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Thyrotoxicosis, an excess of circulating thyroid hormone, is a common presentation of thyroid benign disease. Thyroid cancer, particularly papillary carcinoma, has a global annual incidence of 5.4% in men and 6.5% in women. It is important to be aware of the possibility of co-existing thyroid cancer in thyrotoxic patients, as the cancers are often small. Radionuclide imaging can help discover non-palpable potentially cancerous nodules, and early treatment of thyroid cancer has a significant survival benefit. The guidelines for the treatment of thyrotoxicosis should reconsider the value of thyroid scintigraphy at the initial presentation in patients with no palpable nodules. [Extracted from the article]

Aim: [123I]Ioflupane (DaTSCAN) has a high binding affinity to the dopamine (DA) transporter (DaT) and tenfold less affinity to serotonin (5-HT) transporter (SERT). Both neurotransmitters are considered to contribute to body weight regulation. This study assesses the association between body mass index (BMI) and DaTSCAN availability in brain. Method: Scans from 74 consecutive patients who had undergone DaTSCAN single-photon emission computed tomography–computed tomography (SPECT-CT) were used to obtain semi- and absolute quantitative data in several volumes of interest (VOIs). Relative semi-quantitative specific binding ratios (SBRs) from Chang attenuated SPECT were obtained from GE DaTQUANT. Absolute normalised concentration (NC) was calculated from attenuation/scatter corrected SPECT-CT images, using an adapted version of the EARL Ltd (European Association of Nuclear Medicine (EANM) Research 4 Life) template. Scans were subdivided into either degenerative parkinsonism (abnormal = 49), borderline (n = 14) or scan without evidence of dopaminergic deficit (SWEDD = 11) using visual assessment and SBR values by two nuclear medicine consultants. Results: SBRs did not correlate with BMI. However, NC values correlated negatively in the entire cohort, with the strongest correlation in the frontal (r = − 0.649. p = 0.000), occipital (r = − 0.555, p = 0.000) regions and pons (r = − 0.555, p = 0.000). In the abnormal (n = 49) and SWEDD group (n = 11), NC of the frontal region was the most correlated with BMI (r = − 0.570, p = 0.000; r = − 0.813, p = 0.002, respectively). In the borderline group (n = 14), the left posterior putamen displayed the strongest correlation (r = − 0.765, p = 0.001). Conclusion: Absolute NC values demonstrate a strong inverse correlation with BMI, strongest in the extrastriatal regions. Due to the predominately non-overlapping distribution of DaT and SERT, this study suggests greater involvement of SERT in obesity with possible interplay with DA transmission. [ABSTRACT FROM AUTHOR]

Purpose: To compare qualitative and semi-quantitative PET/CT criteria, and the impact of nodule size on the diagnosis of solitary pulmonary nodules in a prospective multicentre trial. Methods: Patients with an SPN on CT ≥ 8 and ≤ 30 mm were recruited to the SPUTNIK trial at 16 sites accredited by the UK PET Core Lab. Qualitative assessment used a five-point ordinal PET-grade compared to the mediastinal blood pool, and a combined PET/CT grade using the CT features. Semi-quantitative measures included SUVmax of the nodule, and as an uptake ratio to the mediastinal blood pool (SURBLOOD) or liver (SURLIVER). The endpoints were diagnosis of lung cancer via biopsy/histology or completion of 2-year follow-up. Impact of nodule size was analysed by comparison between nodule size tertiles. Results: Three hundred fifty-five participants completed PET/CT and 2-year follow-up, with 59% (209/355) malignant nodules. The AUCs of the three techniques were SUVmax 0.87 (95% CI 0.83;0.91); SURBLOOD 0.87 (95% CI 0.83; 0.91, p = 0.30 versus SUVmax); and SURLIVER 0.87 (95% CI 0.83; 0.91, p = 0.09 vs. SUVmax). The AUCs for all techniques remained stable across size tertiles (p > 0.1 for difference), although the optimal diagnostic threshold varied by size. For nodules < 12 mm, an SUVmax of 1.75 or visual uptake equal to the mediastinum yielded the highest accuracy. For nodules > 16 mm, an SUVmax ≥ 3.6 or visual PET uptake greater than the mediastinum was the most accurate. Conclusion: In this multicentre trial, SUVmax was the most accurate technique for the diagnosis of solitary pulmonary nodules. Diagnostic thresholds should be altered according to nodule size. Trial registration: ISRCTN - ISRCTN30784948. ClinicalTrials.gov - NCT02013063 [ABSTRACT FROM AUTHOR]

Purpose: Multidrug resistance (MDR) impedes cancer treatment. Two efflux transporters from the ATP-binding cassette (ABC) family, ABCB1 and ABCG2, may contribute to MDR by restricting the entry of therapeutic drugs into tumor cells. Although a higher expression of these transporters has been correlated with an unfavorable response to chemotherapy, transporter expression does not necessarily correlate with function. In this study, we characterized the pharmacological properties of [18F]AVT-011, a new PET radiotracer for imaging transporter-mediated MDR in tumors. Methods: AVT-011 was radiolabeled with 18F and evaluated with PET imaging in preclinical models. Transport of [18F]AVT-011 by ABCB1 and/or ABCG2 was assessed by measuring its uptake in the brains of wild-type, Abcb1a/b−/−, and Abcg2−/− mice at baseline and after administration of the ABCB1 inhibitor tariquidar (n = 5/group). Metabolism and biodistribution of [18F]AVT-011 were also measured. To measure ABCB1 function in tumors, we performed PET experiments using both [18F]AVT-011 and [18F]FDG in mice bearing orthotopic breast tumors (n = 7–10/group) expressing clinically relevant levels of ABCB1. Results: At baseline, brain uptake was highest in Abcb1a/b−/− mice. After tariquidar administration, brain uptake increased 3-fold and 8-fold in wild-type and Abcg2−/− mice, respectively, but did not increase further in Abcb1a/b−/− mice. At 30 min after injection, the radiotracer was > 90% in its parent form and had highest uptake in organs of the hepatobiliary system. Compared with that in drug-sensitive tumors, uptake of [18F]AVT-011 was 32% lower in doxorubicin-resistant tumors with highest ABCB1 expression and increased by 40% with tariquidar administration. Tumor uptake of [18F]FDG did not significantly differ among groups. Conclusion: [18F]AVT-011 is a dual ABCB1/ABCG2 substrate radiotracer that can quantify transporter function at the blood-brain barrier and in ABCB1-expressing tumors, making it potentially suitable for clinical imaging of ABCB1-mediated MDR in tumors. [ABSTRACT FROM AUTHOR]

Purpose: To summarise data with radium-223 dichloride (223RaCl2), a mechanism-mediated targeted alpha therapy (TAT), in metastatic castration-resistant prostate cancer (mCRPC) and to chart the development of TAT in mCRPC and in other tumour types. Methods: Literature for this systematic review was identified using a PubMed search: ("targeted alpha therapy" or "targeted alpha particle therapy") or (213-bismuth or bismuth-213 or 213Bi) or (225-actinium or actinium-225 or 225Ac) or (211-astatine or astatine-211 or 211At) or (212-lead or lead-212 or 212Pb) or (227-thorium or thorium-227 or 227Th) or (223-radium or radium-223 or 223Ra or alpharadin) and (malignancy or cancer). Results were limited to English-language publications in humans, with the article type "clinical trial". Results: Forty-one publications were included (30 from the literature search and 11 from manual searches/reviews). In clinical trials in mCRPC, 223RaCl2 monotherapy is well tolerated, with significantly longer overall survival than placebo and improved quality of life. Clinical trial data have been reinforced by findings from real-world studies. 223RaCl2 has also shown promise in other tumour types with bone metastases, including advanced breast cancer and advanced renal cell carcinoma (in combination with anti-vascular endothelial growth factor). Several astatine-211- and bismuth-213-labelled molecules have demonstrated anti-tumour activity and acceptable toxicity in other tumour types. Conclusions: 223RaCl2 has demonstrated "proof of concept" for use of TAT in cancer in clinical practice. The efficacy and safety of 223RaCl2 monotherapy have been demonstrated in mCRPC, and 223RaCl2 combination therapies are under investigation in various tumours. TAT has broad applicability across tumour types. [ABSTRACT FROM AUTHOR]

Purpose: REASSURE is a global, prospective, non-interventional study to assess long-term safety of radium-223 in patients with bone metastatic castration-resistant prostate cancer. Here we report an interim analysis of patients according to previous use of chemotherapy. Methods: Radium-223 was administered in routine clinical practice. Interim safety analysis was planned after enrolment of the first 600 patients. Patient characteristics and safety data by previous administration of chemotherapy (docetaxel and/or cabazitaxel) were investigated. Results: This interim analysis included 583 patients. Median duration of observation was 7 months (range, 0–20). Nineteen patients treated with concomitant chemotherapy were excluded, 564 (97%) were eligible for exploratory analysis according to prior use of chemotherapy; 190 (34%) had previously received and completed chemotherapy, and 374 (66%) had not. In the prior versus no prior chemotherapy group, a higher proportion of patients had an Eastern Cooperative Oncology Group performance status of ≥2 (22% vs 11%) and > 20 metastatic lesions (26% vs 15%), median alkaline phosphatase (162.0 vs 115.0 U/L) and prostate-specific antigen (132.0 vs 40.2 ng/mL) levels were higher, and a lower proportion completed 6 radium-223 injections (45% vs 63%). Drug-related treatment-emergent adverse events (TEAEs) occurred in 63 and 48%, and haematological drug-related TEAEs in 21 and 9% of patients who had or had not previously received chemotherapy. Four drug-related deaths were reported, all in the prior chemotherapy group. Conclusions: The short-term safety profile of radium-223 in routine clinical practice was comparable to other clinical studies, irrespective of prior chemotherapy use. Haematological TEAEs occurred more frequently in the prior chemotherapy group, presumably due to decreased bone marrow function as a consequence of more advanced disease and prior exposure to cytotoxic therapy. Patients who had not previously received chemotherapy appeared to have a lower burden of disease at baseline, and a lower proportion discontinued radium-223 treatment. [ABSTRACT FROM AUTHOR]

Purpose: We first assessed whether the pattern of referrals to a nuclear medicine clinic improved as experience with 223Ra-dichloride increased, and whether referral patterns affected patient outcomes, and second assessed the value of bone scintigraphy, total alkaline phosphatase (tALP) and lymphadenopathy as prognostic factors in patients receiving 223Ra-dichloride.Methods: A total of 57 patients eligible to receive 223Ra-dichloride over a 2-year period (March 2014 to March 2016) were retrospectively assessed and prospectively followed (median follow up 298 days). 223Ra-Dichloride was administered at 4-week intervals for a maximum of six injections. The numbers of patients in years 1 and 2 referred in relation to extent of bone disease (EOBD) category and overall survival (OS) were determined. The prognostic factors EOBD category, baseline tALP (tALPBL), tALP response, greatest percentage reduction in tALP from baseline in any treatment cycle (ALPmax; among patients with elevated ALPBL), and the presence of lymphadenopathy were assessed as predictors of OS.Results: The proportion of patients with EOBD1 was higher in year 2 than in year 1 (29% and 4%, respectively), and in year 2 there was a lower rate of symptomatic skeleton-related events, a higher proportion of patients completing six cycles, and longer (albeit nonsignificant) OS (p = 0.55). There were significant differences in OS between EOBD4 patients and those in all other groups and between EOBD1 and EOBD3 patients (p < 0.05). OS was longer in patients with normal tALPBL than in those with elevated tALPBL (p = 0.01), in ALP responders than in nonresponders (p < 0.05), and in patients without lymphadenopathy than in those with lymphadenopathy (p = 0.29). OS was correlated with ALPmax (r2 = 0.24).Conclusion: A collaborative multidisciplinary referrals pathway, together with increased experience with 223Ra-dichloride, led to improved outcomes. In patients with elevated tALPBL, tALP dynamics may be useful for monitoring response and predicting OS. Imaging and prognostic markers may therefore be of value for individualizing 223Ra-dichloride treatment and planning retreatment; however, further studies are required. [ABSTRACT FROM AUTHOR]

Effective combination antiretroviral therapy (cART) has lead to a significant reduction in the prevalence and incidence of central nervous system (CNS) HIV-associated brain disease, particularly CNS opportunistic infections and HIV encephalitis. Despite this, cognitive deficits in people living with HIV, also known as HIV-associated neurocognitive disorders (HAND) have become more prevalent in recent years. The pathogenesis of HAND is likely to be multifactorial, however recent evidence suggests that brain microglial activation is the most likely pathogenic mechanism. Recent developments in positron emission tomography (PET) brain neuroimaging using novel brain radioligands targeting a variety of physiological changes in the brains of HIV-positive individuals have improved our understanding of the mechanisms associated with the development of HAND. This review will highlight recent PET brain neuroimaging studies in the cART era, focusing on physiological and neurochemical changes associated with HAND in people living with HIV. [ABSTRACT FROM AUTHOR]

The article discusses nuclear medicine (NM) training and practice in Great Britain as of April 2016. Topics include the number of sites providing NM services of which the majority are National Health Service publicly funded hospitals, institutions and positron emission tomography centers (PET), NM training offered at the Royal College of Physicians and the Royal College of Radiologists, and NM training through a physician college pathway.

Objectives: Hepatic steatosis is common but less is known of the heterogeneity of hepatic fat distribution and its clinical significance. Our objective was to measure the regional variabilities within the liver of standardised uptake values (SUV) as potential markers of hepatic fat distribution heterogeneity. Methods: Twenty-four patients having routine, clinically indicated PET/CT with (18)F-FDG and a wide range of fatty liver severity were selected. Maximum SUV (SUVmax), average SUV (SUVave), both calculated using lean body mass, and CT density were measured in 12 × 2-cm diameter ROIs in each patient. SUVave was also measured over the left ventricular cavity (SUVLV). Mean values of SUV indices, their ratios with SUVLV, and CT density in the 12 ROIs were calculated. Regional variabilities of SUV indices were expressed as coefficients of variation (CV; standard deviation/mean). Body mass index (BMI) was estimated from height and body weight, and %body fat and lean body mass from height, weight and gender. Results: Mean SUVmax/SUVave correlated significantly with mean CT density (r = -0.51; p < 0.02). In contrast, mean SUVmax, mean SUVave and their ratios with SUVLV showed no correlation with CT density. Mean CT density correlated with weight (r = -0.59; p < 0.005), BMI (r = -0.57; p < 0.01) and %body fat (r = -0.49; p < 0.02). Corresponding correlation coefficients for mean SUVmax/SUVave were 0.74 (p < 0.001), 0.65 (p < 0.001) and 0.46 (p < 0.03). In contrast, mean SUVmax, mean SUVave and their ratios with SUVLV showed no correlation with BMI, weight and %body fat. The CV of SUVmax/SUVave (r = -0.67; p < 0.001), but not the CVs of SUVmax or SUVave, correlated with mean CT density. Conclusions: SUVmax/SUVave and CT density are markers of hepatic steatosis. The regional variability of SUVmax/SUVave may be a marker of hepatic fat distribution heterogeneity. The novel concept is introduced that hepatic fat distribution heterogeneity may be a marker of hepatic pathology and of clinical value, and deserves further exploration with texture analysis. [ABSTRACT FROM AUTHOR]

Purpose: To compare normalisation to blood glucose (BG) with scaling to hepatic uptake for quantification of tumour (18) F-FDG uptake using the brain as a surrogate for tumours.Methods: Standardised uptake value (SUV) was measured over the liver, cerebellum, basal ganglia, and frontal cortex in 304 patients undergoing (18) F-FDG PET/CT. The relationship between brain FDG clearance and SUV was theoretically defined.Results: Brain SUV decreased exponentially with BG, with similar constants between cerebellum, basal ganglia, and frontal cortex (0.099-0.119 mmol/l(-1)) and similar to values for tumours estimated from the literature. Liver SUV, however, correlated positively with BG. Brain-to-liver SUV ratio therefore showed an inverse correlation with BG, well-fitted with a hyperbolic function (R = 0.83), as theoretically predicted. Brain SUV normalised to BG (nSUV) displayed a nonlinear correlation with BG (R = 0.55); however, as theoretically predicted, brain nSUV/liver SUV showed almost no correlation with BG. Correction of brain SUV using BG raised to an exponential power of 0.099 mmol/l(-1) also eliminated the correlation between brain SUV and BG.Conclusion: Brain SUV continues to correlate with BG after normalisation to BG. Likewise, liver SUV is unsuitable as a reference for tumour FDG uptake. Brain SUV divided by liver SUV, however, shows minimal dependence on BG.Key Points: • FDG standard uptake value in tumours helps clinicians assess response to treatment. • SUV is influenced by blood glucose; normalisation to blood glucose is recommended. • An alternative approach is to scale tumour SUV to liver SUV. • The brain used as a tumour surrogate shows that neither approach is valid. • Applying both approaches, however, appropriately corrects for blood glucose. [ABSTRACT FROM AUTHOR]

Purpose: Fine-needle aspiration (FNA) has revolutionised the care of patients with thyroid nodules and is the initial investigation of choice. However, as a result of nondiagnostic (Thy1) and nonneoplastic (Thy2) specimens, it remains an imperfect sole solution with a range of sensitivities and a high inadequate ratio. Therefore the British Thyroid Association (BTA) guidelines recommend a second FNA immediately for Thy1 specimens and 3–6 months later for Thy2 specimens. Patients must be followed up to exclude malignancy. In this study we assessed the performance of MIBI scintigraphy for diagnosing thyroid malignancy and the cost-effectiveness of a combined FNA/MIBI investigative strategy for the management of thyroid nodules. Methods: The diagnostic performance of MIBI scintigraphy was calculated from a retrospective review of local data combined with a meta-analysis of the published literature. Decision tree analysis was used to calculate the cost-effectiveness of a combined FNA/MIBI investigative strategy compared to the BTA guidelines. Results: From 712 patients, the sensitivity, specificity, PPV and NPV of MIBI scintigraphy for the diagnosis of malignancy were 96 %, 46 %, 34 % and 97 %, respectively. MIBI-based strategies were more accurate and associated with lower cost per patient (£1,855/€2,125 vs. £2,445/€2,801) and lower cost per cancer diagnosed (£1,902/€2,179 vs. £2,469/€2,828) with negligible change in life expectancy. Conclusion: Due to its high NPV, MIBI scintigraphy can usefully exclude malignancy for Thy1 and Thy2 lesions. Its low specificity means MIBI scintigraphy cannot be recommended as a first-line investigation, but as a second-line investigation MIBI scintigraphy may lead to a lower rate of unnecessary thyroidectomies. Combined FNA/MIBI strategies are potentially cost-effective in the management of solitary or dominant thyroid nodules. [ABSTRACT FROM AUTHOR]

Purpose: To establish the potential for tumour heterogeneity in non-small cell lung cancer (NSCLC) as assessed by CT texture analysis (CTTA) to provide an independent marker of survival for patients with NSCLC. Materials and methods: Tumour heterogeneity was assessed by CTTA of unenhanced images of primary pulmonary lesions from 54 patients undergoing F-fluorodeoxyglucose (FDG) PET-CT for staging of NSCLC. CTTA comprised image filtration to extract fine, medium and coarse features with quantification of the distribution of pixel values (uniformity) within the filtered images. Receiver operating characteristics identified thresholds for PET and CTTA parameters that were related to patient survival using Kaplan-Meier analysis. Results: The median (range) survival was 29.5 (1-38) months. 24, 10, 14 and 6 patients had tumour stages I, II, III and IV respectively. PET stage and tumour heterogeneity assessed by CTTA were significant independent predictors of survival (PET stage: Odds ratio 3.85, 95% confidence limits 0.9-8.09, P = 0.002; CTTA: Odds ratio 56.4, 95% confidence limits 4.79-666, p = 0.001). SUV was not a significantly associated with survival. Conclusion: Assessment of tumour heterogeneity by CTTA of non-contrast enhanced images has the potential for to provide a novel, independent predictor of survival for patients with NSCLC. Key Points: • Computed tomography is a routine staging procedure in non-small cell lung cancer • CT texture analysis (CTTA) can quantify heterogeneity within these lung tumours • CTTA seems to offer a novel independent predictor of survival for NSCLC • CTTA could contribute to disease risk-stratification for patients with NSCLC [ABSTRACT FROM AUTHOR]

The authors focus on interventional nuclear medicine wherein treatment can be provided for benign and malignant pathology with the help of a simple intervention radionuclide. It is differentiated from interventional radiology in that it can use some aspect of physiology to locate the radiopharmaceutical within the target volume. Possible reasons why directly injected radiopharmaceuticals have not been implemented more widely are also addressed.

A letter to the editor is presented in response to the article "Combined Tc-methoxyisobutylisonitrile scintigraphy and fineneedle aspiration cytology offers an accurate and potentially costeffective investigative strategy for the assessment of solitary or dominant thyroid nodules," by A. Riazi and colleagues in the 2013 issue

A letter to the editor is presented in response to an article on the relationship between 18F-fluoride bone imaging and diet for tumor patients.