The Role of Nuclear Medicine in Benign Thyroid Disease.

Since the mid-twentieth century, the radionuclide thyroid scan has been utilized in the management of benign thyroid disorders. In current medical practice, patients with hyperthyroidism are referred for thyroid scintigraphy, while patients with goiters and thyroid nodules are most often evaluated by ultrasound or computed tomography. Since thyroid scintigraphy reflects the functional state of the gland, it provides information that anatomical imaging lacks. Therefore, radionuclide imaging of the thyroid is the imaging modality of choice in the evaluation of the hyperthyroid patient. In addition, patients with so-called subclinical hyperthyroidism often present a diagnostic dilemma to the clinician since the causative factor must be determined for proper patient management. The aim of this manuscript is to illustrate the imaging characteristics of thyroid disorders commonly seen in clinical practice resulting in thyrotoxicosis or pending thyrotoxicosis, so that correlation with clinical presentation and pertinent laboratory data will lead to the correct diagnosis.

18F-FDG PET/CT Staging of Head and Neck Cancer: Interobserver Agreement and Accuracy-Results from Multicenter ACRIN 6685 Clinical Trial.

To our knowledge, no prior multicenter clinical trial has reported interobserver agreement of 18F-FDG PET/CT scans for staging of clinical N0 neck in head and neck cancer. Methods: A total of 287 participants were recruited. For visual analysis, positive nodal uptake of 18F-FDG was defined as uptake visually greater than activity seen in the blood pool. Results: The negative predictive value of the 18F-FDG PET/CT for N0 clinical neck was 86% or above for visual assessment (95% CI, 86%-88%) for the 2 central readers and above 90% (95% CI, 90%-95%) for SUVmax for central reads and site reads dichotomized at the optimal cutoff value of 1.8 and the prespecified cutoff value of 3.5, respectively. The κ coefficients between the 2 expert readers and between central reads and site reads varied between 0.53 and 0.78. Conclusion: The NPV of the 18F-FDG PET/CT for N0 clinical neck was 86% or above for visual assessment and above 90% for SUVmax cut points of 1.8 and 3.5 with moderate to substantial agreements.

How much time is enough? Sentinel lymph node mapping time depends on the radiotracer agent.

BACKGROUND: In 2014, technetium-99m tilmanocept (TcTM) replaced technetium-99m sulfur colloid (TcSC) as the standard lymphoscintigraphy (LS) mapping agent in melanoma patients undergoing sentinel lymph node biopsy (SLNB). The aim of this study was to examine differences in mapping time, intra-operative identification of sentinel lymph node (SLN), and false negative rate (FNR) between patients who underwent SLNB with TcTM compared to TcSC. METHODS: Patients who underwent SLNB between 2010 and 2018 were retrospectively identified. Patient demographic, tumor, and imaging data was stratified by receipt of TcSC (n = 258) or TcTM (n = 133). Student's t test and χ2 test were used to compare characteristics and outcomes. RESULTS: Both cohorts were similar in demographic, primary tumor characteristics, and total number of SLN identified (TcTM 3.56 vs. TcSC 3.28, p = 0.244). TcTM was associated with significantly shorter LS mapping times (51.8 vs. 195.1 min, p < 0.01). There was no significant difference in the number of patients with positive SLN (TcTM 11.3 vs. TcSC 17.4%, p = 0.109) and the FNR was similar between both groups (TcTM 25% vs. TcSC 22%). CONCLUSION: TcTM was associated with significantly shorter LS mapping time while identifying similar numbers of SLN. Our results support further study to ensure similar FNR and oncologic outcomes between agents.

Imaging urothelial bladder cancer: A VPAC PET targeted approach.

INTRODUCTION Accurate staging of urothelial bladder cancer (UBC) with imaging, which guides effective bladder cancer treatment, remains challenging. This investigation is to validate a hypothesis that targeting Vasoactive intestinal and pituitary adenylate cyclase activating peptide (VPAC) receptors using 64Cu-TP3805 can PET image UBC efficiently. MATERIALS AND METHODS: Nineteen patients (44-84 years of age) scheduled for radical cystectomy, underwent VPAC positron emission tomography (PET) imaging prior to surgery. Sixteen had completed neoadjuvant chemotherapy prior to imaging. All 19 received 64Cu-TP3805 (148 % ± 10% MBq) intravenously, and were imaged 60 to 90 minutes later. Standard uptake value (SUV)max for malignant lesions and SUVmean for normal tissues were determined and mean +/-SEM recorded. Following radical cystoprostatectomy, pelvic lymphadenectomy and urinary diversion imaging, results were compared with final surgical pathology. RESULTS: 64Cu-TP3805 had no adverse events, negligible urinary excretion and rapid blood clearance. UBC PET images for residual disease were true positive in 11 patients and true negative in four. Of remaining 4, one had false positive and 3 had false negative scans, equating to 79% sensitivity (95%, CI 49%-95%), 80% specificity (95%, CI 28%-100%), 92% positive predictive value (95%, CI 62%-100%) and 57% negative predictive value (95%, CI 18%-90%). CONCLUSIONS: These first in man results, in a group, heavily pretreated with neoadjuvant chemotherapy, indicate that VPAC PET imaging can identify UBC effeiciently and suggest, that VPAC PET can diagnose UBC in a treatment naïve cohort for accurate staging, guide biopsy and treatment in patients with suspected metastasis and determine response to therapy. Further investigation of this molecular imaging approach is warranted.

US-triggered Microbubble Destruction for Augmenting Hepatocellular Carcinoma Response to Transarterial Radioembolization: A Randomized Pilot Clinical Trial.

Background US contrast agents are gas-filled microbubbles (MBs) that can be locally destroyed by using external US. Among other bioeffects, US-triggered MB destruction, also known as UTMD, has been shown to sensitize solid tumors to radiation in preclinical models through localized insult to the vascular endothelial cells. Purpose To evaluate the safety and preliminary efficacy of combining US-triggered MB destruction and transarterial radioembolization (TARE) in participants with hepatocellular carcinoma (HCC). Materials and Methods In this pilot clinical trial, participants with HCC scheduled for sublobar TARE were randomized to undergo either TARE or TARE with US-triggered MB destruction 1-4 hours and approximately 1 and 2 weeks after TARE. Enrollment took place between July 2017 and February 2020. Safety of US-triggered MB destruction was evaluated by physiologic monitoring, changes in liver function tests, adverse events, and radiopharmaceutical distribution. Treatment efficacy was evaluated by using modified Response Evaluation Criteria in Solid Tumors (mRECIST) on cross-sectional images, time to required next treatment, transplant rates, and overall survival. Differences across mRECIST reads were compared by using a Mann-Whitney U test, and the difference in prevalence of tumor response was evaluated by Fisher exact test, whereas differences in time to required next treatment and overall survival curves were compared by using a log-rank (Mantel-Cox) test. Results Safety results from 28 participants (mean age, 70 years ± 10 [standard deviation]; 17 men) demonstrated no significant changes in temperature (P = .31), heart rate (P = .92), diastolic pressure (P = .31), or systolic pressure (P = .06) before and after US-triggered MB destruction. No changes in liver function tests between treatment arms were observed 1 month after TARE (P > .15). Preliminary efficacy results showed a greater prevalence of tumor response (14 of 15 [93%; 95% CI: 68, 100] vs five of 10 [50%; 95% CI: 19, 81]; P = .02) in participants who underwent both US-triggered MB destruction and TARE (P = .02). Conclusion The combination of US-triggered microbubble destruction and transarterial radioembolization is feasible with an excellent safety profile in this patient population and appears to result in improved hepatocellular carcinoma treatment response. © RSNA, 2020.

The impact of risk factors on gastroparesis at an urban medical center.

BACKGROUND: Gastroparesis is a complex and poorly understood disease. The literature is lacking with respect to the epidemiology of patient comorbidities and their effect on gastric emptying. We aimed to describe the most common comorbid conditions among patients with gastroparesis in an urban population and quantify the effect of these comorbidities on the severity of delayed gastric emptying (DGE). METHODS: We examined the medical records of all patients diagnosed with gastroparesis at a quaternary care center between 2014 and 2015. The severity of DGE was analyzed after patients were stratified for possible causative etiologies. Likelihood ratio tests were used to assess the significance of demographic and scintigraphic variation in this population. RESULTS: Of the 221 patients, 56.1% were Caucasian and 31.7% were African American. Among these patients, 29.4% had evidence of medication-associated gastroparesis, 29.0% had diabetes-associated gastroparesis, and 31.7% had idiopathic disease. African American patients with gastroparesis were more likely to have diabetic gastroparesis than patients of other races (P=0.01). There was a statistically significant relationship between the number of major risk factors and the severity of a patient's DGE (P=0.004). CONCLUSIONS: Among a diverse urban population, patients with DGE often carry multiple comorbid conditions that serve as risk factors for the development of gastroparesis, including prescriptions for narcotic medications. Greater numbers of these comorbid conditions are associated with more severe disease. Demographics are significantly associated with the etiology and severity of gastroparesis; in particular, African American patients are more likely to have diabetic gastroparesis than patients of other races.

N-Acetyl Cysteine Is Associated With Dopaminergic Improvement in Parkinson's Disease.

This study assessed the biological and clinical effects in patients with Parkinson's disease (PD) of N-acetyl-cysteine (NAC), the prodrug to l-cysteine, a precursor to the natural biological antioxidant glutathione. Forty-two patients with PD were randomized to either weekly intravenous infusions of NAC (50 mg/kg) plus oral doses (500 mg twice per day) for 3 months or standard of care only. Participants received prebrain and postbrain imaging with ioflupane (DaTscan) to measure dopamine transporter (DAT) binding. In the NAC group, significantly increased DAT binding was found in the caudate and putamen (mean increase from 3.4% to 8.3%) compared with controls (P < 0.05), along with significantly improved PD symptoms (P < 0.0001). The results suggest NAC may positively affect the dopaminergic system in patients with PD, with corresponding positive clinical effects. Larger scale studies are warranted.

Disparity in the use of adjuvant radioactive iodine ablation among high-risk papillary thyroid cancer patients.

BACKGROUND: We sought to identify treatment disparities existing prior to publication of the 2015 American Thyroid Association Management Guidelines in order to identify patients with papillary thyroid cancer (PTC) at risk for receiving inadequate treatment. METHODS: Patients diagnosed with PTC from 2011 to 2013 were identified using Surveillance, Epidemiology and End Results database. High-risk disease was defined as T4, N1, or M1. Chi-square tests compared characteristics of patients with and without high-risk disease and characteristics of high-risk patients who did and did not receive radioactive iodine ablation (RAI). Likelihoods of having high-risk disease, of receiving RAI, and of cause-specific death were calculated using regression analyses. RESULTS: Sample included 32,229 individuals; 7894 (24.5%) had high-risk disease. Mean age was 50.0 years, 24,815 (77.0%) were female, and 21,318 (66.2%) were white. Odds of high-risk disease were greater among males (OR:2.04; 95% CI:1.92-2.16), Hispanics (OR:1.67; 95% CI:1.56-1.79) and Asians (OR:1.49; 95% CI:1.37-1.62), and uninsured (OR:1.24; 95% CI:1.07-1.43), and lower among patients ages 45-64 (OR:0.57; 95% CI:0.53-0.60), and ≥65 years (OR:0.54; 95% CI:0.50-0.59), and Blacks (OR:0.46; 95% CI:0.40-0.53). Most (69.3%) high-risk patients received RAI. Odds of receiving RAI were lower among patients age ≥65 years (OR:0.67; 95% CI:0.58-0.77), uninsured (OR:0.52; 95% CI:0.41-0.67), or with Medicaid (OR:0.58; 95% CI:0.50-0.69). RAI use reduced the risk of cause-specific mortality (HR:0.29; 95% CI:0.18-0.47). CONCLUSION: Knowledge of these treatment disparities will allow recognition of groups at risk for high-risk disease and receiving inadequate treatment.

Recent Trends Suggest Possible Inappropriate Utilization of Myocardial Perfusion Imaging.

PURPOSE: The aim of this study was to analyze the utilization of elective stress nuclear myocardial perfusion imaging (MPI) in the Medicare population. METHODS: Nationwide Medicare Part B fee-for-service databases for 2004 to 2016 were reviewed. Current Procedural Terminology codes for stress MPI were selected: standard planar and single-photon emission computed tomography (STD) and PET. Utilization rates per 1,000 Medicare beneficiaries were calculated. Elective examinations were identified using place-of-service codes for private offices and hospital outpatient departments (HOPDs). Medicare physician specialty codes identified the performing physician. Because Medicare Part B databases are complete population counts, sample statistics were not required. RESULTS: Elective STD MPI utilization peaked in 2006 at 74 studies/1,000 and had declined by 36% by 2016. Cardiologists' share of STD MPI grew from 79% to 87% between 2004 and 2016. Cardiologists perform STD MPI primarily in private offices, where utilization peaked in 2008 and then demonstrated an absolute decline of 28 studies/1,000 by 2016. During this same time period, cardiologists' use of STD MPI in HOPDs demonstrated an absolute increase of 8.1 studies/1,000. From 2004 to 2016, STD MPI use by radiologists declined by 58%. Elective PET MPI maintained an upward trend, reflecting increasing use by cardiologists in private offices. CONCLUSIONS: Elective STD MPI use is declining, but cardiologists are performing an increasing share in outpatient settings. The drop in private office STD MPI among cardiologists was far greater than the corresponding increase in its use in HOPDs, suggesting that many studies previously performed in private offices were unindicated. Self-referred PET MPI utilization has rapidly grown in cardiology private offices.

Does the dose of iodine-131 influence the incidence of Graves' ophthalmopathy?

BACKGROUND: Radioactive iodine-131 (RAI) is an established treatment for patients with Graves' hyperthyroidism. RAI is reported to be associated with a 20-30% incidence of development or exacerbation of Graves' ophthalmopathy (GO). This study compares the progression of GO in patients who had evidence or no evidence of GO before RAI therapy. PATIENTS AND METHODS: Forty-eight patients were studied. One group had no evidence whereas the other group had evidence of GO before RAI treatment. All underwent RAI therapy. Group A (27 patients, 18 women, nine men, age: 19-68 with a mean of 49 years) had pre-existing exophthalmos. Group B consisted of 21 patients (13 women, eight men, age: 30-63 with a mean of 43 years) developed exophthalmos after treatment. All patients underwent RAI therapy and followed by ophthalmologists. RESULTS: The average administered dose in group A was 24.3 mCi (range: 10-36.2 mCi) compared with group B: 25.4 mCi (range: 13-35.9 mCi), P=0.60. Ten (37%) of the 27 patients in group A experienced worsening of symptoms post-treatment. There was no significant difference between the administered dose of RAI in patients with worsening symptoms, 25.1 mCi versus patients with stable symptoms, 24.5 mCi (P=0.82). However, group A developed GO symptoms earlier than group B (4.5 vs. 9.5 months), P=0.02. CONCLUSION: RAI is known to exacerbate ophthalmopathy. Our study showed it was not dose-dependent. Patients without a previous history of GO were observed to have a significantly delayed period for the development of symptoms.

Consecutive Case Series of Melanoma Sentinel Node Biopsy for Lymphoseek Compared to Sulfur Colloids.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is an important adjunct in the staging of patients with melanoma. Preoperative lymphoscintigraphy with radiolabeled isotopes is essential to localize sentinel nodes for removal. Our study compared the effectiveness of Lymphoseek to standard sulfur colloids in patients with melanoma undergoing SLNB. METHODS: We queried our IRB-approved melanoma database to identify 370 consecutive patients who underwent SLNB from 2012 to 2016 with at least 1 y of follow-up. There were 185 patients in each group. Data points included characteristics of the primary melanoma lymphoscintigraphy and SLNB. Student's t-test and chi-square were used to analyze the data with a P value of <0.05 being considered significant. RESULTS: Patients were equally matched in regard to age, sex, and primary characteristics of their melanoma. In comparison to sulfur colloid, Lymphoseek required lower radiation dosages (P < 0.001), shorter mapping times (P = 0.008), and decreased number of sentinel nodes removed (P = 0.03). There was no difference in the number of patients with positive nodes (P = 0.5). In addition, there were no statistical differences between the two radioactive tracers in regard to the number of patients with false-negative SLNB. CONCLUSION: Lymphoseek has the potential to decrease radioactivity and mapping time in patients who need SLNB. With a decrease in the number of nodes removed without loss of sensitivity, there is a potential to avoid unnecessary node removal and thus complications such as lymphedema. Longer follow-up will help to determine if there is any increase in false-negative rates despite fewer nodes removed.

Nuclear Medicine and Resources for Patients: How Complex Are Online Patient Educational Materials?

The Internet is a major source of health care information for patients. The American Medical Association and the National Institutes of Health recommend that consumer health care websites be written at a third- to seventh-grade level. The purpose of this study was to evaluate the level of readability of patient education websites pertaining to nuclear medicine. Methods: We searched for 10 terms on Google, collected the top 10 links for each term, and analyzed their level of readability using 10 well-established readability scales. Results: Collectively, the 99 articles were written at a grade level of 11.8 (SD, 3.4). Only 5 of the 99 articles were written at the third- to seventh-grade level recommended by the National Institutes of Health and the American Medical Association. Conclusion: There is a clear discordance between the readability level of nuclear medicine-related imaging terms and the National Institutes of Health and American Medical Association guidelines. This discordance may have a negative impact on patient understanding, contributing to poor health outcomes.

VPAC1 Targeted 64Cu-TP3805 kit preparation and its evaluation.

INTRODUCTION: Previously, our laboratory has shown that 64Cu-TP3805 can specifically target VPAC1 receptors and be used for positron emission tomography (PET) imaging of breast (BC) and prostate cancer (PC) in humans. Present work is aimed at the formulation of a freeze-dried diaminedithiol-peptide (N2S2-TP3805) kit and it's evaluation for the preparation of 64Cu labeled TP3805. Parameters such as pH, temperature and incubation time were examined that influenced the radiolabeling efficiency and stability of the product. METHODS: Kits were prepared under different conditions and radiolabeling efficiency of TP3805 kit was evaluated for a range of pH3.5-8.5, after addition of 64Cu in 30µl, 0.1M HCl. Incubation temperature (37-90°C) and time (30-120min.) were also investigated. Kits were stored at -10°C and their long term stability was determined as a function of their radiolabeling efficiency. Further, stability of 64Cu-TP3805 complex was evaluated in presence of fetal bovine serum and bovine serum albumin by using SDS polyacrylamide gel electrophoresis. Kits were then used for PET imaging of BC and PC following eIND (101550) and institutional approvals. Specificity of 64Cu-TP3805 for VPAC1 was examined with digital autoradiography (DAR) of prostate tissues obtained after prostatectomy, benign prostatic hyperplasia (BPH) tissue, and benign and malignant lymph nodes. Results were compared with corresponding tissue histology. RESULTS: Radiolabeling efficiency was ≥95% at final pH ~7.2 when incubated at 50°C for 90min. Kits were stable up to 18months when stored at -10°C, and 64Cu-TP3805 complex exhibited excellent stability for up to 4h at room temperature. 64Cu-TP3805 complex did not show any transchelation even after 2h incubation at 37°C in 10% FBS as well as in BSA as determined by SDS PAGE analysis. DAR identified ≥95% of malignant lesions 11 new PC lesions, 20 high grade prostatic intraepithelial neoplasia, 2/2 ejaculatory ducts and 5/5 urethra verumontanum not previously identified The malignant lymph nodes were correctly identified by DAR and for 3/3 BPH patients, and 5/5 cysts, DAR was negative. In human BC (n=19) and PC (n=26) were imaged with 100% sensitivity. CONCLUSION: Availability of ready to use N2S2-peptide kits for 64Cu labeling is convenient and eliminates possible day to day variation during its routine preparation for clinical use.

N-Acetyl Cysteine May Support Dopamine Neurons in Parkinson's Disease: Preliminary Clinical and Cell Line Data.

BACKGOUND: The purpose of this study was to assess the biological and clinical effects of n-acetyl-cysteine (NAC) in Parkinson's disease (PD). METHODS: The overarching goal of this pilot study was to generate additional data about potentially protective properties of NAC in PD, using an in vitro and in vivo approach. In preparation for the clinical study we performed a cell tissue culture study with human embryonic stem cell (hESC)-derived midbrain dopamine (mDA) neurons that were treated with rotenone as a model for PD. The primary outcome in the cell tissue cultures was the number of cells that survived the insult with the neurotoxin rotenone. In the clinical study, patients continued their standard of care and were randomized to receive either daily NAC or were a waitlist control. Patients were evaluated before and after 3 months of receiving the NAC with DaTscan to measure dopamine transporter (DAT) binding and the Unified Parkinson's Disease Rating Scale (UPDRS) to measure clinical symptoms. RESULTS: The cell line study showed that NAC exposure resulted in significantly more mDA neurons surviving after exposure to rotenone compared to no NAC, consistent with the protective effects of NAC previously observed. The clinical study showed significantly increased DAT binding in the caudate and putamen (mean increase ranging from 4.4% to 7.8%; p<0.05 for all values) in the PD group treated with NAC, and no measurable changes in the control group. UPDRS scores were also significantly improved in the NAC group (mean improvement of 12.9%, p = 0.01). CONCLUSIONS: The results of this preliminary study demonstrate for the first time a potential direct effect of NAC on the dopamine system in PD patients, and this observation may be associated with positive clinical effects. A large-scale clinical trial to test the therapeutic efficacy of NAC in this population and to better elucidate the mechanism of action is warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT02445651.

Provider Distribution Changes in Dual-Energy X-Ray Absorptiometry in the Medicare Population Over the Past Decade.

Both radiologists as well as nonimaging physicians perform dual-energy X-ray absorptiometry (DXA) imaging in the United States. This study aims to compare provider distribution between these physician groups on the Medicare population, which is the predominant age group of patients evaluated by this imaging procedure. Using the 2 relevant Current Procedural Terminology, Fourth Edition codes for DXA scans, source data were obtained from the CMS Physician Supplier Procedure Summary Master Files from 2003 through 2013. DXA scan procedure volumes for radiologists and nonradiologists on Medicare patients were tabulated. Utilization rates were calculated. From 2003 to 2013, the total number of DXA scans performed on Medicare patients decreased by 2%. However, over the same period, the number of scans performed by radiologists had increased by 25% over nonimaging specialists, whose utilization had declined by approximately the same amount. From 2003 to 2013, the rate of utilization of DXA scans in the Medicare fee-for-service population declined somewhat. However, radiologists continue to gain market share from other specialists and now predominate in this type of imaging by a substantial margin.

Pancreatic Cancer in Lynch Syndrome: A Case Report.

Background: In the literature, pancreatic cancer is not frequently acknowledged among the tumors that are considered a part of Lynch Syndrome. Case Presentation: Our case is one of a young man who was found, very early in life, to have pancreatic cancer. His tumor demonstrated germline microsatellite instability, and hence by definition the patient has Lynch syndrome. He responded well to treatment, which included surgery and adjuvant chemotherapy. To date he remains in remission from pancreatic cancer. Conclusion: The rare instances in this case report include: (a) The patient had pancreatic cancer that fulfilled the histopathological and clinical criteria for Lynch syndrome. (b) Pancreatic cancer was diagnosed earlier in our patient than is expected in patients who suffer from pancreatic cancer as a part of Lynch syndrome. (c) Our patient had an excellent response to chemotherapy. He remains in remission to date from pancreatic cancer and is 5 years since his last treatment for this disease.

VPAC1 Targeted (64)Cu-TP3805 Positron Emission Tomography Imaging of Prostate Cancer: Preliminary Evaluation in Man.

OBJECTIVE: To evaluate (64)Cu-TP3805 as a novel biomolecule, to positron emission tomography (PET) image prostate cancer (PC), at the onset of which VPAC1, the superfamily of G protein-coupled receptors, is expressed in high density on PC cells, but not on normal cells. MATERIALS AND METHODS: Twenty-five patients undergoing radical prostatectomy were PET/X-ray computerized tomography imaged preoperatively with (64)Cu-TP3805. Standardized maximum uptake (SUVmax) values were determined and malignant lesions (standardized uptake value > 1.0) counted, and compared with histologic findings. Whole-mount pathology slides from 6 VPAC1 PET imaged patients, 3 benign prostatic hyperplasia patients, 1 malignant and 1 benign lymph node underwent digital autoradiography (DAR) after (64)Cu-TP3805 incubation and were compared to hematoxylin- and eosin-stained slides. RESULTS: In 25 patients who underwent PET imaging, 212 prostate gland lesions had SUVmax > 1.0 vs 127 lesions identified by histology of biopsy tissues. The status of the additional 85 PET identified prostate lesions remains to be determined. In 68 histologic slides from 6 PET imaged patients, DAR identified 105 of 107 PC foci, 19 of 19 high-grade prostatic intraepithelial neoplasias, and ejaculatory ducts and verumontanum involved with cancer. Additionally, DAR found 9 PC lesions not previously identified histologically. The positive and negative lymph nodes were correctly identified, and in 3 of 3 benign prostatic hyperplasia patients and 5 of 5 cysts, DAR was negative. CONCLUSION: This feasibility study demonstrated that (64)Cu-TP3805 delineates PC in vivo and ex vivo, provided normal images for benign masses, and is worthy of further studies.

Yttrium-90 Microsphere Brachytherapy for Liver Metastases From Uveal Melanoma: Clinical Outcomes and the Predictive Value of Fluorodeoxyglucose Positron Emission Tomography.

OBJECTIVES: To report outcomes after yttrium-90 microsphere brachytherapy for unresectable liver metastases from uveal melanoma and to evaluate factors predictive for overall survival (OS) and hepatic progression-free survival (PFS). METHODS: A total of 71 patients were consecutively treated with microsphere brachytherapy for unresectable liver metastases from uveal melanoma between 2007 and 2012. Clinical, radiographic, and positron emission tomography-derived, functional tumor parameters were evaluated by log-rank test in univariate analysis and backwards stepwise multivariate Cox proportional hazards regression. OS and hepatic PFS were estimated by Kaplan-Meier analysis. RESULTS: A total of 134 procedures were performed in 71 patients with a median age of 63 years (range, 23 to 91 y). Fifty-eight patients (82%) received microsphere brachytherapy as a salvage therapy. Median hepatic PFS and OS after microsphere brachytherapy were 5.9 months (range, 1.3 to 19.1 mo) and 12.3 months (range, 1.9 to 49.3 mo), respectively. Median OS times after diagnosis of liver metastases was 23.9 months (range, 6.2 to 69.0 mo). In univariate analysis, female sex, pretreatment metabolic tumor volume, and total glycolic activity (TGA) were significantly correlated with hepatic PFS and OS. In multivariate analysis, female sex and TGA retained significance as independent predictors of hepatic PFS and OS. A low pretreatment TGA (<225 g) was associated with a significantly longer median OS than was a TGA≥225 g (17.2 vs. 9.7 mo, P=0.01). CONCLUSIONS: Yttrium-90 microsphere brachytherapy provided favorable survival times in patients with unresectable liver metastases from uveal melanoma. Metabolic tumor volume and TGA are predictive functional tumor parameters, which may aid patient selection and risk stratification.

(90)Y-clivatuzumab tetraxetan with or without low-dose gemcitabine: A phase Ib study in patients with metastatic pancreatic cancer after two or more prior therapies.

BACKGROUND: For patients with metastatic pancreatic adenocarcinoma, there are no approved or established treatments beyond the 2nd line. A Phase Ib study of fractionated radioimmunotherapy was undertaken in this setting, administering (90)Y-clivatuzumab tetraxetan (yttrium-90-radiolabelled humanised antibody targeting pancreatic adenocarcinoma mucin) with or without low radiosensitising doses of gemcitabine. METHODS: Fifty-eight patients with three (2-7) median prior treatments were treated on Arm A (N=29, (90)Y-clivatuzumab tetraxetan, weekly 6.5 mCi/m(2)doses×3, plus gemcitabine, weekly 200 mg/m(2) doses×4 starting 1 week earlier) or Arm B (N=29, (90)Y-clivatuzumab tetraxetan alone, weekly 6.5 mCi/m(2)doses×3), repeating cycles after 4-week delays. Safety was the primary endpoint; efficacy was also evaluated. RESULTS: Cytopaenias (predominantly transient thrombocytopenia) were the only significant toxicities. Fifty-three patients (27 Arm A, 26 Arm B, 91% overall) completed ⩾1 full treatment cycles, with 23 (12 Arm A, 11 Arm B; 40%) receiving multiple cycles, including seven (6 Arm A, 1 Arm B; 12%) given 3-9 cycles. Two patients in Arm A had partial responses by RECIST criteria. Kaplan-Meier overall survival (OS) appeared improved in Arm A versus B (hazard ratio [HR] 0.55, 95% CI: 0.29-0.86; P=0.017, log-rank) and the median OS for Arm A versus Arm B increased to 7.9 versus 3.4 months with multiple cycles (HR 0.32, P=0.004), including three patients in Arm A surviving >1 year. CONCLUSIONS: Clinical studies of (90)Y-clivatuzumab tetraxetan combined with low-dose gemcitabine appear feasible in metastatic pancreatic cancer patients beyond 2nd line and a Phase III trial of this combination is now underway in this setting.