Factors affecting (223)Ra therapy: clinical experience after 532 cycles from a single institution.

PURPOSE: The aim of this study was to identify baseline features that predict outcome in (223)Ra therapy. METHODS: We retrospectively reviewed 110 patients with metastatic castration-resistant prostate cancer treated with (223)Ra. End points were overall survival (OS), progression-free survival (PFS), bone event-free survival (BeFS), and bone marrow failure (BMF). The following parameters were evaluated prior to the first (223)Ra cycle: serum levels of hemoglobin (Hb), prostate-specific antigen (PSA), alkaline phosphatase (ALP), Eastern Cooperative Oncology Group (ECOG) status, pain score, use of chemotherapy, and external beam radiation therapy (EBRT). During/after (223)Ra we evaluated: the total number of radium cycles (RaTot), the PSA doubling time (PSADT), and the use of chemotherapy, EBRT, abiraterone, and enzalutamide. RESULTS: A significant reduction of ALP (p < 0.001) and pain score (p = 0.041) occurred throughout the (223) Ra cycles. The risk of progression was associated with declining ECOG status [hazard ratio (HR) = 3.79; p < 0.001] and decrease in PSADT (HR = 8.22; p < 0.001). RaTot, ALP, initial ECOG status, initial pain score, and use of abiraterone were associated with OS (p ≤ 0.008), PFS (p ≤ 0.003), and BeFS (p ≤ 0.020). RaTot, ALP, initial ECOG status, and initial pain score were significantly associated with BMF (p ≤ 0.001) as well as Hb (p < 0.001) and EBRT (p = 0.009). On multivariable analysis, only RaTot and abiraterone remained significantly associated with OS (p < 0.001; p = 0.033, respectively), PFS (p < 0.001; p = 0.041, respectively), and BeFS (p < 0.001; p = 0.019, respectively). Additionally, RaTot (p = 0.027) and EBRT (p = 0.013) remained significantly associated with BMF. CONCLUSION: Concomitant use of abiraterone and (223)Ra seems to have a beneficial effect, while the EBRT may increase the risk of BMF.

Assessing the role of ¹8F-FDG PET and ¹8F-FDG PET/CT in the diagnosis of soft tissue musculoskeletal malignancies: a systematic review and meta-analysis.

PURPOSE: Twelve years ago a meta-analysis evaluated the diagnostic performance of (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in assessing musculoskeletal soft tissue lesions (MsSTL). Currently, PET/CT has substituted PET imaging; however, there has not been any published meta-analysis on the use of PET/CT or a comparison of PET/CT with PET in the diagnosis of MsSTL. Therefore, we conducted a meta-analysis to identify the current diagnostic performance of (18)F-FDG PET/CT and determine if there is added value when compared to PET. METHODS: A systematic review of English articles was conducted, and MEDLINE PubMed, the Cochrane Library, and Embase were searched from 1996 to March 2015. Studies exploring the diagnostic accuracy of (18)F-FDG PET/CT (or dedicated PET) compared to histopathology in patients with MsSTL undergoing investigation for malignancy were included. RESULTS: Our meta-analysis included 14 articles composed of 755 patients with 757 soft tissue lesions. There were 451 (60 %) malignant tumors and 306 benign lesions. The (18)F-FDG PET/CT (and dedicated PET) mean sensitivity, specificity, accuracy, positive predictive value, and negative predictive value for diagnosing MsSTL were 0.96 (0.90, 1.00), 0.77 (0.67, 0.86), 0.88 (0.85, 0.91), 0.86 (0.78, 0.94), and 0.91 (0.83, 0.99), respectively. The posterior mean (95 % highest posterior density interval) for the AUC was 0.92 (0.88, 0.96). PET/CT had higher specificity, accuracy, and positive predictive value when compared to a dedicated PET (0.85, 0.89, and 0.91 vs 0.71, 0.85, and 0.82, respectively). CONCLUSION: (18)F-FDG PET/CT and dedicated PET are both highly accurate in the diagnosis of MsSTL. PET/CT is more accurate and specific and has a higher positive predictive value than PET.

¹8F-Fluoride PET/CT is highly effective for excluding bone metastases even in patients with equivocal bone scintigraphy.

PURPOSE: Bone scintigraphy (BS) has been used extensively for many years for the diagnosis of bone metastases despite its low specificity and significant rate of equivocal lesions. (18)F-Fluoride PET/CT has been proven to have a high sensitivity and specificity in the detection of malignant bone lesions, but its effectiveness in patients with inconclusive lesions on BS is not well documented. This study evaluated the ability of (18)F-fluoride PET/CT to exclude bone metastases in patients with various malignant primary tumours and nonspecific findings on BS. METHODS: We prospectively studied 42 patients (34-88 years of age, 26 women) with different types of tumour. All patients had BS performed for staging or restaging purposes but with inconclusive findings. All patients underwent (18)F-fluoride PET/CT. All abnormalities identified on BS images were visually compared with their appearance on the PET/CT images. RESULTS: All the 96 inconclusive lesions found on BS images of the 42 patients were identified on PET/CT images. (18)F-Fluoride PET/CT correctly excluded bone metastases in 23 patients (68 lesions). Of 19 patients (28 lesions) classified by PET/CT as having metastases, 3 (5 lesions) were finally classified as free of bone metastases on follow-up. The sensitivity, specificity, and positive and negative predictive values of (18)F-fluoride PET/CT were, respectively, 100 %, 88 %, 84 % and 100 % for the identification of patients with metastases (patient analysis) and 100 %, 82 % and 100 % for the identification of metastatic lesions (lesion analysis). CONCLUSION: The factors that make BS inconclusive do not affect (18)F-fluoride PET/CT which shows a high sensitivity and negative predictive value for excluding bone metastases even in patients with inconclusive conventional BS.

Knee radiosynovectomy with 153Sm-hydroxyapatite compared to 90Y-hydroxyapatite: initial results of a prospective trial.

INTRODUCTION: Radiosynovectomy (RS) with 90Y-hydroxyapatite (90Y-HyA) aims to control knee hemarthrosis in hemophiliac patients to prevent secondary arthropathy. However, knee RS using 153Sm-hydroxyapatite (153Sm-HyA) is considered less suitable due to the lower average soft tissue range and energy of 153Sm for large joints, such as the knees. PURPOSE: The objective of this investigation was to assess the efficacy and safety of knee RS with 153Sm-HyA, compared to 90Y-HyA. METHODS: Forty patients were prospectively assigned to undergo knee RS with 153Sm-HyA (n = 19) or with 90Y-HyA (n = 21). The frequency of hemarthrosis episodes before and after treatment were compared. RESULTS: After six months of knee RS, 153Sm-HyA and 90Y-HyA promoted a similar reduction of hemarthrosis episodes (50% and 66.7%, respectively). However, after 12 months of knee RS, the reduction of hemarthrosis episodes was significantly (p = 0.037) higher using 153Sm-HyA (87.5%) compared to 90Y-HyA (50.0%). This discrepancy was more pronounced (p = 0.002) for 153Sm-HyA compared to 90Y-HyA in adults/adolescents. CONCLUSION: Knee radiosynovectomy with 153Sm-HyA is safe, reduces hemarthrosis episodes after 12 months of treatments, especially in adults/adolescents and even with grades III/IV arthropathy, similar to 90Y-HyA. 90Y-HyA seems to promote better hemarthrosis control in small children.

99mTc-sestamibi SPECT/CT and 18F-FDG-PET/CT have similar performance but different imaging patterns in newly diagnosed multiple myeloma.

PURPOSE: F-fluorodeoxiglucose (F-FDG)-PET/CT has been widely used to evaluate multiple myeloma. Tc-sestamibi (MIBI) scintigraphy has also been proposed for assessing multiple myeloma, but its use with state-of-the-art single-photon emission computed tomography/computed tomography (SPECT/CT) technology has not been fully evaluated.This study aimed to compare these two imaging modalities in multiple myeloma staging. MATERIALS AND METHODS: Sixty-two patients with recently diagnosed multiple myeloma were submitted to whole-body F-FDG-PET/CT and whole-body MIBI scans plus SPECT/CT of the chest and abdomen/pelvis. Number of focal lesions, contiguous soft tissue involvement (CSTI), extramedullary lesions (EMLs) and diffuse bone marrow (BM) involvement were recorded. RESULTS: PET/CT was positive in 59 patients (95%) and MIBI SPECT/CT in 58 (93%) (P = 0.69). MIBI detected more diffuse bone marrow involvement than PET/CT (respectively 78 vs. 58% of the patients), while PET/CT demonstrated more focal lesions than MIBI SPECT/CT (81 vs. 54% of the patients) (P = 0.002). PET/CT detected EMLs in four subjects and MIBI in one subject. CSTI was found in 28 (45%) and 23 (37%) patients on PET/CT and MIBI images, respectively (P = 0.36). Three patients with lytic lesions and no FDG uptake were MIBI positive, and two subjects with lytic lesions without MIBI uptake were FDG positive. CONCLUSION: MIBI SPECT/CT performs similarly to F-FDG-PET/CT in identifying sites of active disease in multiple myeloma staging. MIBI is more efficient than FDG for detecting the diffuse involvement of bone marrow but less efficient for detecting focal lesions. Some patients presented a 'mismatch' pattern of FDG/MIBI uptake.

Is True Whole-Body 18F-FDG PET/CT Required in Pediatric Lymphoma? An IAEA Multicenter Prospective Study.

Guidelines recommend true whole-body 18F-FDG PET/CT scans from vertex to toes in pediatric lymphoma patients, although this suggestion has not been validated in large clinical trials. The objective of the study was to evaluate the incidence and clinical impact of lesions outside the "eyes to thighs" regular field of view (R-FOV) in 18F-FDG PET/CT staging (sPET) and interim (iPET) scans in pediatric lymphoma patients. Methods: True whole-body sPET and iPET scans were prospectively obtained in pediatric lymphoma patients (11 worldwide centers). Expert panel central review of sPET and iPET scans were evaluated for lymphoma lesions outside the R-FOV and clinical relevance of these findings. Results: A total of 610 scans were obtained in 305 patients. The sPET scans did not show lesions outside the R-FOV in 91.8% of the patients, whereas in 8.2% patients the sPET scans demonstrated lesions also outside the R-FOV (soft tissue, bone, bone marrow, and skin); however, the presence of these lesions did not change the clinical stage of any patient and did not affect treatment decision. Among the 305 iPET scans, there were no new positive 18F-FDG-avid lesions outside the R-FOV, when compared with their paired sPET scans. A single lesion outside the R-FOV on iPET occurred in 1 patient (0.3%), with the primary lesion diagnosed in the femur on sPET that persisted on iPET. Conclusion: The identification of additional lesions outside the R-FOV (eyes to thighs) using 18F-FDG PET/CT has no impact in the definition of the clinical stage of disease and minimal impact in the treatment definition of patients with pediatric lymphoma. As so, R-FOV for both sPET and iPET scans could be performed.

Effect of thyroid-stimulating hormone in 68Ga-DOTATATE PET/CT of radioiodine-refractory thyroid carcinoma: a pilot study.

BACKGROUND: Radioiodine-refractory thyroid carcinomas (RAIRs) are characterized by reduced expression of sodium-iodine symporter, rising serum thyroglobulin levels, and negative whole-body radioiodine scans. Interestingly, RAIRs continue to express somatostatin receptors and can be identified with Ga-DOTATATE PET/CT imaging. OBJECTIVE: The objective of this study was to compare lesion detectability in Ga-DOTATATE PET/CT performed with elevated thyroid-stimulating hormone (eTSH) levels with suppressed thyroid-stimulating hormone (sTSH) levels. PATIENTS AND METHODS: Fifteen patients with RAIR were prospectively enrolled in this pilot study. All patients underwent two Ga-DOTATATE PET/CT studies: with sTSH and with eTSH (after 30 days of levothyroxine withdrawal). All studies were blindly evaluated for differences pertaining to maximum standardized uptake values, detection of local recurrence, cervical lymph node (LN) metastases, cervical levels involved, distant LN metastases, lung metastases, and bone metastases. Reference standard consisted of fluorine-18-fluorodeoxyglucose PET/CT imaging, neck ultrasound, biopsy, and follow-up. RESULTS: Ga-DOTATATE PET/CT performed with both sTSH or eTSH was highly sensitive (91-100%) for detecting RAIR metastases. Ga-DOTATATE PET/CT with eTSH detected a higher total number of lesions (P=0.002), higher rate of cervical and distant LN metastases (P=0.002 and 0.0313, respectively), and significantly higher maximum standardized uptake values for cervical and distant LN metastases (P=0.0010 and 0.0078, respectively) when compared with sTSH. CONCLUSION: Ga-DOTATATE PET/CT presents a high sensitivity in detecting metastatic lesions in patients with RAIR. Detectability increases with iodine-resistance, both with and without higher thyroid-stimulating hormone levels. These findings might improve staging and subsequent treatment planning, especially with radiolabeled somatostatin analogs.

18F-FDG PET/CT delayed images after diuretic for restaging invasive bladder cancer.

UNLABELLED: PET with (18)F-FDG has been considered of limited value for detection of bladder cancer because of the urinary excretion of the tracer. The purpose of this study was to investigate the role of PET/CT in the detection and restaging of bladder cancer using furosemide and oral hydration to remove the excreted (18)F-FDG from the bladder. METHODS: Seventeen patients with bladder cancer (11 without cystectomy, 6 with total cystectomy and urinary diversion) underwent (18)F-FDG PET/CT from head to the upper thighs 60 min after the intravenous injection of 370 MBq of (18)F-FDG. Additional pelvic images were acquired 1 h after the intravenous injection of furosemide and oral hydration. PET/CT findings were confirmed by MRI, cystoscopy, or biopsy. RESULTS: PET/CT was able to detect bladder lesions in 6 of 11 patients who had not undergone cystectomy. These images changed the PET/CT final reading in 7 patients: Recurrent bladder lesions were detected in 6 patients, pelvic lymph node metastases in 2 patients, and prostate metastasis in 1. This technique overcame the difficulties posed by the urinary excretion of (18)F-FDG. Hypermetabolic lesions could be easily detected by PET and precisely localized in the bladder wall, pelvic lymph nodes, or prostate by CT. Seven of 17 patients (41%) were upstaged only after delayed pelvic images. CONCLUSION: Detection of locally recurrent or residual bladder tumors can be dramatically improved using (18)F-FDG PET/CT with delayed images after a diuretic and oral hydration.

Normal values of [99mTc]pertechnetate uptake and excretion fraction by major salivary glands.

The assessment of the functional status of the salivary glands has been used in the scintigraphic evaluation of xerostomia. Several quantitative methods derived from standard dynamic scintigraphy have been suggested. However, the indices proposed are quite variable and unlikely to be useful in clinical practice. The objectives of this study were to obtain reference values of major salivary glands uptake and excretion fraction in healthy subjects and to obtain normal ratios of Tc-pertechnetate uptake by the major salivary glands in comparison to the thyroid gland uptake. The standardization of these values has the purpose of making this evaluation faster and more objective. Fifty volunteers without clinical evidence of xerostomia or thyroid disease underwent static salivary glands scintigraphy with Tc-pertechnetate. Static images were obtained at 20 minutes and then at 3 minutes after oral stimulation with lemon juice. Percent uptake, excretion fraction and salivary gland to thyroid ratio rates were calculated for the parotid and the submandibular glands. The mean of the uptake values at 20 minutes for the right and left parotid glands were respectively 0.31% and 0.26%, and for the submandibular glands 0.15%. The excretion fraction of the tracer after the lemon juice stimulation was 70% for the parotids glands, 50% for the right and 49% for the left submandibular glands. The mean+/-SD salivary gland to thyroid count ratio was 0.79+/-0.45 for the right parotid, 0.78+/-0.5 for the left parotid, 0.67+/-0.33 and 0.66+/-0.34 for the right and left submandibular glands, respectively. Salivary glands scintigraphy with uptake and excretion fraction calculation is an easy to perform, non-invasive and objective method to investigate salivary glands function. These findings help the nuclear physician to interpret salivary gland scintigraphy more objectively, even in patients with thyroid gland dysfunction in whom Tc-pertechnetate thyroid uptake may be abnormal.

51Cr-EDTA measurements of the glomerular filtration rate in patients with sickle cell anaemia and minor renal damage.

BACKGROUND: Creatinine clearance has been reported to be inaccurate for the estimation of glomerular filtration rate (GFR) in patients with sickle cell anaemia (SCA). Inulin clearance, the reference method for GFR estimation, is impractical for routine use in these patients, and 51Cr-EDTA measurements of the GFR have been rarely reported in this disease. METHODS: In order to obtain reference 51Cr-EDTA values in this disease, we studied 70 patients (40 females; 13-59 years of age, mean: 31.6 years) with homozygous SCA, normal serum creatinine and urinary albumin excretion < or =200 microg x min(-1). All patients were submitted to single-injection 51Cr-EDTA GFR, urinary albumin and haematocrit measurements. 51Cr-EDTA clearances were calculated in different age groups (<20, 20-29, 30-39, 40-49 and >50 years). RESULTS: The mean GFR (+/-standard deviation) obtained for the 70 patients was 111.5+/-23.1 ml x min(-1). Analysis of variance for evaluation of the possible interaction effect between 51Cr-EDTA clearance and sex, age, urinary albumin and haematocrit demonstrated patient age as the only factor influencing 51Cr-EDTA clearance (P < 0.001). The Spearman correlation coefficient showed a significant relationship between 51Cr-EDTA clearance and patient age (r = -0.44, P = 0.0001), but not between 51Cr-EDTA and urinary albumin (r = -0.17, P = 0.1546) or haematocrit (r = 0.079, P = 0.5121). The group aged 20-29 years presented the highest 51Cr-EDTA clearance mean value (126.7+/-20.4 ml x min(-1)), with a progressive reduction in the older groups. CONCLUSION: Young adults with homozygous SCA, normal serum creatinine and micro-albuminuria or normo-albuminuria present supranormal 51Cr-EDTA GFR values. These values rapidly decrease after 30 years of age. We did not find association between urinary albumin and GFR in these patients.

Skeletal Tumor Burden on Baseline 18F-Fluoride PET/CT Predicts Bone Marrow Failure After 223Ra Therapy.

PURPOSE: Determine if skeletal tumor burden on 18F-fluoride PET/CT (fluoride PET/CT) predicts the risk of bone marrow failure (BMF) after 223Ra dichloride therapy (223Ra). METHODS: Forty-one metastatic prostate cancer patients (43-89 years old; mean, 71 ± 9 years.) underwent fluoride PET/CT prior to 223Ra. Bone marrow failure was the primary end point and was defined as (1) development of hematologic toxicity (World Health Organization grade 3 or 4) associated with no recovery after 6 weeks or (2) death due to BMF after the last 223Ra dose. Bone marrow failure was correlated to fluoride PET/CT skeletal tumor burden (TLF10 [total lesion on fluoride PET/CT with SUVmax of 10 or greater]), use of chemotherapy, serum hemoglobin concentration, serum ALP, and serum prostate-specific antigen. RESULTS: The number of 223Ra cycles ranged from 2 to 6 (mean, 5). Of the 41 patients, 16 developed BMF (G3 = 12; G4 = 4). A significantly increased risk of developing BMF was observed in patients with TLF10 of 12,000 or greater (hazard ratio [HR], 11.09; P < 0.0001), hemoglobin of less than 10 g/dL (HR, 7.35; P = 0.0002), and AP > 146 UI/L (HR, 4.52; P = 0.0100). Neither concomitant (HR, 0.91; P = 0.88) nor subsequent use of chemotherapy (HR, 0.14; P = 0.84) increased the risk of BMF, nor was prostate-specific antigen greater than 10 µg/L (HR, 0.90; P = 0.86). Moreover, in a multivariable analysis, TLF10 was the only independent predictor of BMF (HR, 6.66; P = 0.0237). CONCLUSIONS: 223Ra was beneficial and reduced the risk of death even in patients with a high skeletal tumor burden. Fluoride PET/CT is able to determine which patients will benefit from 223Ra and which will develop BMF.

The Role of SPECT/CT Lymphoscintigraphy and Radioguided Sentinel Lymph Node Biopsy in Managing Papillary Thyroid Cancer.

IMPORTANCE: Single-photon emission computed tomography/computed tomography (SPECT/CT) and radioguided sentinel lymph node biopsy (rSLNB) are techniques that could potentially benefit surgeons and pathologists in the identification of sentinel lymph node (SLN) metastases in patients with papillary thyroid carcinoma (PTC). Evidence suggests that these novel techniques lead to substantial changes in PTC management by reducing understaging and of occult lymph node (LN) metastases and optimizing neck surgery by increasing the necessity of lateral lymphadenectomy and decreasing central lymphadenectomy. OBJECTIVES: To correlate the presence of LN metastases in PTC with clinical and pathological features using SPECT/CT and rSLNB. DESIGN, SETTING, AND PARTICIPANTS: For this prospective cohort study from June 2010 to November 2013, 42 patients with thyroid nodules suspicious for papillary carcinoma or classified as malignant on cytology examination without suspicion of lymph node metastases by clinical and ultrasound examinations were recruited from a single public medical institution. INTERVENTIONS: All 42 patients underwent preoperative lymphoscintigraphy after an ultrasound-guided peritumoral injection of Technetium Tc 99m nanocolloid. Cervical images were acquired with a SPECT/CT scanner 15 minutes after radiotracer injection. Approximately 2 hours after lymphoscintigraphy, the patients were submitted to intraoperative rSLNB using a handheld gamma probe. All SLNs identified were removed alongside with non-SLNs from the same compartment. Papillary thyroid carcinoma, SLNs and non-SLNs were submitted for histopathology and immunohistochemical analyses. RESULTS: Of the 42 patients initially enrolled, 37 were included in analysis, including 6 men and 31 women with a mean (range) age of 47 (22-83) years. Overall, T stage was as follows: T1, 23 patients (62.2%); T2, 8 patients (21.6%); and T3, 6 patients (16.2%). Sentinel lymph nodes were identified in 92% of the patients, and among these metastases were present in 17 patients (46%). The SLNs were false-negative in 3 patients. Metastases in the lateral compartment ocurred in 7 patients (18%). There was a significant association between LN metastases and tumor size (odds ratio, 1.06; 95% CI, 1.00-1.13; P = .02), with a Cohen d effect of 0.683 (medium to large effect). Overall, 17 patients (46%) with LN metastases had management changed because they were submitted to higher radioiodine ablation doses and closer clinical surveillance. CONCLUSIONS AND RELEVANCE: Radioguided SLNB is able to detect occult cervical lymph node metastases in patients with papillary thyroid carcinoma, and in 7 patients (18%) rSLNB detected lymph node metastases in the lateral compartments. The rSLNB technique lead to management change in 14 patients (37.8%).

High pre-therapy [99mTc]pertechnetate thyroid uptake, thyroid size and thyrostatic drugs: predictive factors of failure in [131I]iodide therapy in Graves' disease.

BACKGROUND AND OBJECTIVE: Several factors may interfere with the success rate of radioiodine therapy (RIT) in Graves' disease. Our aim was to evaluate, retrospectively, some of these factors in the outcome of RIT. METHODS: Patient gender, age at diagnosis, ophthalmopathy, disease duration, thyroid size, drug used as clinical treatment, thionamide withdrawal period during RIT preparation, FT4, TSH and [99mTc]pertechnetate thyroid uptake prior to RIT were studied as potential interference factors for RIT success. Eighty-two Graves' disease patients were submitted to RIT after thionamide treatment failure. Prior to RIT, 67 patients were receiving methimazole and 15 propylthiouracil. Thirty-three patients received thionamides during RIT; in 49 patients the medication was withdrawn for 2-30 days. [99mTc]pertechnetate thyroid uptake was determined before RIT. Fixed doses of 370 MBq of [131I]iodide were administered to all patients. RESULTS: Eleven patients became euthyroid; 40 became hypothyroid and 31 remained hyperthyroid. There was no association between outcome and age at diagnosis, gender, ophthalmopathy, pre-RIT FT4, TSH, antithyroid antibodies or thyrostatic drug. Multiple logistic regression showed higher probability of treatment success in patients with thyroid mass <53 g (odds ratio (OR)=8.9), with pre-RIT thyroid uptake <12.5% (OR=4.1) and in patients who withdrew thionamide before RIT (OR=4.9). CONCLUSIONS: Fixed doses of 370 MBq of radioiodine seem to be practical and effective for treating Graves' disease patients with [99mTc]pertechnetate uptake <12.5% and thyroid mass <53 g. This treatment is clearly not recommended for patients with large goitre. In contrast to what could be expected, patients with a high pre-RIT thyroid uptake presented a higher rate of RIT failure.

Determination of Skeletal Tumor Burden on 18F-Fluoride PET/CT.

UNLABELLED: The purpose of this study was to define a method to assess skeletal tumor burden with 18F-labeled sodium fluoride PET/CT (18F-fluoride PET/CT) and evaluate the reproducibility of these measurements. METHODS: Ninety-eight consecutive patients (90 men; mean age±SD, 65.7±14.2 y) underwent 158 18F-fluoride PET/CT scans for evaluation of skeletal metastatic disease. In order to determine the mean normal bone SUV, initially a 1-cm spheric volume of interest (VOI) was placed over 5 bone sites: T12, L5, sacrum, right iliac bone, and right femur. For each patient, the mean SUVmax for all sites was generated. Afterward, a threshold value of normal bone uptake was established. Subsequently, skeletal tumor burden was determined by generating volumetric data using a whole-body segmentation method. Any SUVmax below the normal threshold was excluded from analysis, as were VOIs not related to metastatic disease. Statistics for the remaining VOIs were then generated and defined as the skeletal metastatic tumor burden by 2 parameters: total lesion fluoride uptake above an SUVmax of 10 (TLF10) and fluoride tumor volume above an SUVmax of 10 (FTV10). TLF10 and FTV10 reproducibility was determined using 2 independent and experienced PET/CT interpreters analyzing a subset of 13 18F-fluoride PET/CT scans. RESULTS: Mean (±SD) normal bone SUVmax was 6.62±1.55 for T12, 6.11±1.73 for L5, 4.59±1.74 for sacrum, 5.39±1.72 for right iliac bone, and 3.90±1.57 for right femur. The mean normal SUVmax for all 543 sites was 5.32±0.99. On the basis of these values, an SUVmax threshold of 10 was chosen to exclude normal bone from the volumetric calculations. Semiautomated measurements of TLF10 and FTV10 exhibited high interobserver reproducibility, within ±0.77% and ±3.62% of the interinterpreter average for TLF10 and FTV10, respectively. CONCLUSION: Determination of skeletal tumor burden with 18F-fluoride PET/CT is feasible and highly reproducible. Using an SUVmax threshold of 10 excludes nearly all normal bone activity from volumetric calculations.

Prognostic Factors in Patients Treated with 223Ra: The Role of Skeletal Tumor Burden on Baseline 18F-Fluoride PET/CT in Predicting Overall Survival.

UNLABELLED: The purpose of this study was to evaluate outcome after (223)Ra dichloride therapy ((223)Ra) and to determine whether skeletal tumor burden on whole-body (18)F-fluoride PET/CT can be used as a predictive biomarker of survival in patients treated with (223)Ra. METHODS: Forty-two patients with hormone-refractory prostate cancer underwent (223)Ra and a baseline fluoride PET/CT scan. Fluoride PET/CT parameters were generated, including maximum standardized uptake value (SUVmax) of the hottest lesion (hSUVmax), average SUV of disease (Mean10), and skeletal tumor burden indices of total fluoride skeletal metastatic lesion uptake (TLF10) and total volume of fluoride avid bone metastases (FTV10). Overall survival (OS) was the primary endpoint. Secondary endpoints were progression-free survival and skeletal-related event (SRE). RESULTS: Skeletal tumor burden indices (TLF10 and FTV10) derived from fluoride PET/CT at baseline were highly correlated and significant independent predictors of OS (P = 0.0212; hazard ratio = 5.990; 95% confidence interval = 1.306-27.475). A TLF10 cutoff value of 8,000 discriminated survivors from nonsurvivors after (223)Ra (with TLF10 values < 8,000, the median OS was not estimated, whereas with TLF10 > 8,000, the median OS was 6.67 mo). Visual analysis, Mean10, and hSUVmax were not predictors of OS or progression-free survival. Mean10 was found to be a significant univariate predictor of the odds of having an SRE (P = 0.0445; odds ratio = 1.30; 95% confidence interval = 1.006-1.681), with a Mean10 greater than 19 increasing the risk of SRE. CONCLUSION: Skeletal tumor burden on baseline fluoride PET/CT is a predictive biomarker of OS and the risk of an SRE in patients treated with (223)Ra.

Polymorphism in LEP and LEPR May Modify Leptin Levels and Represent Risk Factors for Thyroid Cancer.

Purpose. To understand the role of polymorphisms in the LEP (rs7799039 and rs2167270) and LEPR (rs1137101 and rs1137100) genes in DTC susceptibility and their effect on leptin levels. Methods. We studied 153 patients with DTC and 234 controls through TaqMan SNP Genotyping and ELISA, comparing these data to the clinicopathological data of patients with DTC. Results. Patients with AA genotype of rs7799039 had higher levels of serum leptin (9.22 ± 0.98 ng/mL) than those with AG genotype (10.07 ± 0.60 ng/mL; P = 0.005). Individuals with AG genotype of rs2167270 also produced higher serum leptin levels (10.05 ± 0.59 ng/mL) than the subjects with GG genotype (9.52 ± 0.79 ng/mL; P < 0.05). A multivariate logistic regression adjusted for gender, age, and BMI showed that the AG genotype of rs7799039 was an independent risk for DTC (OR, 11.689; P = 0.0183; 95% CI, 1.516-90.119). Similarly, AG and GG genotypes of rs1137101 increased the susceptibility to DTC (OR, 3.747; P = 0.027; 95% CI, 1.161-12.092 and OR, 5.437; P = 0.013; 95% CI, 1.426-20.729). Conclusions. We demonstrated that rs7799039 and rs2167270 polymorphisms modify the serum leptin concentrations in patients with DTC. Furthermore, polymorphisms rs7799039 and rs1137101 increase the risk of DTC development, although they do not correlate with tumor aggressiveness.

Elevated thalamic and prefrontal regional cerebral blood flow in obsessive-compulsive disorder: a SPECT study.

Functional neuroimaging studies have pointed to a possible role of cerebral circuits involving the prefrontal and anterior cingulate cortices, the striatum, and thalamus in the pathophysiology of obsessive-compulsive disorder (OCD). Regional cerebral blood flow (rCBF) of 16 drug-free Brazilian patients with OCD and 17 healthy subjects matched for age, gender, handedness and level of education was measured with [99m-Tc] HMPAO single photon emission computed tomography. Analysis of covariance identified four regions of interest with significantly higher rCBF: the right superior and inferior frontal cortex and the right and left thalamus. Positive correlations between symptom severity measured by Clinical Global Impression scores and rCBF were found in the right and left inferior frontal lobes and in the right basal ganglia. Compulsive behavior was inversely correlated with rCBF in the right thalamus, and duration of illness correlated positively with rCBF in the right and left superior frontal lobes and with the right thalamus. The findings of this SPECT study conducted in Brazil are in agreement with prior studies and provide additional support for the involvement of prefrontal-subcortical circuits in the pathophysiology of OCD. Furthermore, the study suggests that similar brain mechanisms appear to be involved cross-culturally.

Lateralization of epileptiform discharges in patients with epilepsy and precocious destructive brain insults.

Unilateral destructive brain lesions of early development can result in compensatory thickening of the ipsilateral cranial vault. The aim of this study was to determine the frequency of these bone changes among patients with epilepsy and precocious destructive lesions, and whether a relationship exists between these changes and epileptiform discharges lateralization. Fifty-one patients had their ictal / interictal scalp EEG and skull thickness symmetry on MRI analyzed. Patients were divided into three main groups according to the topographic distribution of the lesion on the MRI: hemispheric (H) (n=9); main arterial territory (AT) (n=25); arterial borderzone (Bdz) (n=17). The EEG background activity was abnormal in 26 patients and were more frequent among patients of group H (p= 0.044). Thickening of the skull was more frequent among patients of group H (p= 0.004). Five patients (9.8%) showed discordant lateralization between epileptiform discharges and structural lesion (four of them with an abnormal background, and only two of them with skull changes). In one of these patients, ictal SPECT provided strong evidence for scalp EEG false lateralization. The findings suggest that compensatory skull thickening in patients with precocious destructive brain insults are more frequent among patients with unilateral and large lesions. However, EEG lateralization discordance among these patients seems to be more related to EEG background abnormalities and extent of cerebral damage than to skull changes.

Evaluation of soft-tissue lesions with (18)F-FDG PET/CT: initial results of a prospective trial.

PURPOSE OF THE REPORT: Although MRI is utilized for planning the resection of soft-tissue tumors, it is not always capable of differentiating benign from malignant lesions. The risk of local recurrence of soft-tissue sarcomas is increased when biopsies are performed before resection and by inadequate resections. PET associated with computed tomography using fluorodeoxyglucose labeled with fluorine-18 ((18)F-FDG PET/CT) may help differentiate between benign and malignant tumors, thus avoiding inadequate resections and making prior biopsies unnecessary. The purpose of this study was to evaluate the usefulness of (18)F-FDG PET/CT in differentiating benign from malignant solid soft-tissue lesions. MATERIALS AND METHODS: Patients with solid lesions of the limbs or abdominal wall detected by MRI were submitted to (18)F-FDG PET/CT. The maximum standardized uptake value (SUVmax) cutoff was determined to differentiate malignant from benign tumors. Regardless of the (18)F-FDG PET/CT results all patients underwent biopsy and surgery. RESULTS: MRI was performed in 54 patients, and 10 patients were excluded because of purely lipomatose or cystic lesions. (18)F-FDG PET/CT was performed in the remaining 44 patients. Histopathology revealed 26 (59%) benign and 18 (41%) malignant soft-tissue lesions. A significant difference in SUVmax was observed between benign and malignant soft-tissue lesions. The SUVmax cutoff of 3.0 differentiated malignant from benign lesions with 100% sensitivity, 83.3% specificity, 89.6% accuracy, 78.3% positive predictive value, and 100% negative predictive value. CONCLUSION: (18)F-FDG PET/CT seems to be able to differentiate benign from malignant soft-tissue lesions with good accuracy and very high negative predictive value. Incorporating (18)F-FDG PET/CT into the diagnostic algorithm of these patients may prevent inadequate resections and unnecessary biopsies.

Is thyroid stunning clinically relevant? A retrospective analysis of 208 patients.

OBJECTIVE: Current guidelines have advised against the performance of (131)I-iodide diagnostic whole body scintigraphy (dxWBS) to minimize the occurrence of stunning, and to guarantee the efficiency of radioiodine therapy (RIT). The aim of the study was to evaluate the impact of stunning on the efficacy of RIT and disease outcome. SUBJECTS AND METHODS: This retrospective analysis included 208 patients with differentiated thyroid cancer managed according to a same protocol and followed up for 12-159 months (mean 30 ± 69 months). Patients received RIT in doses ranging from 3,700 to 11,100 MBq (100 mCi to 300 mCi). Post-RIT-whole body scintigraphy images were performed 10 days after RIT in all patients. In addition, images were also performed 24-48 hours after therapy in 22 patients. Outcome was classified as no evidence of disease (NED), stable disease (SD) and progressive disease (PD). RESULTS: Thyroid stunning occurred in 40 patients (19.2%), including 26 patients with NED and 14 patients with SD. A multivariate analysis showed no association between disease outcome and the occurrence of stunning (p = 0.3476). CONCLUSION: The efficacy of RIT and disease outcome do not seem to be related to thyroid stunning.