensional echocardiography, left and right ventricular angiography, coronary angiography and endomyocardial biopsy. Local presynaptic norepinephrine re-uptake was assessed using the norepinephrine analog 1231-metaiodobenzylguanidine (MIBG), SPECT and semiquantitative 33-segment bull's-eye analysis., Results: Locally reduced 123I-MIBG uptake was found in 27 of 45 RVO-VT patients (60%), 5 of 15 ILVT patients (33%) and 17 of 25 IVF patients (68%). Unlike ILVT patients, RVO-VT and IVF patients had significantly reduced segmental 123I-MIBG uptake of the posterior wall compared with control patients., Conclusion: Patients with idiopathic tachycardia and fibrillation show abnormal 1231-MIBG uptake, which indicates presynaptic sympathetic dysfunction. RVO-VT and IVF patients exhibit significantly reduced 123I-MIBG uptake in the posterior left ventricular wall, whereas ILVT patients do not.

Introduction: In patients with differentiated thyroid carcinoma, elevated serum levels of thyroglobulin (hTg) may occur in spite of otherwise negative diagnostic procedures and in particular in spite of a negative iodine-131 scan. Positron emission tomography with F-18-deoxyglucose (FDG-PET) is a potentially useful method for the detection of metastatic lesions or the recurrence of thyroid cancer. We aimed to investigate whether FDG-PET is capable of detecting metastatic lesions or recurrence in patients with differentiated thyroid carcinoma, elevated serum levels of thyroglobulin, and otherwise negative diagnostic procedures, including the iodine-131 scan., Methods: From a group of 500 patients with differentiated thyroid carcinoma, a subgroup of 32 patients had elevated serum hTg-levels, negative iodine- 131 scans, negative cervical and abdominal ultrasound, and negative X-ray of the chest. In 12 of these patients (hTg 77.8+/-94.3 ng/ml, range 1.5-277 ng/ml, median 20 ng/ml), FDG-PET was performed. All but one FDG-PET study was performed in a state of hypothyroidism (TSH 75.8+/-32.2 microIU/ml, range 31-116 microIU/ml, median 74.6 microIU/ml)., Results: In 6 of the 12 patients investigated, the FDG-PET was positive. In three of the patients, the diagnosis was confirmed by computed tomography or magnetic resonance imaging. In patients with a positive FDG-PET finding, the hTg level was 146.7+/-90.1 ng/ml (23-277 ng/ml, median 144.5 ng/ml). In contrast, in patients with a negative finding the hTg level was only 9.0+/-7.6 ng/ml (range 1.5-17 ng/ml, median 8.1 ng/ml), P=0.01., Conclusion: These preliminary results show that in patients with differentiated thyroid carcinoma, elevated hTg levels, and otherwise negative "conventional" diagnostic procedures, FDG-PET is helpful in detecting metastatic lesions.

Unlabelled: Iodine-123-alpha-methyl tyrosine (IMT) allows the investigation of amino acid transport rate in brain neoplasms. It was the aim of this study to evaluate the potential of IMT-SPECT to diagnose the recurrence of gliomas after primary therapy., Methods: Using a triple-headed SPECT camera, the cerebral uptake of IMT was determined in 27 patients 22 mo, on average, after surgical removal of a primary brain tumor. Eighteen patients had suffered from high-grade gliomas, and nine had suffered from low-grade tumors. Four patients were examined before and after surgical revision of a presumed tumor recurrence. A total of 31 studies were evaluated. The final diagnosis was based on prospective clinicopathological follow-up. Recurrence was diagnosed in 23 cases, with marked clinical deterioration occurring 3.1 mo, on average, after SPECT, and was confirmed by histopathology in 14 instances. Eight cases were free of recurrence, as evidenced by inconspicuous clinical follow-up, ranging from 6 mo to 17 mo after SPECT in seven cases, and by clinical course and histopathology in the remaining subject., Results: Patients with recurrence had significantly higher ratios of IMT uptake in the tumor area to that in a background region than did patients without recurrence (2.27 +/- 0.59 compared to 1.47 +/- 0.29; p < 0.002). The best cutoff level of the IMT uptake ratio in the differentiation between recurrence and benign posttherapeutic lesion was 1.8. Using this study-specific discrimination threshold, the sensitivity and specificity of IMT-SPECT for detecting glioma recurrence were 18 of 23 (78%) and 8 of 8 (100%), respectively. The area under the binormal receiver operating characteristic curve, fitted to the data, was 0.90 +/- 0.06., Conclusion: Iodine-123-alpha-methyl tyrosine-SPECT is a promising new tool in the follow-up of patients with gliomas after primary therapy.

Unlabelled: Amino acid transport rate in gliomas can be assessed using SPECT and the amino acid L-123I-alpha-methyl tyrosine (IMT). This study attempted to correlate the uptake of IMT by gliomas with the proliferative activity and cellular density of these neoplasms., Methods: The study used 27 patients with gliomas, including 18 patients with high-grade tumors and nine patients with low-grade neoplasms. Amino acid transport rate was determined using IMT and the triple-headed SPECT camera. Proliferative activity was immunohistochemically assessed as the relative number of cells expressing the Ki-67 nuclear antigen; cellular density was evaluated using light microscopy., Results: Relative IMT uptake correlated significantly with the proliferative fraction of tumor cells (r = 0.6, p < 0.001). There was no significant correlation between IMT uptake and cellular density (r = 0.25, p > 0.05)., Conclusion: The uptake of the SPECT radiopharmaceutical IMT is related to proliferative activity rather than to the cellular density of gliomas.

In our attempt to develop radioiodinated serotonin 5-HT2 receptor imaging agents for routine clinical application with single photon emission computed tomography (SPECT), the [123I]iodinated compound 8-[3-(4-fluorobenzoyl)-propyl]1-(4-[123I]iodobenzoyl)- 1,3,8-triazaspiro[4,5]decan-4-one [123I]IBSP was prepared via no-carrier-added Cu(I)-assisted radio-iododebromination in acetic acid, followed by purification by means of reversed-phase HPLC in 70-90% radiochemical yield and high specific activities at a total synthesis time of 50 min. Moreover, [123I]-IBSP is stable up to 48 h in aqueous solution at room temperature and revealed appropriate lipophilicity (logP = 2.8) for good diffusion through the blood-brain-barrier. Competitive binding studies on rat brain membranes using [3H]ketanserin, [3H]SCH23390, and [3H]spiperone as radioligands (for 5-HT2, D1 and D2 receptors, respectively) indicated that IBSP has high affinity and selectivity for the serotonin 5-HT2 receptor (Ki = 7.0 nM) over the dopamine D2 (Ki = 153 nM) and D1 receptors (Ki = 265 nM). These data suggest that [123I]-IBSP may be a promising compound for studying 5-HT2 receptors with SPECT.

Use of iodine-123-alpha-methyl tyrosine (123I-IMT) allows investigation of the amino acid transport rate in gliomas. It was the aim of this study to compare the value of measurement of glucose metabolism with that of measurement of 123I-IMT uptake for the non-invasive grading of brain tumours. The study population comprised 23 patients with histopathologically proven primary brain tumours; 14 had high-grade gliomas, and nine low-grade brain neoplasms. Glucose metabolism was studied using an ECAT EXACT 47 positron emission tomography (PET) camera and fluorine-18 fluorodeoxyglucose (18F-FDG); 123I-IMT uptake was measured with the triple-headed single-photon emission tomography (SPET) camera, MULTISPECT 3. 18F-FDG and 123I-IMT uptake was quantified as ratios between the uptake by the tumour and contralateral regions of reference. Glucose metabolism and amino acid uptake of the brain tumours correlated significantly (r=0.71, P <0.001). Assuming discrimination thresholds between high-grade and low-grade tumours of 0.8 for 18F-FDG uptake and 1.8 for 123I-IMT uptake, the accuracy values of 18F-FDG PET and 123I-IMT SPET for differentiating between high-grade and low-grade tumours were 21/23 (91%) and 19/23 (83%), respectively. The difference in diagnostic performance was not significant on receiver operating characteristic analysis (P >0.4). It is concluded that there is no major difference between the PET investigation of glucose metabolism and the less expensive SPET measurement of amino acid uptake in terms of their accuracy in evaluating the malignancy grade of primary brain tumours. This encourages the performance of further studies to analyse the potential impact of 123I-IMT SPET on the therapeutic management of patients with brain tumours.

Aim: The diagnostic value of 123I-mIBG-scintigraphy, bone scintigraphy and catecholamine metabolites in the follow up of neuroblastoma stage IV will be evaluated., Methods: Nineteen children suffering from neuroblastoma were analysed retrospectively by 123I-mIBG-scintigraphy, bone scintigraphy and measurement of homovanillic acid, vanillic acid, neuronspecific enclose, lactate dehydrogenase, and ferritine. Follow up was 7-132 (median 36) months., Results and Conclusion: The significance of the methods was dependent on the time of diagnostic use. In principal, 123I-mIBG-scintigraphy has the highest diagnostic impact. For initial staging and diagnosis of recurrence a combination of all three methods can be used. On the contrary, follow up during chemotherapy is best documented by 123I-mIBG-scintigraphy, whereas bone scintigraphy is of limited and measurement of catecholamine metabolites of less diagnostic value.

Unlabelled: The influence of systematic structure variations on the biodistribution of positional isomers of N-(N'-dialkylaminoethylene)-[123I]iodobenzamide (ABA) derivatives in melanoma-bearing animals was investigated., Methods: Radioiodination of six bromo benzamide precursors was achieved by Cu(1)-assisted nonisotopic halogen exchange. Organ distribution, scintigraphic and metabolic studies were performed in nude mice bearing a human melanotic MM (SK-MEL 25). A patient suffering from melanotic melanoma underwent scintigraphy with a [123I]iodobenzamide., Results: High radiochemical yields of 80%-95% and specific activities of > 5 TBq/ mumole were obtained. Animal studies revealed specific tumor uptake of all compounds with longest retention of the most lipophilic derivative p-[123I]ABA 2-2. At shorter times, however, o-[123I]ABA 2-2 exhibited the highest tumor uptake (8.9% ID/g, 1 hr p.i., 10.9% ID/g, 4 hr p.i.). Metabolization of o-[123I]ABA 2-2, mainly to o-[123I]iodohippuric acid (OIH), followed by fast renal excretion of the metabolites lead to tumor/nontumor ratios (T/NT) of > 400 for tumor/blood, and > 70 for tumor/liver at 48 h p.i. Unknown metastases could be localized in a patient using o-[123I]ABA 2-2., Conclusion: The effects of the structure variation of iodobenzamides on their lipophilicity, metabolism and thus pharmacokinetics lead to the suggestion of o-[123I]ABA 2-2 as a favorable melanoma imaging agent.

Using single-photon emission tomography (SPET), the radiopharmaceutical l-3-iodine-123-alpha-methyl tyrosine (IMT) has been applied to the imaging of amino acid transport into brain tumours. It was the aim of this study to investigate whether IMT SPET is capable of differentiating between high-grade gliomas, low-grade gliomas and non-neoplastic brain lesions. To this end, IMT uptake was determined in 53 patients using the triple-headed SPET camera MULTISPECT 3. Twenty-eight of these subjects suffered from high-grade gliomas (WHO grade III or IV), 12 from low-grade gliomas (WHO grade II), and 13 from non-neoplastic brain lesions, including lesions after effective therapy of a glioma (five cases), infarctions (four cases), inflammatory lesions (three cases) and traumatic haematoma (one case). IMT uptake was significantly higher in high-grade gliomas than in low-grade gliomas and non-neoplastic lesions. IMT uptake by low-grade gliomas was not significantly different from that by non-neoplastic lesions. Diagnostic sensitivity and specificity were 71% and 83% for differentiating high-grade from low-grade gliomas, 82% and 100% for distinguishing high-grade gliomas from non-neoplastic lesions, and 50% and 100% for discriminating low-grade gliomas from non-neoplastic lesions. Analogously to positron emission tomography with radioactively labelled amino acids and fluorine-18 deoxyglucose, IMT SPET may aid in differentiating high-grade gliomas from histologically benign brain tumours and non-neoplastic brain lesions; it is of only limited value in differentiating between non-neoplastic lesions and histologically benign brain tumours.

The aim of this study was to assess the influence of variations in the size of regions of interest (ROIs) on uptake values in brain tumours of L-3-iodine-123-alpha-methyl tyrosine (IMT). In addition, we attempted to establish the influence of size of ROIs on levels of significance assessing differences in mean IMT uptake between high-grade and low-grade tumours. Relative IMT uptake was determined in 19 patients with brain tumours using a MULTISPECT 3 triple-headed camera. Reconstructed image resolution was 14 mm at FWHM. Ten of the subjects suffered from high-grade gliomas (WHO grade III or IV) and nine from benign brain tumours, including eight patients with low-grade gliomas (WHO grade II). ROIs were defined by selecting those pixels within the tumour that exhibited uptake values above predefined threshold values. Using threshold values of 100, 95, 90, 85 and 80% of the mean, transaxial ROI size was approximately 0.1, 2.8, 4.3, 6.2 and 8.8 cm2, respectively. Over this range, mean, IMT uptake values decreased significantly from 2.4 to 1.9. High-grade tumours exhibited significantly higher IMT uptake than low-grade tumours at each of the threshold values. The corresponding levels of significance calculated using the Mann-Whitney U-test were between 0.01 and 0.02. Although IMT uptake values in brain tumours are significantly dependent on ROI size, levels of significance assessing differences in IMT uptake between high-grade and low-grade tumours are relatively insensitive to variations in this parameter.

Glomus caroticum tumours belong to the non chromaffine paragangliomas. As the incidence is very poor with 1% in the collective of a vascular-surgery department, the correct diagnosis is preoperatively only found in 10-20% of the cases. The early detection of primary- or recurrence-tumour is important for the surgical proceedings. With advanced tumour-stage, i.e. with involvement of the carotid artery in the tumour-process, the perioperative mortality increases. Furthermore nerve lesions following surgical tumour-resection as a complication are more frequent. This case-report point out the importance of the somatostatin-receptor-scintigraphy in the differentiation of glomus caroticum tumour-recurrence and postoperative scar. In our patient the suspicion of tumour-recurrence came up already 2 years ago, but could not be verified by MRT and angiography.

Imaging cerebral GABAA receptor density (GRD) with single-photon emission tomography (SPET) and iodine-123 iomazenil is highly accurate in lateralizing epileptogenic foci in patients with complex partial seizures of temporal origin. Limited knowledge exists on how iomazenil SPET compares with magnetic resonance imaging (MRI) in this regard. We present a patient with complex partial seizures in whom MRI had identified an arachnoid cyst anterior to the tip of the left temporal lobe. Contralaterally to this structural abnormality, interictal electroencephalography (EEG) performed after sleep deprivation disclosed an intermittent frontotemporal dysrhythmic focus with slow and sharp waves. On iomazenil SPET images GRD was significantly reduced in the right temporal lobe and thus contralaterally to the MRI abnormality, but ipsilaterally to the pathological EEG findings. These data suggest that iomazenil SPET may significantly contribute to the presurgical evaluation of epileptic patients even when MRI identifies potentially epileptogenic structural lesions.

In order to evaluate the behaviour of N-(2-diethylaminoethyl)-4-[123I]iodobenzamide in malignant melanotic disease, we synthesized the bromo compound in a simple one-step reaction. Labelling was performed by non-isotopic bromine-iodine-123 exchange in radiochemical yields up to 60%. By means of isocratic high-performance liquid chromatography, the iodinated product could be isolated with high apparent specific activity. First clinical studies in patients with malignant melanoma using N-(2-diethylaminoethyl)-4-[123I]iodobenzamide showed moderate uptake of the tracer in the tumour and the suspected metastases in all patients. Most of the lesions were detectable with technetium-99m-diethylene triamine penta-acetic acid (DTPA) scintigraphy too, but we were able to detect additional, previously unidentified metastases with benzamide scintigraphy. This changed the therapeutic procedure in two of the five cases investigated so far.

Temporal changes in the distribution of N-isopropyl-(123I)p-iodoamphetamine (IMP) within the brain are measured with serial tomographic imaging. In the cerebellum there is a decrease in activity of 42% from the early [15-45 min postinjection (p.i.)] to the late (210-240 min p.i.) scan, while in the cortex the decrease is 18%, and in the basal ganglia there is no decrease within this time. In brain tumors there was no IMP uptake in the early as well as in the late scans, regardless of tumor type, perfusion rate, or blood-brain barrier dysfunction. In 11 of 43 patients with a cerebral infarction a real increase of 123I activity (mean +21%) was seen in the late images. This "filling in" phenomena might be useful in selecting patients for bypass surgery. In these patients the diaschisis cerebelli, seen in the early scans, disappeared in the late images. The regional distribution of IMP changes with time; spatial ratios might be blurred by temporal changes. High-flow areas such as visio-auditory centers can be delineated clearly after stimulation in fast early scans; in these areas the pharmacokinetics of 123I are different from other cortex regions. To get the full information from the IMP brain uptake, both spatial and temporal variation must be measured.

In the follow-up of differentiated thyroid carcinoma it is discussed whether the tumor-marker thyroglobulin can replace the 131I scan, especially when the thyroglobulin serum level is normal. A positive 131I scan of metastases in the follow-up of patients with differentiated thyroid carcinoma combined with a low serum thyroglobulin level is extremely rare. The literature shows a frequency of about 4%. Recently we found 3 cases with a positive 131I scan demonstrating pulmonary and bone metastases whereas the serum thyroglobulin level was low.

Twenty patients were submitted to thyroidectomy and treated with iodine-131. Ten out of them received 100 mCi, the other ten 200 mCi. The activity of the total body and of the blood was determined by experimental proceeding. The doses absorbed by blood and bone marrow were calculated on the basis of the experimentally determined values. For the exposure of the blood, a medium value of 0.44 rd/mCi was found after 100 mCi and a medium value of 0.47 rd/mCi after 200 mCi. The corresponding values for the bone marrow are 0.24 and 0.3 rd/mCi, respectively. The total exposure is thus not so high as has been indicated hitherto in literature.

59 post-therapeutic examinations of the bone marrow have been performed in 35 patients out of a group of 296 patients treated from 1969 through 1976 by postoperative iodine-131 irradiations for carcinoma of the thyroid gland. Seven patients had normal findings, twelve patients showed panmyelopathy as principal finding, and fourteen patients presented modifications of the three marrow systems in different degrees and combinations. Acute myeloid leukemia was demonstrated in two patients by examination of the bone marrow, in another case the same disease was diagnosed by an analysis of the peripheral blood count. Taking into account the dosimetric considerations of the authors and the three cases of leukemia observed within the total group of patients, a risk factor for leukemia of 7.0 X 10(-5) X rd-1 is calculated which is slightly higher than the leukemia induction rate communicated in literature (22/2646 patients; 1-2/100,000/rd/year).

In a retrospective study, the hematologic parameters of 296 patients treated with iodine-131 (average: 536 mCi) for carcinoma of the thyroid gland were evaluated with respect to the different doses applied. The average observation period was 65 months. The most frequent hematologic modification was thrombocytopenia which was found in 35%, followed by erythrocytopenia in 24% of cases. The normal concentration of leucocytes was decreased in 11% and increased in 23% of cases, however, the medium value calculated for all patients showed a decrease of leucocytes by 7%. Pancytopenias were found in 4.4% of cases. The most severe decreases were presented after high doses of radio-iodine (greater than or equal to 1000 mCi). Pancytopenia may be considered as one of the causes of the death of three patients.