Somatostatin receptor imaging in intracranial tumours

The somatostatin analogue [¹¹¹In-DTPA-d-Phe¹]-octreotide (¹¹¹In-octreotide) allows scintigraphic visualization of somatostatin receptor-expressing tissue. While it is well known that a large variety of tissues express somatostatin receptors and ¹¹¹In-octreotide scintigraphy has a clearly defined role in various neuroendocrine diseases, the clinical value of ¹¹¹In-octreotide scintigraphy in brain tumours is still under clinical investigation. In 124 patients with 141 brain lesions (63 meningiomas, 24 pituitary adenomas, 10 gliomas WHO class I and II, 12 gliomas WHO class III and IV, 11 neurinomas and 2 neurofibromas, 7 metastases and 12 other varieties: three non-Hodgkin B-cell lymphomas, two epidermoids, one abscess, one angioleiomyoma, one chordoma, one haemangiopericytoma, one osteosarcoma, one plasmacytoma and one pseudocyst), ¹¹¹In-octreotide scintigraphy was performed 4–6 and 24 h after i.v. injection of 110–220 MBq ¹¹¹In-octreotide. Planar images of the head in four views with a 128×128 matrix and single-photon emission tomographic images (64×64 matrix) were acquired, and lesions were graded according to qualitative tracer uptake. Fifty-nine of the 63 meningiomas showed moderate to intense tracer uptake. Nine of 24 pituitary adenomas were visible; the remaining 15 did not show any tracer uptake. None of the class I and II gliomas with an intact blood-brain barrier were detected whereas 11/12 class III and IV gliomas showed ¹¹¹In-octreotide uptake. None of the neurinomas or neurofibromas were positive. Five of seven metastases were classified as positive, as were the osteosarcoma, two of three non-Hodgkin B-cell lymphomas, one abscess, one angioleiomyoma, one chordoma and one haemangiopericytoma. The other varieties (one non-Hodgkin B-cell lymphoma, two epidermoids, one plasmacytoma and one pseudocyst) did not show ¹¹¹In-octreotide uptake. The results demonstrate that a large variety of intracranial lesions express somatostatin receptors and therefore can be visualized by [¹¹¹In-DTPA-d-Phe¹]-octreotide scintigraphy. This technique can be valuable in the differentiation between meningiomas and pituitary adenomas, based on qualitative tracer uptake. [¹¹¹In-DTPA-d-Phe¹]-octreotide scintigraphy allows differentiation between meningiomas and neurinomas or neurofibromas and therefore provides complementary information to computed tomography or magnetic resonance imaging. Furthermore, this technique allows differentiation between scar tissue and recurrent meningiomas postoperatively and can help in non-invasive tumour differentiation of multiple intracranial lesions, which can be of value in defining the most adequate therapeutic strategy. Received 1 December 1997 and in revised form 17 March 1998     

Usefulness of technetium-99m hydroxymethylene diphosphonate scans in localizing bone metastases of differentiated thyroid carcinoma

Iodine-131 is uniquely able to demonstrate iodine uptake of differentiated thyroid carcinoma (DTC), but precise localization may be difficult, especially in the thorax, due to the quality of image resolution with 1311 and the lack of anatomical landmarks. When bone metastases do not show radioiodine uptake, bone scintigraphy can be used to detect them. We studied two groups of patients. In group 1, 15 patients with known bone metastases of DTC were treated with 3.7 GBq ¹³¹I. After 4 or 5 days, technetium-99m hydroxymethylene diphosphonate (HMDP; 740 MBq) was injected and a whole-body scan with simultaneous acquisition of ¹³¹I and ^99mTc-HMDP images was carried out using a large field of view gamma camera fitted with a high-energy collimator. Technetium uptake was abnormal in 47 of 63 localizations, being increased in 29 foci, decreased in 7 and heterogeneous in 11. The superimposition of ¹³¹I and ^99mTc-HMDP scans permitted an accurate localization in 80% of spine metastases and in 46% of osseous thoracic localizations, even in the presence of lung metastases. In group 2, 9 patients, who had bone pain, neurological signs or elevated serum thyroglobulin, had DTC bone metastases without iodine uptake. They received a diagnostic dose of ^99mTc-HMDP 3h prior to scintigraphy with a large field of view gamma camera fitted with a low-energy collimator. Technetium uptake was abnormal in 37 of 38 localizations, being increased in 34 foci and decreased in 3. One false-negative was found in a skull metastasis. In both groups of patients, ^99mTc-HMDP scans were useful. The procedure allows accurate localization of bone metastases and can be used as a guide for subsequent radiological investigations.     

Low levels of serum thyroglobulin after withdrawal of thyroid suppression therapy in the follow up of differentiated thyroid carcinoma

We evaluated the reliability of very low serum thyroglobulin (Tg) levels (< 3 ng/ml) obtained after withdrawal of thyroid suppression therapy in 224 patients without anti-Tg antibodies, who had undergone total thyroidectomy (125 patients) or thyroidectomy followed by 1 or more courses of¹³¹I therapy (99 patients), by performing whole body scans after a therapeutic course of¹³¹I given at the same time of Tg measurement. In 79 patients (35%) a positive scan, associated with a very low level of Tg, was noted. The 1311 uptake was limited to the thyroid bed in 60 patients, but metastases were demonstrated in 19 patients (8.5%). These results are mainly explained by the much improved performance of scintigraphy after administration of therapeutic doses of¹³¹I. In the majority of patients, especially those whose¹³¹I uptake was limited to the thyroid bed, further scans were negative. Therefore, in these cases, negative Tg values can generally be considered an early indication of satisfactory evolution. However, in 8.5% of all cases, very low Tg levels were associated with metastases. Thus the follow up of thyroid cancer should not rely only upon Tg determination, even after suppression therapy withdrawal.Presented in part as an oral communication at the European Nuclear Medicine Congress, Budapest, Hungary, 1987     

Iodine-131 treatment and high-resolution CT: results in patients with lung metastases from differentiated thyroid carcinoma

Between 1984 and 2002, pulmonary metastases were detected in 42 (4%) out of 1,023 patients with differentiated thyroid carcinoma (DTC) in our department. The age at diagnosis ranged from 6 to 77 years. Lung metastases were diagnosed by both increased thyroglobulin (Tg) levels and positive uptake of iodine-131 on scans, and/or positive radiological findings. The primary tumours were histologically classified as papillary (30 patients), follicular (nine patients) and poorly differentiated (two tall cell, one insular carcinoma). The duration of follow-up ranged from 24 to 228 months. The end-results of the ¹³¹I therapy were evaluated. The treatment of choice was ¹³¹I therapy of metastases after total thyroidectomy plus lymph node dissection (if lymph node metastases were present). Applied single and total ¹³¹I activities were 1.8–10.4 GBq and 5.5–43.7 GBq, respectively. Lung metastases were present at the time of diagnosis in 30 patients and developed during the follow-up period in the remaining 12. Twelve patients with extensive metastases died of thyroid carcinoma and another died due to secondary malignancy (malignant mesothelioma). Ten patients with lung metastases remain completely free of disease and are probably cured, while another seven were stable at the time of study. Three- and five-year survival rates were 86% (36/42) and 76% (32/42), respectively. To define the diagnostic value of high-resolution computed tomography (HRCT) and identify the distinctive features of lung metastases from DTC, 22 patients were further examined with HRCT within 2 weeks of the initial diagnosis of lung metastases and the results were compared with chest X-ray findings. HRCT detected metastases in 10 out of 14 patients with a normal chest X-ray and confirmed metastases in all patients with positive (n=5) and suspicious (n=3) chest X-ray. HRCT did not show any abnormalities in four patients with positive lung uptake on ¹³¹I whole-body images. Stage of disease, existence of distance metastases other than to the lung, and HRCT characteristics were significant prognostic variables. Lung metastases from DTC can be cured with ¹³¹I therapy in a considerable number of patients, especially when they are not associated with other distant metastases; they should therefore be treated at an early stage. HRCT clearly improved diagnostic ability in the evaluation of lung metastases compared with chest X-ray and should be the primary method when radiological correlation is needed. The main, and new, finding of the study is that HRCT not only improves diagnostic ability but is also of prognostic value.     

Fluorine-18 fluorodeoxyglucose positron emission tomography and iodine-131 whole-body scintigraphy in the follow-up of differentiated thyroid cancer

Metastases of differentiated thyroid cancer may show different uptake patterns for fluorine-18 fluorodeoxyglucose and [¹³¹I]NaI. FDG positron emission tomography (PET), iodine-131 whole-body scintigraphy (¹³¹I WBS) and magnetic resonance imaging were performed in 58 unselected patients, and spiral computed tomography (CT) of the lung in 25 patients. Thirty-eight patients presented with papillary carcinomas, 15 patients with follicular carcinomas and five patients with variants of follicular carcinoma. Primary tumour stage (pT) was pT1 in 3, pT2 in 19, pT3 in 11 and pT4 in 25 cases. For the detection of metastases, FDG PET was found to have a sensitivity of 50%, ¹³¹I WBS a sensitivity of 61%, and the two methods combined a sensitivity of 86%. When FDG PET was limited to patients with elevated thyroglobulin (Tg) levels and negative ¹³¹I WBS, the sensitivity of this algorithm was 82%. Of the 21 patients with lymph node metastases, seven presented with FDG uptake but no iodine uptake. In four of them, a second FDG hot spot appeared in a lymph node metastasis of normal size. Five of the seven patients underwent surgery. None of the eight patients with pulmonary metastases smaller than 1 cm exhibited FDG uptake, while five of them had iodine uptake. All had positive results on spiral CT. In conclusion, FDG PET cannot be substituted for ¹³¹I WBS. If the Tg level is elevated and ¹³¹I WBS is negative, FDG PET can be used to detect lymph node metastases and complements anatomical imaging. A spiral CT of the lung is useful to exclude pulmonary metastases before planning a dissection of iodine-negative lymph node metastases. Received 2 May and in revised form 8 July 1997     

Combined PET/CT in the follow-up of differentiated thyroid carcinoma: what is the impact of each modality?

Purpose ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is a well-established method in the follow-up of patients with differentiated thyroid carcinoma (DTC), elevated thyroglobulin (Tg) and negative ¹³¹I scans. This retrospective clinical study was designed to evaluate the impact of computed tomography (CT) and that of FDG-PET in combined FDG-PET/CT examinations on the restaging of DTC patients. Methods Forty-seven FDG-PET/CT scans of 33 patients with a history of DTC, elevated Tg levels and negative ¹³¹I uptake or additionally suspected ¹³¹I-negative lesions were studied. PET and CT images were analysed independently by an experienced nuclear medicine specialist and a radiologist. Afterwards a final consensus interpretation, the gold standard in our department, was provided for the fused PET/CT images and, if available, for supplementary investigations. Results Thirty-five investigations (74%) revealed pathological FDG-PET/CT findings. In summary, 25 local recurrences, 62 lymph node metastases and 122 organ metastases (41 lung, 60 bone, 21 other organs) were diagnosed. In 36 out of 47 examinations (77%), the original PET diagnoses were modified in the final consensus interpretation owing to the CT assessments. In 8 of the 35 pathological FDG-PET/CT examinations (23%), the final consensus interpretation of the PET/CT images led to an alteration in the treatment plan. Conclusion PET/CT is a powerful fusion of two pre-existing imaging modalities, which not only improves the diagnostic value in restaging DTC patients with elevated Tg and negative ¹³¹I scan, but also provides accurate information regarding subsequent treatment options and may lead to a change in treatment management.     

Radioiodine-131 in differentiated thyroid cancer: a retrospective analysis of an uptake-related ablation strategy

In our hospital, a 24-h radioiodine-131 (¹³¹I) uptake-related ablation strategy is used in patients with differentiated thyroid cancer to destroy thyroid remnants after primary surgery. In this strategy, low doses of ¹³¹I are used, but data in the literature on its efficacy are conflicting. Therefore, we performed the present study to evaluate the clinical outcome of this ablation strategy. In this study, patients (n=235) were selected who underwent thyroidectomy for differentiated thyroid cancer, followed by an ablative dose of ¹³¹I. Approximately 6 months after ablation, treatment efficacy was evaluated using radioiodine scintigraphy and thyroglobulin (Tg) measurements. Successful ablation was defined as the absence of radioiodine uptake in the neck region (criterion 1). Tg values were determined 3–12 months after ablation (criterion 2). Based on criterion 1, unsuccessful ablation was found in 43.0% of cases. Pre-treatment uptake values were statistically significantly lower (P=0.003) in successfully ablated patients (mean 5.4%) than in unsuccessfully ablated patients (mean 8.2%). Based on criterion 2, unsuccessful ablation was found in 52.4% of patients. The uptake-related ablation strategy, using low doses of ¹³¹I, shows a relatively high treatment failure rate. Based on these results it is suggested that a lower ablation failure rate could be achieved by applying higher ¹³¹I doses in the ablation of thyroid remnants in differentiated thyroid carcinoma patients. In the case of lymph node metastases a further dose adjustment may be advisable.     

^131I治疗分化型甲状腺癌骨转移的疗效评价和生存分析

目的评价^131I治疗DTC骨转移的疗效及影响因素,评估生存率及其影响因素。方法回顾分析经^131I治疗的106例DTC骨转移患者的临床资料,分别基于^131I治疗后血清Tg的变化、骨痛缓解情况和影像学变化评价^131I治疗疗效,并对影响^131I疗效的因素进行单因素分析;采用寿命表法评估DTC骨转移患者的^131I治疗后总生存率;采用Kaplan—Meier法对影响生存率的因素进行分析,应用Log-rank法比较各组间差异。结果经^131I治疗后血Tg显著下降者37例,有效率34．9％。骨转移伴疼痛的61例DTC经^131I治疗后疼痛明显缓解者39例,有效率63．9％。患者年龄、病理类型、是否合并其他非骨性远端转移等因素对^131I治疗后血Tg的变化有影响（x2=6．443,11．455和6．756,P均〈0．05）,但对^131I治疗后骨痛缓解的影响无统计学意义（x2=0,0,0．060,P均〉0．05）。^131I治疗后77．4％的患者骨转移灶无明显影像学变化。该组DTC骨转移患者5年和10年生存率分别为86．47％和57．90％;骨转移灶数目、是否合并其他远端脏器转移、^131I治疗前是否行手术治疗对患者的10年生存率影响差异有统计学意义（Log-rank值为4．05,5．98和4．22,P均〈0．05）;患者的性别、年龄、病理类型、是否以骨转移症状首诊等因素对10年生存率无明显影响（Log—rank值为0．01,1．56,2．59和0．04,P均〉0．05）。结论^131I治疗可使DTC骨转移患者血清Tg下降、骨痛缓解、病灶保持稳定或缩小,是治疗DTC骨转移的有效手段;单发病灶、单纯骨转移、手术＋^131I治疗患者预后较好。     

Value of the first serum thyroglobulin level after total thyroidectomy for the diagnosis of metastases from differentiated thyroid carcinoma

The aim of this study was to evaluate the diagnostic significance of the first serum thyroglobulin (Tg) measurement, performed 40 days after total thyroidectomy for differentiated thyroid carcinoma and prior to the ablation of residual thyroid tissue by means of iodine-131 therapy. In a retrospective study we examined 334 consecutive patients followed up for 4–16 years by means of regular Tg measurements, ¹³¹I whole-body scans (WBS) and other diagnostic techniques, if necessary. In 79 patients metastases were discovered (32 lymph node and 47 distant metastases) within 18 months following thyroidectomy. Mean values of first Tg were significantly higher in patients with than in patients without metastases (258.9±310.6 vs 15.9±19.6 ng/ml; P<0.0001). Receiver operating characteristic (ROC) curve analysis of data revealed that for first Tg values higher than 69.7 ng/ml, the positive predictive value for the presence of metastases exceeded 90%. No statistically significant correlation was found between first Tg value and either thyroid-stimulating hormone (TSH) value or percentage of ¹³¹I uptake by residual thyroid tissue. No other parameter (age, histological type, site of metastases, ¹³¹I uptake by metastases) was significantly related to the first Tg value. We conclude that the first Tg measurement after total thyroidectomy provides a useful early diagnostic indication of metastatic disease in spite of the presence of a post-surgical thyroid remnant, and that this holds true regardless of the TSH value and WBS result. This early information is of clinical relevance for patient follow-up. Received 26 October 1998 and in revised form 12 June 1999     

Comparison of indium-111 octreotide and thallium-201 scintigraphy in patients mammographically suspected of having breast cancer: Preliminary results

Indium-111 octreotide and thallium-201 scintigraphic studies were compared in 21 patients (16 with palpable and five with non-palpable lesions) suspected of having breast malignancies on the basis of mammography. Early (15 min) and late (3 h)²⁰¹Tl (111 MBq) and 4-h and 24-h¹¹¹In-octreotide (111–148 MBq) static planar anterior images (matrix 256×256) were obtained on separate days. Images were evaluated both visually and quantitatively. Biopsy was performed following the imaging studies. Histopathology revealed 17 breast carcinomas (15 cases of invasive ductal carcinoma, one mucinous adenocarcinoma and one intraductal carcinoma) and four benign breast lesions (two fibroadenomas, one abscess and one case of fat necrosis). The means histopathologcial tumour size (mean largest diameter) was 3.38±1.9 cm.¹¹¹In-octreotide detected 16 of the 17 breast cancers (94%) while²⁰¹Tl detected 13 of them (76%). Both¹¹¹In-octreotide and²⁰¹Tl missed one nonpalpable carcinoma showing only an isolated cluster of microcalcifications on mammography. The smallest tumour size detected by both agents 1.5×1.5 cm. Of the four benign lesions, only the breast abscess revealed both²⁰¹Tl and¹¹¹In-octreotide uptake.¹¹¹In-octreotide scan also showed tracer uptake in five of the six patients with histologically proven axillary metastases, while four of these six patients showed²⁰¹Tl uptake. The tumour/background (T/B) ratios of late¹¹¹In-octreotide and²⁰¹Tl images were 1.71±0.38 and 1.46±0.30 respectively (P=0.039). In this preliminary study,¹¹¹In-octreotide yielded more favourable results than²⁰¹Tl in the detection of breast carcinomas. However, the diagnostic efficacy of¹¹¹In-octreotide imaging needs to be investigated in larger patient series.     

The role of somatostatin receptor scintigraphy in patients with pituitary adenoma or post-surgical recurrent tumours

To assess the role of scintigraphy with 111In-DTPA-D-Phe-octreotide (111In-octreotide) in the diagnosis of pituitary adenomas and in the evaluation of post-surgical recurrent or residual tumours, we performed scintigraphy with 111In-DTPA-D-Phe-octreotide (SRS) in 35 patients: 14 patients with confirmed pituitary tumours and 15 with confirmed recurrent tumours. Clinical, biochemical and histological analyses, conventional images (CT/MRI), and follow-up assessments during a period of 1 year to 4 years were recorded in all patients. In the present study, scintigraphy with 111In-octreotide showed positive uptake in 10 out of 14 patients with confirmed pituitary tumour and in 13 out of 15 patients with confirmed recurrent tumour, with an overall sensitivity of 79%. SRS showed better results in growth hormone (GH)- and prolactin (PRL)-secreting tumours (7/8 patients correctly identified) than in other adenomas (3/9). SRS detected recurrence of adenocorticotrophic hormone (ACTH)-secreting tumours (4/5 patients correctly identified) and non-secreting tumours (5/7 patients correctly identified). 111In-octreotide scintigraphy, in combination with other imaging modalities, is useful in the diagnosis and follow-up of pituitary tumours. It allows scar tissue to be differentiated from tumour recurrence after surgical treatment and ensures better selection of patients who will benefit from medical treatment with somatostatin analogues.     

The role of technetium-99m methoxyisobutylisonitrile scintigraphy in the planning of therapy and follow-up of patients with differentiated thyroid carcinoma after surgery

The aim of this study was to investigate the possible role of technetium-99m methoxyisobutylisonitrile (MIBI) scan in planning post-surgical therapy and follow-up in patients with differentiated thyroid carcinoma (DTC). Four groups of DTC patients were considered: Group 1 comprised 122 patients with high serum thyroglobulin (s-Tg) levels and negative high-dose iodine-131 scan during follow-up who had previously undergone total thyroidectomy and ¹³¹I treatment. Group 2 consisted of 27 patients who had previously undergone total thyroidectomy and ¹³¹I treatment but were now considered disease-free; this group was considered as controls. Group 3 comprised 49 patients studied after total thyroidectomy but prior to ¹³¹I scan. Finally, group 4 consisted of 21 patients who had previously undergone partial thyroidectomy alone. MIBI scan, neck ultrasonography (US), and s-Tg measurements during suppressive hormonal therapy (SHT) were obtained in all patients. Neck and chest computed tomography (CT) or magnetic resonance imaging (MRI) was also performed in group 1 patients. In group 1, MIBI scan and US were very sensitive in detecting cervical lymph node metastases (93.54% and 89.24%, respectively). Furthermore, MIBI scan and US played a complementary role in several patients, yielding a global sensitivity of 97.84%. In contrast, CT/MRI sensitivity for cervical lymph node metastases was very low (43.01%). MIBI scan also showed a higher sensitivity than CT/MRI in detecting mediastinal lymph node metastases (100% vs 57.89%). Regarding distant metastases, MIBI scan provided results similar to those of conventional imaging (CT, MRI, ^99mTc-methylene diphosphonate bone scan). In group 2, no false-positive cases were observed with MIBI scan (100% specificity). In group 3, MIBI scan correctly identified all the ¹³¹I-positive metastatic foci, except in two patients with micronodular pulmonary metastases that were visualised with ¹³¹I scan. In contrast, both MIBI scan and US showed low sensitivity (46.15% and 61.53%, respectively) compared with ¹³¹I scan in detecting thyroid remnants. s-Tg was increased in all patients with distant metastases but only in 56% of those with lymph node metastases. Furthermore, s-Tg was increased in 21.42% of patients with thyroid remnants alone (false-positive results). In group 4, MIBI scan was the only examination capable of detecting at an early stage a mediastinal lymph node metastasis in one patient. We conclude that the integrated MIBI scan/neck US protocol: (a) can be proposed as a first-line diagnostic procedure in the follow-up of DTC patients with high s-Tg levels and negative high-dose ¹³¹I scan, and (b) may be helpful in the follow-up of DTC patients who undergo partial thyroidectomy alone. Moreover, the combined MIBI scan/neck US/s-Tg protocol appears to be highly sensitive in identifying patients with metastatic disease after total thyroidectomy and prior to ¹³¹I scan; consequently, it may play a prognostic role in distinguishing high-risk from low-risk DTC patients. However, due to the low sensitivity of MIBI scan and neck US in detecting thyroid remnants, this diagnostic approach cannot be used as a predictor of ¹³¹I scan results. Lastly, because of the high sensitivity of MIBI scan and neck US in revealing both functioning and non-functioning metastases, this integrated protocol might be helpful in the follow-up of high-risk DTC patients, particularly for the early detection of lymph node metastases in patients with undetectable s-Tg during SHT. Received 21 October and in revised form 20 December 1999     

Comparison of whole-body <Superscript>18</Superscript>F-FDG PET, <Superscript>99m</Superscript>Tc-MIBI SPET,and post-therapeutic <Superscript>131</Superscript>I-Na scintigraphy in the detection of metastatic thyroid cancer

The usefulness of fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) in differentiated thyroid cancer (DTC) has been demonstrated by many investigators, but in only a small number of studies have FDG-PET images been compared with those obtained using other non-iodine tumour-seeking radiopharmaceuticals. In most of the studies, planar imaging was performed for comparison using thallium-201 chloride or technetium-99m 2-methoxyisobutylisonitrile (^99mTc-MIBI). Furthermore, FDG-PET studies were not always performed in the hypothyroid state with increased levels of thyroid stimulating hormone (TSH), which are known to increase FDG uptake by DTC. The aim of this study was to compare the ability of FDG-PET to detect metastatic DTC with that of ^99mTc-MIBI whole-body single-photon emission tomography (SPET) and post-therapeutic iodine-131 scintigraphy, evaluated under TSH stimulation. Nineteen patients (8 men, 11 women; age range, 38–72 years, mean 60 years; 17 thyroidectomised and 2 inoperable patients following ¹³¹I ablation of the remaining thyroid tissue; 16 papillary and 3 follicular carcinomas) with metastatic DTC underwent FDG-PET whole-body scan (WBS) and ^99mTc-MIBI SPET WBS at an interval of less than 1 week, followed by ¹³¹I therapy. The SPET images were reconstructed using the maximum likelihood expectation maximisation (ML-EM) method. All patients were hypothyroid at the time of each scan. ¹³¹I WBS was performed 3–5 days after oral administration of the therapeutic dose. A total of 32 lesions [10 lymph node (LN), 15 lung, 6 bone, 1 muscle] were diagnosed as metastases, as confirmed by histopathology and/or other imaging modalities (X-ray, US, CT, MRI, bone, ²⁰¹Tl and ¹³¹I scans). FDG-PET, ^99mTc-MIBI SPET and post-therapeutic ¹³¹I scintigraphy respectively revealed a total of 26 (81.3%), 20 (62.5%) and 22 (68.8%) lesions. These techniques respectively demonstrated nine (90.0%), eight (80.0%) and six (60.0%) LN metastases, and eleven (73.3%), seven (46.7%) and ten (66.7%) lung metastases. They each demonstrated five of the six bone metastases (83.3%). FDG-PET and ^99mTc-MIBI SPET were positive in 17 (78.3%) and 14 (63.6%) of the 22 ¹³¹I-positive lesions, respectively, and also in nine (90.0%) and six (60.0%) of the ten ¹³¹I-negative lesions, respectively. Three of the five ¹³¹I-positive and FDG-PET-negative lesions were miliary type lung metastases with a maximal nodular diameter of less than 10 mm. Comparison of FDG-PET with ^99mTc-MIBI SPET revealed concordant results in 24 lesions, and discordant results in eight lesions (seven with positive FDG-PET alone and one with positive ^99mTc-MIBI SPET alone). In conclusion: (a) even using whole-body SPET, FDG PET is superior to ^99mTc-MIBI in terms of ability to detect metastases of DTC; (b) the higher sensitivity of FDG-PET compared with the previous studies could partly be due to increased serum TSH.     

Indium-111 octreotide scintigraphy in neurofibromatosis

Scintigraphy with the radiolabelled somatostatin analogue indium-111-DTPA-D-Phe-l-octreotide has recently been proposed for the imaging of CNS neoplasms expressing somatostatin receptors. While meningiomas are imaged with high sensitivity, neurinomas do not take up octreotide owing to the lack of somatostatin receptors. Neurofibromatosis is a relatively uncommon disorder in which meningiomas and neurinomas often occur in the same patient. Differential diagnosis between these two tumours by computed tomography and magnetic resonance imaging can be difficult. This study reports on^{1 11}In-octreotide scintigraphy in four patients with neurofibromatosis.¹¹In-octreotide scintigraphy was shown to be very helpful in the in vivo differential diagnosis: all four meningiomas showed intense tracer uptake, while all 15 neurinomas were negative (P<0.001 by Fisher's exact test). It may be concluded that scintigraphy with¹¹¹In-octreotide is a useful diagnostic procedure in neurofibromatosis, complementing standard neuroradiological imaging procedures.     

The study of influence factors on 131I treatment of differentiated thyroid carcinoma with lymph node metastases

ObjectiveThyroid carcinoma is the most common malignant endocrine tumor, which comprises 1% in all human tumors. As for differentiated thyroid carcinoma (DTC), lymph nodes are the most common metastatic site for which the major treatment is ¹³¹I therapy. This retrospective study aimed to investigate the therapeutic effect and analyze the influence factors on ¹³¹I treatment of DTC with lymph node metastases.MethodsCollecting clinical data of 66 DTC patients with lymph node metastases at the Department of Nuclear Medicine, Xin Hua Hospital from January 1996 to January 2006. Investigating the therapeutic effect firstly and then dividing 66 patients into an eliminated group and an uneliminated group according to the evaluation criteria of the therapeutic effect. Finally, observing the differences between the two groups. The significant differences in the following 10 influence factors were determined: gender, age, pathological type, the periods from the thyroidectomy to the first ¹³¹I therapy, when the metastases were found, the history of resection of the lymph node metastases, the uptake of ¹⁸F-FDG in the lymph node metastases, remnant thyroid, multiple metastases, and the cumulative dose of ¹³¹I. This retrospective study was analyzed by Student t test, χ² test, and Fisher's exact test.ResultsOf all 66 patients with lymph node metastatic DTC treated by ¹³¹I therapy, 31 patients (46.97%) had complete elimination. Twenty-seven patients were improved or controlled, and the overall effective rate reached 87.88%. The elimination rate of lymph node metastases in patients with resection was significantly higher than in those without resection (χ²=5.561, P=.018<0.05). The elimination rate of lymph node metastases in patients with ¹⁸F-FDG uptake was significantly higher than in those without ¹⁸F-FDG uptake (χ²=4.014, P=.045<.05). There was no significant difference in the elimination rate among the patients with various values in the other eight factors.Conclusions¹³¹I Therapy is an effective treatment of lymph node metastatic DTC. The history of resection of the lymph node metastases and the uptake of ¹⁸F-FDG in the lymph node metastases were the influence factors on the therapeutic effect, whereas the other eight factors were probably not.     

L-3-[123I]Iodo-alpha-methyltyrosine scintigraphy in carcinoid tumors: correlation with biochemical activity and comparison with [111In-DTPA-D-Phe1]-octreotide imaging.

Carcinoid tumors can produce serotonin (5-hydroxytryptamine) and catecholamines from the precursors tryptophan and tyrosine. Our aim was to evaluate the tyrosine analog L-3-[123I]iodo-alpha-methyltyrosine (IMT) in the detection and the determination of biochemical activity of these tumors in comparison with 111In-labeled [diethylenetriaminepentaacetic acid (DTPA)-D-Phe1]-octreotide (111In-octreotide) scintigraphy. METHODS: SPECT and planar whole-body imaging were performed 15 min after administration of 300 MBq IMT in 22 patients with metastatic carcinoid tumors. The number of lesions detected was compared with the number detected by 111In-octreotide scintigraphy. The size and intensity of uptake of all lesions were graded using a simple scoring system, yielding a total body uptake score for both tracers. These scores were compared (nonparametric correlation) with biochemical markers of serotonin and catecholamine metabolism. RESULTS: IMT SPECT detected only 63 of 145 lesions detected by 111In-octreotide imaging (43%). IMT SPECT performance was best in the liver (60% detection rate). Both IMT uptake and 111In-octreotide uptake scores correlated with markers of serotonin metabolism (respective values for urinary 5-hydroxyindoleacetic acid: r = 0.67 and 0.48, P < 0.001 and 0.05; for urinary serotonin: r = 0.56 and 0.40, P = 0.002 and 0.05; and for platelet serotonin: r = 0.57 and 0.45, P < 0.01 and 0.05). No correlation with adrenaline or noradrenaline metabolites was found. However, IMT uptake, but not 111In-octreotide uptake, correlated with dopamine metabolite excretion (homovanillic acid: r = 0.60, P < 0.05; and dopamine relative sum: r = 0.61, P < 0.05). IMT uptake was higher in patients with increased dopamine metabolite excretion (P = 0.05). CONCLUSION: IMT uptake can be demonstrated in carcinoid lesions, but the method detected only 43% of carcinoid lesions that were positive on 111In-octreotide scintigraphy. Uptake of both tracers is related to the serotonin secretory activity. However, IMT uptake, but not 111In-octreotide uptake, was related to tumor dopamine metabolism. These findings may be of interest in the metabolic targeting of carcinoids.     

Is empiric 131I therapy justified for patients with positive thyroglobulin and negative 131I whole-body scanning results?

The long-term monitoring of patients with differentiated thyroid carcinoma (DTC) is essential throughout the patient's life after total or nearly total thyroidectomy followed by 131I remnant ablation and thyroid hormone suppression of thyroid-stimulating hormone (TSH). Sensitive surveillance for DTC recurrences and metastases includes radioiodine diagnostic whole-body scanning (DWBS) and measurement of serum thyroglobulin (Tg) levels after endogenous or exogenous TSH stimulation. Serum Tg levels during thyroid hormone withdrawal usually are correlated well with the results of DWBS. In general, Tg levels undetectable by DWBS suggest complete remission, whereas detectable or elevated Tg concentrations are suggestive of the presence of 131I uptake in local or distant metastases. However, DTC patients with a positive Tg test and negative 131I DWBS results (Tg+ DWBS-) have been observed in follow-up studies. The management of these cases begets controversy. METHODS: We electronically searched Medline (1966-2004.3), Embase (1984-2003), the Cochrane Library (2004, 2nd edition), CNKI (1994-2004), and CBM-DISC (1978-2004). We also manually searched the Chinese Journal of Isotopes, Radiologia pratica, and the Chinese Journal of Endocrinology and Metabolism. RESULTS: Ten serial observations and 3 nonrandomized controlled trials were found. The available data showed that of 314 patients who were treated empirically with 131I, 194 (62%) of 314 displayed pathologic uptake in the thyroid bed, lung, bone, mediastinum, and lymph nodes. In studies with Tg-on and Tg-off data, 171 (63%) of 271 patients achieved a decrease in Tg. CONCLUSION: On the basis of data from recent studies, 131I therapy should be individualized according to clinical characteristics. More significantly, a decrease in Tg levels was achieved in 63% of DTC patients with Tg+ DWBS-, suggesting that 131I therapy does have a therapeutic effect when the Tg level is considered an index of tumor burden. The 62% positive posttherapy whole-body scanning results also indicated that a therapeutic dose of 131I could reveal approximately one half of previously undiagnosed lesions in some patients. Therefore, 131I therapy may be justified in patients with Tg levels of > 10 microg/L and DWBS- and who are at high risk of any recurrence.     

Prognostic value of an increase in the serum thyroglobulin level at the time of the first ablative radioiodine treatment in patients with differentiated thyroid cancer

Purpose The aim of this study was to assess the prognostic factors for treatment efficacy, and in particular the increase in serum thyroglobulin (Tg) level at the time of the first ablative radioiodine treatment, in patients with differentiated thyroid carcinoma (DTC).Methods A retrospective chart review was performed on 407 patients treated for DTC by total thyroidectomy and ¹³¹I ablation between 1995 and 2002, and examined 5–12 months later with diagnostic ¹³¹I whole-body scan and serum Tg measurement after thyroid hormone treatment withdrawal. At the time of the ablative radioiodine treatment, serum Tg level was determined just before ¹³¹I administration (TgD0) and 5 days later (TgD5); Tg variation was expressed as the ratio TgD5/TgD0. At the first post-ablation follow-up examination, unsuccessful ablation was defined by a Tg level 2 ng/ml and/or abnormal ¹³¹I uptake.Results Ablation was unsuccessful in 51 patients. Univariate analysis showed high TgD0 level, low TgD5/TgD0 ratio extrathyroidal invasion, ¹³¹I uptake in the neck (excluding the thyroid bed) during the ablative treatment and distant metastases to be significantly associated with unsuccessful ablation. On logistic multivariate analysis, TgD0 level <5 ng/ml and TgD5/TgD0 ratio 20 were independently associated with successful ablation. A receiver operating characteristic curve analysis determined that a TgD5/TgD0 ratio greater than 20 had a 97% positive predictive value for successful ablation. When both TgD0 and TgD5/TgD0 ratio were considered, that is, TgD0 <5 ng/ml or TgD0 5 ng/ml but TgD5/TgD0 ratio >20, ablation was unsuccessful in only 12/301 patients.Conclusion Our data show that the TgD5/TgD0 ratio may be used as a new prognostic indicator of ¹³¹I treatment efficacy in patients with DTC.     

Radio-guided surgery of differentiated thyroid cancer using (131)I or 99mTc-Sestamibi

The classical therapeutic approach to patients with differentiated thyroid cancer (DTC) is based on total or near-total thyroidectomy, followed by (131)I treatment and thyroid-stimulating hormone suppressive therapy. This approach allows complete cure in many patients, especially when the tumour is diagnosed at an early stage; it also allows long-term survival in patients with locoregional recurrences or distant metastases if they can be treated with (131)I. In contrast, when metastatic DTC deposits lose their ability to trap (131)I (non-functioning metastases), a worse prognosis is expected. Nevertheless, in patients with locoregional non-functioning recurrences, an early diagnosis and prompt surgical extirpation can lead to a favourable prognosis. In these cases, radical surgery is needed. This can be achieved with radio-guided surgery using a hand-held gamma probe and a tumour-seeking radiotracer to detect, intraoperatively, the smallest metastatic lesions. In this paper, we discuss the two principal techniques proposed in the literature for radio-guided surgery of non-functioning DTC metastatic recurrences, the first using high doses of (131)I and the second using low doses of 99mTc-Sestamibi.     

Value of technetium scintigraphy and iodine uptake measurement during follow-up of differentiated thyroid cancer

Measurement of serum thyroglobulin (Tg) levels and I-131 whole body scintigraphy (WBS) are used in the follow-up of patients with differentiated thyroid cancer (DTC). This study was designed to evaluate the significance of persistent I-131 uptake in the thyroid bed in patients with DTC following surgery and/or radioactive iodine ablation. Tc-99m thyroid scintigraphy (TS) and I-131 thyroid uptake (IU) were also performed to determine their clinical impact on patient management. PATIENTS AND METHODS: Sixty-two non-metastatic patients (14 men, 48 women) with a mean age of 44 years (range: 16-75) who had undergone surgical thyroidectomy for DTC were evaluated prospectively. All patients had undergone technetium and iodine scintigraphy (IS). Although serum Tg levels were measured in all patients, IU was available in 36. RESULTS: Tg values were in the range of 0.2-24 ng/ml (median: 0.2 ng/ml) when patients were in the hypothyroid state. I-131 WBS detected residual tissue in the neck in 30 patients (48%); however TS was positive in only 12 (19%). I-131 uptake in the thyroid bed ranged from 0 to 14% (median: 0.1%). Twelve of 13 patients with positive IS and negative TS had uptake values < or = 0.3% (p < 0.00001). When IU values were < or = 0.3%, 54% of our patients did not have any uptake in the thyroid bed on TS or IS, whereas when IU was > 0.3%, 80% of patients had neck uptake on both TS and IS (p < 0.00001). CONCLUSION: The results of this study demonstrate that the concordance of IS and TS depends on the IU level after suspension of replacement therapy. Measurements of IU and TS are of considerable value in evaluating patient response to therapy and will substantially reduce the need for repetitive radioiodine scans and unnecessary treatment doses in patients with undetectable Tg values.