Glucagon increases energy expenditure independently of brown adipose tissue activation in humans.

AIMS: To investigate, for a given energy expenditure (EE) rise, the differential effects of glucagon infusion and cold exposure on brown adipose tissue (BAT) activation in humans. METHODS: Indirect calorimetry and supraclavicular thermography was performed in 11 healthy male volunteers before and after: cold exposure; glucagon infusion (at 23 °C); and vehicle infusion (at 23 °C). All volunteers underwent (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET)/CT scanning with cold exposure. Subjects with cold-induced BAT activation on (18)F-FDG PET/CT (n = 8) underwent a randomly allocated second (18)F-FDG PET/CT scan (at 23 °C), either with glucagon infusion (n = 4) or vehicle infusion (n = 4). RESULTS: We observed that EE increased by 14% after cold exposure and by 15% after glucagon infusion (50 ng/kg/min; p < 0.05 vs control for both). Cold exposure produced an increase in neck temperature (+0.44 °C; p < 0.001 vs control), but glucagon infusion did not alter neck temperature. In subjects with a cold-induced increase in the metabolic activity of supraclavicular BAT on (18)F-FDG PET/CT, a significant rise in the metabolic activity of BAT after glucagon infusion was not detected. Cold exposure increased sympathetic activation, as measured by circulating norepinephrine levels, but glucagon infusion did not. CONCLUSIONS: Glucagon increases EE by a similar magnitude compared with cold activation, but independently of BAT thermogenesis. This finding is of importance for the development of safe treatments for obesity through upregulation of EE.

The role of early ¹8F-FDG PET/CT in prediction of progression-free survival after 9°Y radioembolization: comparison with RECIST and tumour density criteria.

PURPOSE: This study evaluated the ability of (18)F-FDG PET/CT imaging to predict early response to (90)Y-radioembolization in comparison with contrast-enhanced CT (CECT) using RECIST and lesion density (Choi) criteria. Progression-free survival (PFS) in patients with liver metastases at 2 years and decline in tumour markers were the primary end-points of the study. METHODS: A total of 121 liver lesions were evaluated in 25 patients (14 men, 11 women) with liver-dominant metastatic colorectal cancer who underwent (18)F-FDG PET/CT and CECT before and 6-8 weeks after treatment. Changes in SUV(max), tumour density measured in terms of Hounsfield units and the sum of the longest diameters (LD) were calculated for the target liver lesions in each patient. The patient responses to treatment were categorized using EORTC PET criteria, tumour density criteria (Hounsfield units) and RECIST, and were correlated with the responses of tumour markers and 2-year PFS using Kaplan-Meier plots and the log-rank test for comparison. Multivariate proportional hazards (Cox) regression analysis was performed to assess the effect of relevant prognostic factors on PFS. RESULTS: Using (18)F-FDG PET/CT response criteria, 15 patients had a partial response (PR) and 10 patients had stable disease (SD), while using RECIST only 2 patients had a PR and 23 had SD. Two patients had a PR, 21 SD and 2 progressive disease using tumour density criteria. The mean changes in SUV(max), sum of the LDs and tumour density after treatment were 2.9 ± 2.6, 7.3 ± 14.4 mm and 1.9 ± 13.18 HU, respectively. Patients who had a PR on (18)F-FDG PET/CT had a mean decrease of 44.5 % in SUV(max) compared to those with SD who had a decrease of only 10.3 %. The decreases in SUV(max) and sum of the LDs were significant (p < 0.0001, p < 0.05, respectively) while the decrease in tumour density was not (p > 0.1065). The responses on the (18)F-FDG PET/CT studies were highly correlated with the responses of tumour markers (p < 0.0001 for LDH, p = 0.01 for CEA and p = 0.02 for Ca19-9), while the responses on the CECT studies using both RECIST and tumour density criteria were not significantly correlated with the responses of tumour markers. The responses on (18)F-FDG PET/CT studies also significantly predicted PFS (the median PFS in those with a PR was 12.0 months and in those with SD was 5 months, p < 0.0001), while RECIST and tumour density did not significantly predict PFS. Multivariate analysis demonstrated that responses on (18)F-FDG PET/CT studies and decreases in SUV(max) of ≤ 2.0 were the strongest predictors of PFS. CONCLUSION: Early response assessment to (90)Y-radioembolization using (18)F-FDG PET/CT is superior to RECIST and tumour density, demonstrating a correlation with tumour markers and significantly predicting PFS in patients with liver metastases. This could enable early response-adapted treatment strategies to be employed.

A comparison of the performance of 68Ga-DOTATATE PET/CT and ¹²³I-MIBG SPECT in the diagnosis and follow-up of phaeochromocytoma and paraganglioma.

PURPOSE: To compare the sensitivity of (123)I-metaiodobenzylguanidine (MIBG) SPECT and (68)Ga-DOTATATE PET/CT in detecting phaeochromocytomas (PCC) and paragangliomas (PGL) in the initial diagnosis and follow-up of patients with PCC and PGL disease. METHODS: Retrospective analysis of 15 patients with PCC/PGL who had contemporaneous (123)I-MIBG and (68)Ga-DOTATATE imaging. RESULTS: Of the 15 patients in the series, 8 were concordant with both modalities picking up clinically significant lesions. There were no patients in whom both modalities failed to pick up clinically significant lesions. There was discordance in seven patients: 5 had positive (68)Ga-DOTATATE and negative (123)I-MIBG, and 2 (12 and 14) had negative (68)Ga-DOTATATE and positive (123)I-MIBG. Utilizing (123)I-MIBG as the gold standard, (68)Ga-DOTATATE had a sensitivity of 80 % and a positive predictive value of 62 %. The greatest discordance was in head and neck lesions, with the lesions in 4 patients being picked up by (68)Ga-DOTATATE and missed by (123)I-MIBG. On a per-lesion analysis, cross-sectional (CT and MRI) and (68)Ga-DOTATATE was superior to (123)I-MIBG in detecting lesions in all anatomical locations, and particularly bony lesions. CONCLUSION: First, (68)Ga-DOTATATE should be considered as a first-line investigation in patients at high risk of PGL and metastatic disease, such as in the screening of carriers for mutations associated with familial PGL syndromes. Second, if (123)I-MIBG does not detect lesions in patients with a high pretest probability of PCC or PGL, (68)Ga-DOTATATE should be considered as the next investigation. Third, (68)Ga-DOTATATE hould be considered in preference to (123)I-MIBG in patients in whom metastatic spread, particularly to the bone, is suspected.

In high risk hypertensive subjects with incidental and unilateral renal artery stenosis percutaneous revascularization with stent improves blood pressure control but not glomerular filtration rate.

AIM: In high-risk hypertensive subjects (HTs) with incidental unilateral renal artery stenosis (RAS), the effectiveness of percutaneous revascularization with stent (PR-STENT) on blood pressure (BP) and glomerular filtration rate (GFR) is not established. METHODS: Eighteen HTs aged 65.7 ± 9.2 years with angiographically diagnosed unilateral RAS (≥ 60%) were randomized to receive PR-STENT (N=9) or to NO-STENT (N=9). BP (mercury sphygmomanometer) and GFR (99mTc-DTPA clearances during renal scintigraphy) were evaluated yearly for three years. Echo-Doppler of renal arteries was performed to verify the anatomic patency and flow velocities of the reperfused artery. Analysis of variance compared BP and GFR values changes from baseline to the follow-up; differences for continuous variables were evaluated between groups with the Tukey's post hoc test after adjustment for age, change of BP between baseline and at the follow-up, GFR and body mass index (BMI). RESULTS: Baseline systolic BP and GFR values were not different between groups. The significantly greater GFR increase observed in PR-STENT than in NO-STENT at univariate analysis at the end of follow-up (62.5 ± 19.2 vs. 42.24 ± 17.6, P<0.02) disappeared after adjustment for confounding factors. However, systolic BP remained significantly lower in PR-STENT than in NO-STENT (140.1 ± 4.6 vs. 170.0 ± 8.3, P<0.0001) also after adjustment for age, GFR and BMI. CONCLUSION: PR-STENT reduces systolic BP without improving GFR. Due to the strong association between high BP and renal damage, this study raises the question on whether PR-STENT should be performed in all HTs with unilateral and incidental RAS.

Functional assessment in the multimodality imaging of pancreatic neuro-endocrine tumours.

Pancreatic neuroendocrine tumours comprise a heterogeneous group that are rare but could result in serious manifestations. Surgical excision provides the best approach to treatment but many patients may have small lesions that are difficult to detect, or present with wide spread disease by the time of diagnosis. In addition to clinical assessment and biochemical tests, imaging is a major factor in establishing the diagnosis. Cross-sectional imaging such as US, CT and MR, play a major role in the initial assessment. However, they may miss small lesions or metastatic spread. Functional Imaging became possible with the development of somatostatin receptor imaging using 111In-octreotide, which when combined with anatomical imaging could provide enhanced detection. A major improvement has been achieved by combining receptor and PET inaging through the use of 68Ga-DOTA complexes that have been shown to have a much better sensitivity than other imaging modalities and can provide the basis for radionuclide treatment with 90Y or 177Lu labelled with DOTA complexes.

Endocrine tumors: the evolving role of positron emission tomography in diagnosis and management.

Endocrine tumors comprise a range of benign and malignant conditions that produce a spectrum of clinical symptoms and signs depending on the specific hormones they produce. The symptoms and presentations of these tumors are often independent of their size and location. Because of their expression of cell membrane receptors or production of specific types of hormones or peptides, endocrine tumors can be identified with functional radionuclide imaging much more readily compared to standard cross-sectional imaging. In recent years, 18F-fluoro-deoxy- D-glucose positron emission tomography (18F-FDG-PET) has emerged as a useful tool for diagnosing and assessing many tumors. In this review we describe how PET, using 18F-FDG and other radiopharmaceuticals can be useful in the diagnosis and management of a wide range of endocrine tumors.

Multiorgan dysfunctions in diabetic patients: the role of functional imaging.

Functional imaging plays a central role in the evaluation of some of the clinical problems faced by diabetic patients. In cardiovascular disease, myocardial perfusion imaging, particularly when complemented by gated SPECT, is a powerful tool not only for establishing the diagnosis of coronary artery disease, but also for providing prognostic information in both the general and diabetic populations. Although promising, its role in screening of asymptomatic diabetic patients is yet to be established, and its role as a potential 'one-stop shop' also needs further study. PET is currently the gold standard for viability assessment, and also provides prognostic data, but its widespread use is limited by cost and availability. Hybrid imaging with PET/CT is promising, and could revolutionise cardiac imaging by combining functional and anatomic information. In the investigation of the diabetic foot, labelled leukocyte imaging is the nuclear medicine test of choice to diagnose osteomyelitis. It is likely that SPECT/CT will further improve diagnostic accuracy, but more studies are needed. Combined leukocyte and bone marrow imaging is of value in distinguishing osteomyelitis from neuropathic osteoarthropathy in the diabetic foot; PET and PET/CT may also be of value in these cases, but their wider role is currently inconclusive. The value of bone scintigraphy in the diabetic foot, even as a screening test, is questionable. Functional imaging methods can also be employed in the evaluation of other diabetic complications, including the assessment of left ventricular function, renal scarring and gastric emptying, but these methods are not widely used in current clinical practice.

Multimodality imaging of the parathyroid glands in primary hyperparathyroidism.

Primary hyperparathyroidism is a common endocrine disorder, affecting approximately 1 in 500 women and 1 in 2,000 men. Surgical removal of the hyperfunctioning parathyroid gland is the primary curative treatment. The last decade has witnessed the development of minimally invasive parathyroidectomy, which is based on the fact that the vast majority of cases are caused by single adenomas. However, the success of this technique relies on accurate preoperative localisation of the parathyroid lesions. The imaging modalities used vary at different institutions according to local expertise and availability, but include high resolution ultrasound, radionuclide studies, computed tomography (CT) and magnetic resonance imaging (MRI). Ultrasound and 99mTc sestamibi scintigraphy, particularly when complemented by single photon emission computed tomography (SPECT), are currently the imaging techniques of choice for preoperative localisation of parathyroid adenomas; a combination of the two methods further improves the sensitivity and accuracy of detection. CT is less commonly used for preoperative localisation and usually reserved for cases of failed parathyroidectomy, for the detection of suspected ectopic glands. MRI appears to be useful in patients with persistent or recurrent hyperparathyroidism, who have previously undergone surgery. Cross-sectional imaging is also useful in cases where the findings at sonography and scintigraphy are discordant. SPECT/CT appears promising, but further studies are needed to evaluate its role in preoperative localisation.

PET imaging in endocrine tumours.

The role of PET in the assessment of endocrine tumours has been, until recently, restricted to the use of (18)F-fluoro-deoxy-D-glucose ((18)F-FDG). Being a marker of metabolically active lesions that show high grading and low differentiation, FDG is not ideal for this purpose since the majority of endocrine tumours are slow growing and highly differentiated. It is however useful when dedifferentiation takes place and provides excellent prognostic information. A number of hormone precursors and amino acids are labelled with (11)C and used successfully in the management of parathyroid, adrenal and pituitary tumours. However, the short half-life of (11)C radiopharmaceuticals restricts their use to centres with access to an on-site cyclotron, while the high cost of production may limit their use to research purposes. A promising new positron-emission tomography (PET) tracer is Gallium-68 obtained by elution from a long shelf-life generator that makes it economic and cyclotron-independent. Its short half-life and flexible labelling ability to a wide range of peptides and antibodies makes it ideal for PET imaging. In addition to imaging GEP-NETs and phaeochromocytoma, it has the potential to be used in a wider range of endocrine tumours.

Review. 18F-FDG PET in the diagnosis and follow-up of thyroid malignancy.

The diagnosis of carcinoma of the thyroid is usually made in the process of investigating a thyroid nodule with clinical examination, Technetium-99m scan, ultrasonography and fine-needle aspiration (FNA) cytology. The follow-up is mainly based on 123-iodine and 131-iodine scans and serum thyroglogulin measurement. The aim of the present review was to establish the role of 18F-FDG PET in the differential diagnosis of doubtful thyroid nodules and in the follow-up of patients with increased serum thyroglobulin levels and negative iodine-scan. It remains to be defined if metabolic imaging with PET could be a useful routine procedure in the management of thyroid tumours since the majority of them are well-differentiated and therefore have less avidity to 18F-FDG. In the present work we collected the specific literature derived from MEDLINE over the last 10 years to clarify the potential clinical value of 18F-FDG PET in thyroid malignancies. An emerging role for 18F-FDG PET is in the assessment of incidental finding of a thyroid nodule which, when showing high FDG uptake should be regarded as a possible malignancy that needs further assessment. Another well-documented role for 18F-FDG PET is in the investigation of cases of established well-differentiated thyroid carcinomas presenting with high thyroglobulin and negative iodine imaging. An increase of the 18F-FDG uptake in these tumours indicates a shift towards lesser differentiation (with more aggression and poor prognosis) and may benefit from alternative management. 18F-FDG PET can be considered a routine functional imaging method in detecting iodine-negative recurrent disease in thyroid cancer patients with elevated serum thyroglobulin levels during follow-up. 18F-FDG PET seems to be useful also in differential diagnosis of suspected thyroid nodules, especially using the semi-quantitative SUV analysis.

99mTc-sestamibi radio-guided surgery of loco-regional 131Iodine-negative recurrent thyroid cancer.

AIM: We report here our experience in a larger series of differentiated thyroid cancer (DTC) patients who had been treated by (99m)Tc-sestamibi radio-guided surgery (RGS) for (131)Iodine ((131)I)-negative loco-regional recurrent disease. METHODS: Fifty-eight patients with loco-regional (131)I-negative recurrent disease from DTC were studied with (99m)Tc-sestamibi directed RGS using a hand-held 11-mm gamma probe as an intra-operative detector. Patients were selected for RGS on the basis of (a) progressive increase of serum thyroglobulin (Tg) levels after first treatment during follow-up, (b) negative high dose (100 mCi, 3.7 GBq) (131)I whole-body scan, and (c) positive pre-operative (99m)Tc-sestamibi scintigraphy for the presence of loco-regional recurrent disease. There were 41 papillary (1 "tall" cell variant), 13 follicular and 4 Hürthle cells tumours. In 14 patients thyroid cancer recurred in the thyroid bed while cervical lymph node metastases were found in 37 patients, and 7 patients had recurrent disease both in the thyroid bed and in cervical lymph nodes. RESULTS: At bilateral neck exploration, 147 metastatic foci ranging from 4 mm to 51 mm in largest diameter (mean tumour diameter=17.3+/-9.5mm) were removed. Eighty-five of them (58%) had been pre-operatively identified at (99m)Tc-sestamibi scintigraphy. After RGS, serum Tg levels normalised in 43 of 58 patients (serum Tg<2 ng/ml--they were considered disease-free), serum Tg remained slightly increased in 12 patients without evidence of metastatic disease at scintigraphic and radiologic imaging (serum Tg<10 ng/mg--they were considered living with microscopic disease), while serum Tg significantly increased up to values>900 ng/ml in 3 patients who developed lung metastases. The mean lesion to background (99m)Tc-sestamibi uptake ratios decreased in all 58 patients (p<0.0001). Post-surgical follow-up ranged 6-72 months (mean+/-SD=29.6+/-13.5 months). The operating surgeon assessed RGS as very useful in 14 patients in whom metastatic foci were embedded in fibrotic tissues or located behind blood vessels, useful in 22 patients, moderately useful 17 patients and not useful in 5 patients. CONCLUSION: Our data suggest that a (99m)Tc-sestamibi intra-operative gamma probe can be used to identify and guide resection of recurrent loco-regional tumour in DTC patients with (131)I-negative loco-regional metastatic foci.

Clinical and imaging experience with yttrium-90 microspheres in the management of unresectable liver tumours.

INTRODUCTION: Selective internal radiation therapy (SIRT) is emerging as a new therapeutic modality in recent years for management of non-resectable hepatic malignancies. Our experience in clinical application of this treatment is reported here. MATERIAL AND METHODS: From June 2004, patients whose liver tumours were no longer amenable for any conventional treatment with either chemotherapy or surgery were considered for yttrium-90 microspheres treatment after discussion at our multidisciplinary meeting. A pre-treatment planning was carried out with visceral angiography and technetium-99m macroaggregated albumin (MAA) for assessment of both tumour volume and extrahepatic shunting in addition to a baseline PET and CT scans, respectively. Two weeks later, a second visceral angiogram was performed to deliver the calculated dosage of microspheres into the arterial system supplying the tumour. Patients were then followed up with tumour markers, repeat PET and CT scans of abdomen at 6 weeks and 3 monthly thereafter. RESULT: Twenty-one patients (F=11, M=10; age range 40-75 years, mean=58 years) received yttrium-90 microspheres consisting of liver metastases from colorectal primary (n=10) and non-colorectal primaries (n=8), and primary liver tumours (n=3). One patient received 2 treatments. The mean administered activity of microspheres delivered was 1.9 GBq (range 1.2-2.5 GBq). Injection of microspheres had no immediate effect on either clinical haematology or liver function tests. At follow-up, 86% of patients showed decreased activity on PET scan at 6 weeks (p=0.01). The mean pre-treatment SUV was 12.2+/-3.7 and the mean post-treatment SUV was 9.3+/-3.7, indicating a significant improvement measured with PET activity. Only 13% showed a reduction in the size of tumour on CT scan. For patients with colorectal liver metastases, there was no significant reduction in CEA level (127+/-115 vs 75+/-72 micro/l, p=0.39). Complications were seen in 4 patients (19%) including radiation hepatitis (n=2), cholecystitis (n=1) and duodenal ulceration (n=1). All resolved without surgical intervention. Seven patients died at follow-up from progressive extrahepatic disease (33%). CONCLUSION: SIRT should be considered for patients with advanced liver cancer. It has a significant effect on liver disease in the absence of extrahepatic disease. PET imaging has an integral role in the assessment of patients treated with yttrium-90 SIR-Spheres.

Gallium-68 PET: a new frontier in receptor cancer imaging.

Neuroendocrine tumours (NET) are rare tumours that occur most commonly in the GI tract. Various labelled somatostatin analogues are used to image NET expressing somatostatin receptors (SSTR). In traditional nuclear medicine, most peptides used in imaging NET have been labelled with indium-111, the commonest being indium-111-octreotide (111In-octreotide). Unfortunately, the unfavourable physical qualities of In-111 make it unsuitable for detecting small tumour deposits. The recent introduction of gallium-68-1,4, 7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (gallium-68-DOTA) compounds for positron emission tomography (PET) imaging has significantly improved the quality of imaging NET through improved resolution of PET and higher affinity of the new generation of peptides to SSTR. In the present paper, we discuss the clinical and research applications of PET radio-tracers for evaluating NET, in particular gallium-68-DOTA compounds. The recent introduction of PET imaging with gallium-68 has major bearings in current and future clinical practice. Its labelling with DOTA compounds has cleared the way for somatostatin receptor imaging with a viable PET agent, with all its inherent imaging advantages compared to single photon imaging. The pre-clinical and clinical applications of this technique has been successful in a variety of tumours, particularly NET and its labelling with other ligands and molecules will improve the management of other tumours and the assessment of infection.

Iodine-131 radio-guided surgery in differentiated thyroid cancer: outcome on 31 patients and review of the literature.

In the present study we investigated the role of radio-guided surgery with Iodine-131 (I-131) in a group of 31 patients with differentiated thyroid cancer (DTC) and loco-regional recurrent disease. The principal inclusion criterion for I-131 radio-guided surgery in our protocol was the presence of an I-131 positive loco-regional disease relapse after previous total thyroidectomy and at least 2 ineffective conventional I-131 treatments. The protocol we used consisted of the following steps. Day 0: all patients were hospitalized and received a therapeutic 3.7 GBq (100 mCi) dose of I-131 after thyroid hormone therapy withdrawal in condition of overt hypothyroidism (serum TSH levels>30 microUI/ml). Day 3: a whole body scan following the therapeutic I-131 dose (TxWBS) administration was acquired. Day 5: neck surgery was performed through a wide bilateral neck exploration using a 15-mm collimated gamma probe, measuring the absolute intra-operative counts and calculating the lesion to background (L/B) ratio. Day 7: post-surgery TxWBS was performed using the remaining radioactivity to evaluate the completeness of tumoral lesions extirpation. The final histologic examination showed the presence of 184 metastatic foci; among them, 98 (53.2%) were evident by both TxWBS and gamma probe evaluation, 76 (41.3%) were demonstrated only by gamma probe, and 10 (5.4%) were negative by both TxWBS and gamma probe evaluation. During follow-up (8 months to 4.9 years, mean 2.8 years), DxWBS, serum Tg levels off l-T4, and US showed absence of loco-regional disease in 25 patients (80.6%) while 6 patients had persistent disease. In conclusion, this protocol allowed us to identify neoplastic foci with high sensitivity and specificity, enabling us to remove loco-regional I-131 disease recurrences resistant to previous conventional I-131 therapies. Furthermore, the gamma probe allowed detection of some additional tumoral foci in sclerotic areas or located behind vascular structures that were not visualized at the pre-surgery TxWBS evaluation.

An unusual case of a solitary pulmonary nodule associated with an abscess correctly distinguished by Pet/Ct fusion imaging.

The case of a male patient affected by concomitant solitary pulmonary nodule and chest abscess located on the same side and each close to the other is reported. The importance in differential diagnosis of these two lesions obtained by the 18F-FDG PET/CT fusion imaging examination is discussed.

Treatment of primary and secondary liver tumours with selective internal radiation therapy.

When HCC is diagnosed at an early stage or liver is affected by a solitary metastasis they can be curable by surgical resection, but this may not be feasible when an extensive tumoural involvement is present. In these cases, possible non-surgical therapies include systemic chemotherapy, chemical ablation (ethanol or acetic acid), radiofrequency ablation, microwave ablation, cryotherapy and transarterial chemoembolisation. All the above mentioned treatments have advantages and disadvantages. In the present paper we reported our experience with selective internal radiation therapy (SIRT) of non-operable HCC and metastatic liver using 99Yttrium (99Y) radioactive microspheres, and our data are compared and discussed with those reported in the literature. A MEDLINE-based review of the literature has been made in the period between 1990 and April 2007. Detailed information on patients selection criteria, SIRT procedure, dose calculation, safety and adverse reactions, follow-up schedule, and clinical efficacy are provided. On the basis of our data, in agreement with those of the literature, SIRT has added another effective method for treatment of primary and secondary liver tumours, being successful in a large number of patients in different experiences. Moreover, SIRT is well tolerated and has minimal adverse effects. Despite being regarded as non-curative, it has been associated with improved survival, reduction in tumour marker, and regression in the number and size of lesions. Follow-up with imaging is essential to assess the response to therapy, and in this respect FDG PET has been shown to be more sensitive than CT, particularly in the early stages.

The role of sentinel lymph node biopsy in patients with differentiated thyroid carcinoma.

AIM: To evaluate the "state of art" of clinical role of sentinel lymph node (SLN) biopsy procedure in patients affected by differentiated thyroid carcinoma. METHODS: All papers cited on PubMed/MEDLINE until June 2005, published in English, and referred to the key words "sentinel lymph node biopsy" AND "thyroid carcinoma" OR "thyroid cancer" were reviewed for the purpose of the present study. RESULTS: The first method used for SLN biopsy in thyroid carcinoma patients was the vital blue dye technique. This technique had some disadvantages as: (a) risk of disruption of the lymphatic channels deriving from the thyroid cancer; (b) difficulty in disclosing SLN lying outside the central compartment; (c) parathyroid glands can take up blue dye and, thus, can be misinterpreted as lymph nodes. Some of the above cited disadvantages were overcome by using the lymphoscintigraphy and intraoperative gamma probe technique. A combination of the blue dye and gamma probe technique has also been proposed with synergic results. CONCLUSION: The reported advantages of the SLN biopsy in small differentiated thyroid carcinoma patients can be resumed as follows: (a) better selection of patients who would benefit from compartment oriented nodal dissection; (b) more accurate lymph node staging; (c) better selection of patients who can require (131)I treatment after surgery (SLN positive for metastasis); (d) better identification of SLN located out of the central compartment.

18F-FDG PET/CT fusion imaging in paediatric solid extracranial tumours.

This paper aims at discussing the utility of 18F-FDG PET/CT in the evaluation of paediatric solid extracranial tumours. Following a brief discussion of the basic principles and methodology of PET/CT system, it reviews the main characteristics of the tumours that can be visualised with 18F-FDG PET and presents examples of cases where the combined use of 18F-FDG PET/CT fusion imaging helped in the management of patients. It will also discuss the physiologic biodistribution of 18F-FDG, outlining the normal variants in the paediatric patients that may lead to misinterpretation.

Sentinel lymph node (SLN) procedure with patent V blue dye in 153 patients with papillary thyroid carcinoma (PTC): is it an accurate staging method?

The present study aims to evaluate the accuracy of sentinel lymph node (SLN) mapping performed by intratumoral injection of blue dye in a large series of patients with papillary thyroid cancer (PTC). 153 consecutive patients were enrolled in the study. All patients had a preoperative cytological diagnosis of PTC, and none had clinical or ultrasonographic (US) evidence of nodal involvement. At surgery, vital patent V blue dye was injected into the malignant thyroid nodule. Subsequently, total thyroidectomy, central compartment (CC) node dissection, and median inferior jugulocarotid node dissection of laterocervical compartment, ipsilateral to the primary tumour, were performed. The excised thyroid, the blue-positive SLN and blue-negative lymph nodes were sent for frozen section and definitive histophatologic analysis. At surgery, blue-positive SLN were found in 107/153 patients (69.9%), of whom 36 (33.6%) had micrometastasis in SLN; moreover, in 13 of these 36 patients (36.1%), other nodes were found to be metastatic. In the remaining 71/107 blue-positive SLN patients, both the SLN itself and the other removed nodes were found negative for the presence of metastatic disease. In 4 cases, a normal parathyroid gland and in 3 cases fibro-adipous tissue were blue-stained and mistakenly removed as SLN (7 false positive results). On the other hand, SLN was blue-negative in 46/153 patients (30.1%), of whom 7 patients (15.2%) had micrometastases in blue-negative lymph nodes. On the basis of these data, the blue dye procedure for SLN detection appears inappropriate as a standard of care in PTC due to a relatively high number of false negative and false positive results.

Evaluation of 18F-fluorothymidine positron emission tomography ([18F]FLT-PET/CT) methodology in assessing early response to chemotherapy in patients with gastro-oesophageal cancer.

BACKGROUND: 3'-Deoxy-3'-[18F]fluorothymidine ([18F]FLT) PET has limited utility in abdominal imaging due to high physiological hepatic uptake of a tracer. We evaluated [18F]FLT-PET/CT combined with a temporal-intensity information-based voxel-clustering approach termed kinetic spatial filtering (KSF) to improve tumour visualisation in patients with locally advanced and metastatic gastro-oesophageal cancer and as a marker of early response to chemotherapy. Dynamic [18F]FLT-PET/CT data were collected before and 3 weeks post first cycle of chemotherapy. Changes in tumour [18F]FLT-PET/CT variables were determined. Response was determined on contrast-enhanced CT after three cycles of therapy using RECIST 1.1. RESULTS: Ten patients were included. Following application of the KSF, visual distinction of all oesophageal and/or gastric tumours was observed in [18F]FLT-PET images. Among the nine patients available for response evaluation (RECIST 1.1), three patients had responded (partial response) and six patients were non-responders (stable disease). There was a significant association between Ki-67 and all baseline [18F]FLT-PET parameters. Area under the curve (AUC) from 0 to 1 min was associated with treatment response. CONCLUSIONS: The results of this study indicate that application of the KSF allowed accurate visualisation of both primary and metastatic lesions following imaging with the proliferation marker, [18F]FLT-PET/CT. However, [18F]FLT-PET uptake parameters did not correlate with response. Instead, we observe significant changes in tracer delivery following chemotherapy suggesting that further [18F]FLT-PET/CT studies in this tumour type should be undertaken with caution.