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.

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.

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.

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.

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.

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.

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.

(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.

Effectiveness of PET/CT in the preoperative evaluation of neck disease.

OBJECTIVES/HYPOTHESIS: To evaluate the utility of positron emission tomography (PET)/computed tomography (CT) for staging the neck in the preoperative setting by comparing it to both CT/magnetic resonance imaging (MRI) and pathologic staging. STUDY DESIGN: Retrospective review. METHODS: Seventy-one patients with initial diagnosis of head and neck squamous cell carcinoma having preoperative MR or CT imaging and PET/CT with subsequent bilateral neck dissection as part of primary treatment (142 neck dissections). Comparison of cervical nodal metastases based on three separate staging systems: preoperative CT and/or MRI scan, preoperative PET/CT, and pathology. RESULTS: Both CT/MRI scans and PET/CT scans statistically predicted pathologic outcomes (P = 0.0001, P = 0.0001, respectively) using Chi square analysis. There was a statistically significant improvement in the prediction of true pathologic disease using PET/CT compared to CT and/or MRI alone (P = 0.005). In a subgroup analysis including only the contralateral neck, this significance persisted (P = 0.013). McNemar's test revealed that subsequent detection of bilateral neck disease by PET/CT scan was significantly superior to MRI or CT alone (P = 0.023). CONCLUSION: In pathologically positive necks, PET/CT was statistically more reliable at identifying positive disease than CT or MRI alone. Furthermore, such a result is achieved without a statistically significant difference in false positivity between PET/CT and CT or MRI. This suggests that PET/CT positivity, despite negative clinical exam and CT/MRI findings, may be more likely to signify pathologic disease and require appropriate treatment.

VPAC1 receptors for imaging breast cancer: a feasibility study.

UNLABELLED: VPAC1 encodes G-protein-coupled receptors expressed on all breast cancer (BC) cells at the onset of the disease, but not on benign lesions. Our extensive preclinical studies have shown that (64)Cu-TP3805 has a high affinity for VPAC1, is stable in vivo, and has the ability to distinguish spontaneously grown malignant BC masses from benign lesions. Our long-term goal is to develop (64)Cu-TP3805 as an agent to perform in vivo histology, to distinguish malignant lesions from benign masses noninvasively and thereby avoid patient morbidity and the excess economic costs of benign biopsies. METHODS: (18)F-FDG obtained commercially served as a control. (64)Cu-TP3805 was prepared using a sterile kit containing 20 µg of TP3805. Radiochemical purity and sterility were examined. Nineteen consenting women with histologically proven BC were given 370 MBq of (18)F-FDG. One hour later, 6 of these patients were imaged with PET/CT and 13 with positron emission mammography (PEM). Two to 7 d later, 6 PET/CT patients received 111 MBq (± 10%) (n = 2), 127 MBq (± 10%) (n = 2), or 148 MBq (± 10%) (n = 2) of (64)Cu-TP3805 and were imaged 2 and 4 h later. Thirteen PEM patients received 148 MBq (± 10%) of (64)Cu-TP3805 and were imaged 15 min, 1 h, 2 h, and 4 h later. Standardized uptake value (SUV) was calculated for PET/CT patients, and PUV/BGV (PEM uptake value/background value) was calculated for PEM patients. Tumor volume was also calculated. RESULTS: The radiochemical purity of (64)Cu-TP3805 was 97% ± 2%, and specific activity was 44.4 GBq (1.2 Ci)/µmol. In 19 patients, a total of 24 lesions were imaged (15 invasive ductal carcinoma, 1 high-grade mammary carcinoma, 3 lobular carcinoma, 1 invasive papilloma, and 4 sentinel lymph nodes). All lesions were unequivocally detected by (64)Cu-TP3805 and by (18)F-FDG. The average tumor volume as determined by PET/CT with (64)Cu-TP3805 was 90.6% ± 16.1% of that with (18)F-FDG PET/CT, and the average SUV was 92% ± 26.4% of that with (18)F-FDG. For PEM, the tumor volume with (64)Cu-TP3805 was 113% ± 37% of that with (18)F-FDG and the PUV/BGV ratio was 97.7% ± 24.5% of that with (18)F-FDG. CONCLUSION: (64)Cu-TP3805 is worthy of further investigation in patients requiring biopsy of suggestive imaging findings, to further evaluate its ability to distinguish malignant lesions from benign masses noninvasively.

Altered drainage patterns in patients with melanoma and previous axillary dissection.

The incidence of melanoma is increasing rapidly in the United States. Sentinel lymph node biopsy is an important diagnostic tool in the treatment and staging of melanoma. However, many patients with melanoma will have had lymph node surgery for previous melanoma or breast cancer. We set out to examine alterations in drainage patterns in patients with previous axillary dissection for breast cancer. We reviewed four patients with truncal and/or extremity melanomas and examined their lymphoscintigraphy and drainage patterns. Three patients with truncal melanoma mapped to cervical lymph nodes and a fourth patient with an arm melanoma mapped to her previously dissected axilla. Sentinel lymph node mapping is still an important adjunct in patients with melanoma despite previous axillary dissection.

Somatostatin receptor scintigraphy in patients with metastatic uveal melanoma.

As uveal melanoma originates in the neural crest, we aimed to explore whether somatostatin receptor (SSTR) expression is present and plays any role in these patients. Heavily pretreated metastatic uveal melanoma patients were tested with somatostatin receptor scintigraphy (SRS). Planar images of the whole body complemented by single-photon emission computed tomography on suspected sites were acquired between 4 and 24 h after an intravenous administration of 185-222 MBq (5-6 mCi) of indium-octeotride. SSTR expression in metastatic tissues was confirmed by immunohistochemistry. In seven patients, sandostatin LAR was used with therapeutic intention. Thirty white patients were tested. All had extensive metastatic disease and the median number of previous treatments was three. SRS was found to be positive in 14 (46%) of the patients, but was not related to sex, type of previous treatments, tumor site, or histological type. In 10 patients, sufficient tumor specimens were available to perform immunohistochemical staining for SSTR. All cases with positive SSTR-2A staining were also positive by SRS. Two of the seven patients who received sandostatin LAR died within a month after receiving the first dose, whereas another two (28.5%) had stable disease for more than 5 months. The median time to progression after starting sandostatin was 2.1 months (range: 0.2-5.5 months). Approximately 50% of the uveal melanoma patients with extensive metastatic disease were positive for SSR, which was consistent with immunohistochemical staining for SSTR-2A. Therapeutic approaches targeting SSTR might be beneficial in patients with metastatic uveal melanoma.

Value of fluoro-2-deoxy-D-glucose-positron emission tomography for detecting metastatic lesions in head and neck cancer.

OBJECTIVES: The role of positron emission tomography (PET) scans in the staging of head and neck cancer (HNC) is unclear. The National Comprehensive Cancer Network guidelines do not recommend routine metastatic workup beyond physical examination, chest x-ray, and laboratory tests. The purpose of this report is to examine the accuracy of staging PET scans for detecting distant metastatic disease in patients with HNC. METHODS: Retrospective review of 182 consecutive newly diagnosed HNC patients who had a staging PET scan at Thomas Jefferson University Hospital between 2003 and 2007. RESULTS: The overall incidence of confirmed distant metastatic disease in this population was 5.0%. About 26 of the staging PET scans had areas suspicious for a metastatic lesion(s). Of total, 23 patients were further evaluated with imaging and/or biopsy, revealing 9 (39%) true positives, and 14 (60%) false positives. Of the 156 negative PET scans, there was 1 false negative and 155 true negatives. Thus, the sensitivity of PET was 90% and specificity was 92%. Positive predictive value was 39% and negative predictive value was 99.4%. No patients with pre-PET clinical stage I or II cancer had confirmed distant metastases. The only statistically significant predictor for metastatic disease was clinical stage IV versus all other stages (P=0.03). CONCLUSIONS: Given the marked differences in the treatment of locally advanced/nonmetastatic HNC versus metastatic HNC, we recommend PET for clinical stage IV disease. Although the sensitivity, specificity, and negative predictive value rates were acceptable, the positive predictive value was suboptimal. Patients found to have a PET scan "positive" for metastatic disease require confirmatory imaging or ideally biopsy.

Positron emission tomography for neck evaluation following definitive treatment with chemoradiotherapy for locoregionally advanced head and neck squamous cell carcinoma.

OBJECTIVES: The objective of the current review was to assess published data on the role of Positron Emission Tomography (PET) for evaluation of nodal residual disease after definitive chemoradiotherapy for head and neck squamous cell carcinoma (HNSCC). METHODS: Studies were identified by searching PubMed electronic databases. Only studies using a post-chemoradiotherapy PET for nodal residual disease evaluation were included in the present review. Both prospective and retrospective studies were included. Information regarding sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of PET for detecting nodal residual disease after definitive chemoradiotherapy for HNSCC was extracted and analyzed. RESULTS: Twenty published studies were included in the present review. Existing data suggest that a negative post-chemoradiotherapy PET scan is associated with a negative predictive value up to 100%. The sensitivity of PET in detecting nodal residual disease is greater for scans performed ≥ 10 weeks after definitive treatment with chemoradiotherapy for HNSCC. CONCLUSIONS: Further studies are needed to quantify the reliability of PET in detecting nodal residual disease after chemoradiotherapy for locoregionally advanced HNSCC. The optimal timing of PET imaging after chemoradiotherapy remains to be defined.