Peter L Choyke

NCI-Frederick, Maryland, United States

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Publications (650)2615.51 Total impact

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    ABSTRACT: We determined the prostate cancer detection rate of multiparametric magnetic resonance imaging at 3T. Precise one-to-one histopathological correlation with magnetic resonance imaging was possible using prostate magnetic resonance imaging based custom printed specimen molds after radical prostatectomy. This institutional review board approved prospective study included 45 patients (mean age 60.2 years, range 49 to 75) with a mean prostate specific antigen of 6.37 ng/ml (range 2.3 to 23.7) who had biopsy proven prostate cancer (mean Gleason score of 6.7, range 6 to 9). Before prostatectomy all patients underwent prostate magnetic resonance imaging using endorectal and surface coils on a 3T scanner, which included triplane T2-weighted magnetic resonance imaging, apparent diffusion coefficient maps of diffusion weighted magnetic resonance imaging, dynamic contrast enhanced magnetic resonance imaging and spectroscopy. The prostate specimen was whole mount sectioned in a customized mold, allowing geometric alignment to magnetic resonance imaging. Tumors were mapped on magnetic resonance imaging and histopathology. Sensitivity, specificity, positive predictive value and negative predictive value of magnetic resonance imaging for cancer detection were calculated. In addition, the effects of tumor size and Gleason score on the sensitivity of multiparametric magnetic resonance imaging were evaluated. The positive predictive value of multiparametric magnetic resonance imaging to detect prostate cancer was 98%, 98% and 100% in the overall prostate, peripheral zone and central gland, respectively. The sensitivity of magnetic resonance imaging sequences was higher for tumors larger than 5 mm in diameter as well as for those with higher Gleason scores (greater than 7, p <0.05). Prostate magnetic resonance imaging at 3T allows for the detection of prostate cancer. A multiparametric approach increases the predictive power of magnetic resonance imaging for diagnosis. In this study accurate correlation between multiparametric magnetic resonance imaging and histopathology was obtained by the patient specific, magnetic resonance imaging based mold technique.
    The Journal of urology 09/2011; 186(5):1818-24. · 3.75 Impact Factor
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    ABSTRACT: Diffusion-weighted magnetic resonance imaging (MRI), which involves the acquisition of a magnetic resonance signal related to the Brownian motion of water protons in tissue, has become a useful technique for assessing tumors. In this article, we review the basic concepts, imaging strategies, and body applications of diffusion-weighted MRI in detecting and monitoring cancer.
    Diagnostic and interventional radiology (Ankara, Turkey) 09/2011; 18(1):46-59. · 1.03 Impact Factor
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    ABSTRACT: Prostate cancer is the most common cancer among American men. It varies widely in aggressiveness, ranging from completely indolent to highly aggressive. Currently, predicting the natural history of a particular tumor and deciding on the appropriate treatment, which might include active surveillance, surgery, radiation or hormonal therapies, are based on the condition and age of the patient as well as the presumed stage of the disease. Imaging plays an important role in staging localized prostate cancer. Magnetic resonance imaging (MRI) best depicts the zonal anatomy, with a superior soft tissue resolution providing better results for tumor localization, monitoring, and local staging. Previously, the major function of prostate MRI has been in staging, and this role remains important. In this article, we introduce the reader to the expanding roles that MRI plays in the management of localized prostate cancer.
    Diagnostic and interventional radiology (Ankara, Turkey) 09/2011; 18(1):34-45. · 1.03 Impact Factor
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    ABSTRACT: Autosomal recessive polycystic kidney disease (ARPKD), characterized by progressive cystic degeneration of the kidneys and congenital hepatic fibrosis (CHF), is the most common childhood onset ciliopathy, with an estimated frequency of 1 in 20,000 births. It is caused by mutations in PKHD1. The carrier frequency for ARPKD in the general population is estimated at 1 in 70. Given the recessive inheritance pattern, individuals who are heterozygous for PKHD1 mutations are not expected to have clinical findings. We performed ultrasound (USG) evaluations on 110 parents from 64 independent ARPKD families and identified increased medullary echogenicity in 6 (5.5%) and multiple small liver cysts in 10 parents (9%). All ARPKD parents with these abnormal imaging findings were asymptomatic; kidney and liver function tests were unremarkable. Complete sequencing of PKHD1 in the 16 ARPKD parents with abnormal imaging confirmed the mutation transmitted to the proband, but did not reveal any other pathogenic variants. Our data suggest that carrier status for ARPKD is a predisposition to polycystic liver disease and renal involvement associated with increased medullary echogenicity on USG. Whether some of these individuals become symptomatic as they age remains to be determined.
    Molecular Genetics and Metabolism 09/2011; 104(4):677-81. · 2.83 Impact Factor
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    ABSTRACT: The ability to control the growth of new blood vessels would be an extraordinary therapeutic tool for many disease processes. Too often, the promises of discoveries in the basic science arena fail to translate to clinical success. While several anti angiogenic therapeutics are now FDA approved, the envisioned clinical benefits have yet to be seen. The ability to clinically non-invasively image angiogenesis would potentially be used to identify patients who may benefit from anti-angiogenic treatments, prognostication/risk stratification and therapy monitoring. This article reviews the current and future prospects of implementing angiogenesis imaging in the clinic.
    Imaging in medicine 09/2011; 3(4):445-457.
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    ABSTRACT: (18)F-fluoropaclitaxel is a radiolabeled form of paclitaxel, a widely used chemotherapy agent. Preclinical data suggest that (18)F-fluoropaclitaxel may be a reasonable surrogate for measuring the uptake of paclitaxel. As a substrate of P-glycoprotein, a drug efflux pump associated with multidrug resistance, (18)F-fluoropaclitaxel may also be useful in identifying multidrug resistance and predicting tumor response for drugs other than paclitaxel. After informed consent was obtained, 3 healthy volunteers and 3 patients with untreated breast cancer (neoadjuvant chemotherapy candidates, tumor size > 2 cm) received an intravenous infusion of (18)F-fluoropaclitaxel and then underwent PET/CT. Healthy volunteers underwent serial whole-body imaging over an approximately 3-h interval, and organ (18)F residence times were determined from the time-activity curves uncorrected for decay to determine dosimetry. Radiation dose estimates were calculated using OLINDA/EXM software. For breast cancer patients, dynamic imaging of the primary tumor was performed for 60 min, followed by static whole-body scans at 1 and 2 h after injection. Dosimetry calculations showed that the gallbladder received the highest dose (229.50 μGy/MBq [0.849 rad/mCi]), followed by the small and large intestines (161.26 μGy/MBq [0.597 rad/mCi] and 184.59 μGy/MBq [0.683 rad/mCi]). The resultant effective dose was 28.79 μGy/MBq (0.107 rem/mCi). At approximately 1 h after injection, an average of 42% of the decay-corrected activity was in the gastrointestinal system, with a mean of 0.01% in the tumor. All 3 breast cancer patients showed retention of (18)F-fluoropaclitaxel and ultimately demonstrated a complete pathologic response (no invasive cancer in the breast or axillary nodes) to chemotherapy that included a taxane (either paclitaxel or docetaxel) at surgical resection. The tumor-to-background ratio increased with time to a maximum of 7.7 at 20 min. This study demonstrates the feasibility of using (18)F-fluoropaclitaxel PET/CT tumor imaging and provides radiation dosimetry measurements in humans. Although further study is needed, it is hoped that the measured intratumoral (18)F-fluoropaclitaxel distribution can serve as a surrogate for paclitaxel, and potentially other chemotherapeutic agent retention, in solid tumors.
    Journal of Nuclear Medicine 08/2011; 52(9):1339-45. · 5.77 Impact Factor
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    ABSTRACT: In patients with prostate cancer, a positive surgical margin is associated with an increased risk of cancer recurrence and poorer outcome, yet margin status cannot be determined during the surgery. An in vivo optical imaging probe that could identify the tumor margins during surgery could result in improved outcomes. The design of such a probe focuses on a highly specific targeting moiety and a near-infrared (NIR) fluorophore that is activated only when bound to the tumor. In this study, we successfully synthesized an activatable monoclonal antibody-fluorophore conjugate consisting of a humanized anti-Prostate-Specific Membrane Antigen (PSMA) antibody (J591) linked to an indocyanine green (ICG) derivative. Prior to binding to PSMA and cellular internalization, the conjugate yielded little light; however, after binding an 18-fold activation was observed permitting the specific detection of PSMA+ tumors up to 10 days after injection of a low dose (0.25 mg/kg) of the reagent. This agent demonstrates promise as a method to image the extent of prostate cancer in vivo and could assist with real-time resection of extracapsular extension of tumor and positive lymph nodes.
    Bioconjugate Chemistry 08/2011; 22(8):1700-5. · 4.58 Impact Factor
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    ABSTRACT: A novel platform was developed that fuses pre-biopsy magnetic resonance imaging with real-time transrectal ultrasound imaging to identify and biopsy lesions suspicious for prostate cancer. The cancer detection rates for the first 101 patients are reported. This prospective, single institution study was approved by the institutional review board. Patients underwent 3.0 T multiparametric magnetic resonance imaging with endorectal coil, which included T2-weighted, spectroscopic, dynamic contrast enhanced and diffusion weighted magnetic resonance imaging sequences. Lesions suspicious for cancer were graded according to the number of sequences suspicious for cancer as low (2 or less), moderate (3) and high (4) suspicion. Patients underwent standard 12-core transrectal ultrasound biopsy and magnetic resonance imaging/ultrasound fusion guided biopsy with electromagnetic tracking of magnetic resonance imaging lesions. Chi-square and within cluster resampling analyses were used to correlate suspicion on magnetic resonance imaging and the incidence of cancer detected on biopsy. Mean patient age was 63 years old. Median prostate specific antigen at biopsy was 5.8 ng/ml and 90.1% of patients had a negative digital rectal examination. Of patients with low, moderate and high suspicion on magnetic resonance imaging 27.9%, 66.7% and 89.5% were diagnosed with cancer, respectively (p <0.0001). Magnetic resonance imaging/ultrasound fusion guided biopsy detected more cancer per core than standard 12-core transrectal ultrasound biopsy for all levels of suspicion on magnetic resonance imaging. Prostate cancer localized on magnetic resonance imaging may be targeted using this novel magnetic resonance imaging/ultrasound fusion guided biopsy platform. Further research is needed to determine the role of this platform in cancer detection, active surveillance and focal therapy, and to determine which patients may benefit.
    The Journal of urology 08/2011; 186(4):1281-5. · 3.75 Impact Factor
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    ABSTRACT: Intravenously administered radiolabeled peptides targeting somatostatin receptors are used for the treatment of unresectable gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Recently, we demonstrated a high first-pass effect during intra-arterial (i.a.) administration of positron emission tomography (PET) labeled (68)Ga-DOTA(0)-d-Phe(1)-Tyr(3)-octreotide (DOTATOC). In this pilot study, we investigated the therapeutic effectiveness of arterial administered DOTATOC, labeled with the therapeutic β emitters (90)Y and (177)Lu. (90)Y- and/or (177)Lu-DOTATOC were infused into the hepatic artery of 15 patients with liver metastases arising from GEP-NETs. Response was assessed using DOTATOC-PET, multiphase contrast enhanced computed tomography, magnetic resonance imaging, and the serum tumor marker chromogranin A. Pharmacokinetic data of the arterial approach were assessed using (111)In-DOTATOC scans. With the treatment regime of this pilot study, complete remission was achieved in one (7%) patient and partial remission was observed in eight (53%) patients, six patients were classified as stable (40%; response evaluation criteria in solid tumors criteria). The concomitant decrease of elevated serum tumor marker confirmed the radiologic response. Median time to progression was not reached within a mean follow-up period of 20 months. Receptor saturation and redistribution effects were identified as limiting factors for i.a. DOTATOC therapy. The high rate of objective radiologic response in NET patients treated with arterial infusion of (90)Y-/(177)Lu-DOTATOC compares favorably with systemic chemotherapy and intravenous radiopeptide therapy. While i.a. DOTATOC therapy is only applicable to patients with tumors of limited anatomic distribution, the results of this pilot study are a promising development in the treatment of GEP-NET and warrants further investigation of this novel approach.
    Endocrine Related Cancer 07/2011; 18(5):595-602. · 5.26 Impact Factor
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    ABSTRACT: In vivo dynamic contrast-enhanced imaging tools provide non-invasive methods for analyzing various functional changes associated with disease initiation, progression and responses to therapy. The quantitative application of these tools has been hindered by its inability to accurately resolve and characterize targeted tissues due to spatially mixed tissue heterogeneity. Convex Analysis of Mixtures - Compartment Modeling (CAM-CM) signal deconvolution tool has been developed to automatically identify pure-volume pixels located at the corners of the clustered pixel time series scatter simplex and subsequently estimate tissue-specific pharmacokinetic parameters. CAM-CM can dissect complex tissues into regions with differential tracer kinetics at pixel-wise resolution and provide a systems biology tool for defining imaging signatures predictive of phenotypes. The MATLAB source code can be downloaded at the authors' website Supplementary data are available at Bioinformatics online.
    Bioinformatics 07/2011; 27(18):2607-9. · 5.47 Impact Factor
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    ABSTRACT: Radiolabeling of a monoclonal antibody (mAb) with a metallic radionuclide requires the conjugation of a bifunctional chelator to the mAb. The conjugation, however, can alter the physical and immunological properties of the mAb, consequently affecting its tumor-targeting pharmacokinetics. In this study, we investigated the effect of the amount of 2-(p-isothiocyanatobenzyl)-cyclohexyl-diethylenetriamine-pentaacetic acid (CHX-A″) conjugated to MORAb-009, a mAb directed against mesothelin, and the effect of MORAb dose on the biodistribution of (111)In-labeled MORAb-009. We used nude mice bearing the A431/K5 tumor as a mesothelin-positive tumor model and the A431 tumor as a mesothelin-negative control. To find the optimal level of CHX-A″ conjugation, CHX-A″-MORAb-009 conjugates with 2.4, 3.5 and 5.5 CHX-A″ molecules were investigated. To investigate the effect of injected MORAb-009 dose on neutralizing the shed mesothelin in the circulation, biodistribution studies were performed after the intravenous co-injection of (111)In-labeled MORAb-009 (2.4 CHX-A″/MORAb-009) with three different doses: 0.2, 2 and 30 μg of MORAb-009. The tumor uptake in A431/K5 tumor was four times higher than that in A431 tumor, indicating that the tumor uptake in A431/K5 was mesothelin mediated. The conjugate with 5.5 CHX-A″ showed a lower isoelectric point (pI) and lower immunoreactivity (IR) than the 2.4 CHX-A″ conjugate. These differences were reflected in the biodistribution of the (111)In label. The (111)In-labeled MORAb-009 conjugated with 2.4 CHX-A″ produced higher tumor uptake and lower liver and spleen uptakes than the 5.5 CHX-A″ conjugate. The biodistribution studies also revealed that the tumor uptake was significantly affected by the injected MORAb-009 dose and tumor size. The 30-μg dose produced higher tumor uptake than the 0.2- and 2-μg doses, whereas the 30-μg dose produced lower liver and spleen uptakes than the 0.2-μg dose. This study demonstrates that the number of chelate conjugation and the injected dose are two important parameters to achieve high tumor and low non-target organ uptake of (111)In-labeled MORAb-009. This study also suggests that the injected dose of mAb could be individualized based on the tumor size or the blood level of shed antigen in a patient to achieve the ideal tumor-to-organ radioactivity ratios.
    Nuclear Medicine and Biology 07/2011; 38(8):1119-27. · 2.52 Impact Factor
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    Peter L Choyke
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    ABSTRACT: Mittra et al (1) describe a new positron emission tomographic (PET) radiopharmaceutical, fluorine 18 ((18)F) 2-fl uoropropionyl labeled PEGylated dimeric RGD peptide (FPPRGD2), a marker of α(v)β(3) integrin expression, which they tested in fi ve healthy volunteers. No adverse events were encountered, and the biodistribution suggested both a renal and a hepatobiliary excretory route. This early safety testing paves the way for future studies of patients with cancer who are undergoing antiangiogenic therapies. (18)F-FPPRGD2 represents one of several integrin imaging agents that are moving closer to clinical reality.
    Radiology 07/2011; 260(1):1-2. · 6.34 Impact Factor
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    ABSTRACT: The processes of tumor invasion and metastasis have been well characterized at the molecular level, and numerous biomarkers of tumor aggressiveness have been discovered. Molecular imaging offers the opportunity to depict specific cell markers relevant to tumor aggressiveness. Here, we describe the role of MRI in identifying tumor invasiveness and metastasis with reference to other methods. Target-specific molecular imaging probes for tumor invasiveness have been developed for positron emission tomography and optical imaging, but progress in MRI has been slower. For example, proteases associated with tumor invasion, such as specific matrix metalloproteinases or cathepsins, can be targeted in vivo using optical and positron emission tomography methods, but have not yet been successful with MRI. In addition, we describe the use of MRI to detect metastases. Novel MR contrast agents based on iron oxide and dendrimer nanomaterials allow for better characterization of tumor metastases. Organ-specific MR contrast agents are used to identify metastatic disease in the liver. Finally, diffusion-weighted whole-body MRI is discussed as an alternative offered by MRI that does not require the use of molecular probes to screen distant metastases.
    NMR in Biomedicine 07/2011; 24(6):561-8. · 3.45 Impact Factor
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    ABSTRACT: Autosomal dominant (ADPKD) and recessive (ARPKD) polycystic kidney diseases are the most common hepatorenal fibrocystic diseases (ciliopathies). Characteristics of liver disease of these disorders are quite different. All of the patients with ARPKD have congenital hepatic fibrosis (CHF) often complicated by portal hypertension. In contrast, typical liver involvement in ADPKD is polycystic liver disease, although rare atypical cases with CHF are reported. Our goal was to describe the characteristics of CHF in ADPKD. As a part of an intramural study of the National Institutes of Health on ciliopathies (, trial NCT00068224), we evaluated 8 patients from 3 ADPKD families with CHF. We present their clinical, biochemical, imaging, and PKD1 and PKHD1 sequencing results. In addition, we tabulate the characteristics of 15 previously reported patients with ADPKD-CHF from 11 families. In all of the 19 patients with ADPKD-CHF (9 boys, 10 girls), portal hypertension was the main manifestation of CHF; hepatocelllular function was preserved and liver enzymes were largely normal. In all of the 14 families, CHF was not inherited vertically, that is the parents of the index cases had PKD but did not have CHF-suggesting modifier gene(s). Our 3 families had pathogenic mutations in PKD1; sequencing of the PKHD1 gene as a potential modifier did not reveal any mutations. Characteristics of CHF in ADPKD are similar to CHF in ARPKD. ADPKD-CHF is caused by PKD1 mutations, with probable contribution from modifying gene(s). Given that both boys and girls are affected, these modifier(s) are likely located on autosomal chromosome(s) and less likely X-linked.
    Journal of pediatric gastroenterology and nutrition 06/2011; 54(1):83-9. · 2.18 Impact Factor
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    ABSTRACT: The expanded biological and medical applications of nanomaterials place a premium on better understanding of the chemical and physical determinants of in vivo particles. Nanotechnology allows us to design a vast array of molecules with distinct chemical and biological characteristics, each with a specific size, charge, hydrophilicity, shape, and flexibility. To date, much research has focused on the role of particle size as a determinant of biodistribution and clearance. Additionally, much of what we know about the relationship between nanoparticle traits and pharmacokinetics has involved research limited to the gross average hydrodynamic size. Yet, other features such as particle shape and flexibility affect in vivo behavior and become increasingly important for designing and synthesizing nanosized molecules. Herein, we discuss determinants of in vivo behavior of nanosized molecules used as imaging agents with a focus on dendrimer-based contrast agents. We aim to discuss often overlooked or, yet to be considered, factors that affect in vivo behavior of synthetic nanosized molecules, as well as aim to highlight important gaps in current understanding.
    Bioconjugate Chemistry 06/2011; 22(6):993-1000. · 4.58 Impact Factor
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    ABSTRACT: Hypoxia-inducible factor 1 (HIF-1) α is frequently overexpressed in human tumors and is associated with angiogenesis and metastasis. Topotecan, a topoisomerase I inhibitor, has been shown to inhibit HIF-1α expression in preclinical models. We designed a pilot trial to measure HIF-1α inhibition in tumor biopsies from patients with advanced solid tumors overexpressing HIF-1α, after treatment with oral topotecan. Topotecan was administered orally at 1.6 mg/m(2) once daily for 5 days/week for 2 weeks, in 28-day cycles. Objectives were to determine inhibition of expression of HIF-1α and HIF-1 target genes in tumor; to assess tumor blood flow by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI); and to measure pharmacokinetics. Tumor biopsies were collected at baseline and during the second cycle of treatment. Sixteen patients were enrolled. The dose of topotecan was reduced to 1.2 mg/m(2)/day due to myelosuppression. Seven patients had paired tumor biopsies. In 4 patients, HIF-1α nuclear staining became undetectable after treatment (7.5%-50% staining at baseline). Decreased levels of VEGF and GLUT-1 mRNA were measured in 4 patients; the changes were concordant with reduction in HIF-1α in 3 patients. Decreased tumor blood flow and permeability were observed by DCE-MRI in 7 of 10 patients after 1 cycle. One patient had a partial response accompanied by inhibition of HIF-1α in tumor and reduction in tumor blood flow on DCE-MRI. This multihistology, target assessment trial of a small molecule inhibitor of HIF-1α showed that topotecan could decrease HIF-1α expression in advanced solid tumors.
    Clinical Cancer Research 06/2011; 17(15):5123-31. · 7.84 Impact Factor
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    ABSTRACT: Traditionally, the skeletal survey has been the standard modality for the detection of osteolytic bone disease in multiple myeloma. In addition to its poor sensitivity for the detection of osteolytic lesions, this modality is not able to identify extramedullary lesions and focal bone marrow involvement, nor measure response to therapy. The application of novel imaging techniques such as computed tomography (CT), magnetic resonance imaging (MRI), and molecular imaging such as fluorine-18 fluorodeoxyglucose positron emission tomography CT ((18)F-FDG PET/CT) and fluorine-18 sodium fluoride positron emission tomography CT ((18)F-NaF PET/CT) has the potential to overcome these limitations as well as provide prognostic information in precursor states and multiple myeloma. Also promising is the use of dynamic contrast enhanced magnetic resonance imaging (DCE MRI) to measure vascular permeability, an important feature of myelomagenesis. This review summarizes the current status and possible future role of novel imaging modalities in multiple myeloma and its precursor states.
    Leukemia & lymphoma 06/2011; 52(9):1630-40. · 2.61 Impact Factor
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    ABSTRACT: Stimulating an immune response against cancer with the use of vaccines remains a challenge. We hypothesized that combining a melanoma vaccine with interleukin-2, an immune activating agent, could improve outcomes. In a previous phase 2 study, patients with metastatic melanoma receiving high-dose interleukin-2 plus the gp100:209-217(210M) peptide vaccine had a higher rate of response than the rate that is expected among patients who are treated with interleukin-2 alone. We conducted a randomized, phase 3 trial involving 185 patients at 21 centers. Eligibility criteria included stage IV or locally advanced stage III cutaneous melanoma, expression of HLA*A0201, an absence of brain metastases, and suitability for high-dose interleukin-2 therapy. Patients were randomly assigned to receive interleukin-2 alone (720,000 IU per kilogram of body weight per dose) or gp100:209-217(210M) plus incomplete Freund's adjuvant (Montanide ISA-51) once per cycle, followed by interleukin-2. The primary end point was clinical response. Secondary end points included toxic effects and progression-free survival. The treatment groups were well balanced with respect to baseline characteristics and received a similar amount of interleukin-2 per cycle. The toxic effects were consistent with those expected with interleukin-2 therapy. The vaccine-interleukin-2 group, as compared with the interleukin-2-only group, had a significant improvement in centrally verified overall clinical response (16% vs. 6%, P=0.03), as well as longer progression-free survival (2.2 months; 95% confidence interval [CI], 1.7 to 3.9 vs. 1.6 months; 95% CI, 1.5 to 1.8; P=0.008). The median overall survival was also longer in the vaccine-interleukin-2 group than in the interleukin-2-only group (17.8 months; 95% CI, 11.9 to 25.8 vs. 11.1 months; 95% CI, 8.7 to 16.3; P=0.06). In patients with advanced melanoma, the response rate was higher and progression-free survival longer with vaccine and interleukin-2 than with interleukin-2 alone. (Funded by the National Cancer Institute and others; number, NCT00019682.).
    New England Journal of Medicine 06/2011; 364(22):2119-27. · 54.42 Impact Factor
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    ABSTRACT: In recent years, numerous in vivo molecular imaging probes have been developed. As a consequence, much has been published on the design and synthesis of molecular imaging probes focusing on each modality, each type of material, or each target disease. More recently, second generation molecular imaging probes with unique, multi-functional, or multiplexed characteristics have been designed. This critical review focuses on (i) molecular imaging using combinations of modalities and signals that employ the full range of the electromagnetic spectra, (ii) optimized chemical design of molecular imaging probes for in vivo kinetics based on biology and physiology across a range of physical sizes, (iii) practical examples of second generation molecular imaging probes designed to extract complementary data from targets using multiple modalities, color, and comprehensive signals (277 references).
    Chemical Society Reviews 05/2011; 40(9):4626-48. · 24.89 Impact Factor
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    ABSTRACT: Overexpression of HER2/neu in breast cancer is correlated with a poor prognosis. It may vary between primary tumors and metastatic lesions and change during the treatment. Therefore, there is a need for a new means to assess HER2/neu expression in vivo. In this work, we used (68)Ga-labeled DOTA-Z(HER2:2891)-Affibody to monitor HER2/neu expression in a panel of breast cancer xenografts. DOTA-Z(HER2:2891)-Affibody molecules were labeled with (68)Ga. In vitro binding was characterized by a receptor saturation assay. Biodistribution and PET imaging studies were conducted in athymic nude mice bearing subcutaneous human breast cancer tumors with three different levels of HER2/neu expression. Nonspecific uptake was analyzed using non-HER2-specific Affibody molecules. Signal detected by PET was compared with ex vivo assessment of the tracer uptake and HER2/neu expression. The (68)Ga-DOTA-Z(HER2:2891)-Affibody probe showed high binding affinity to MDA-MB-361 cells (K (D) = 1.4 ± 0.19 nM). In vivo biodistribution and PET imaging studies demonstrated high radioactivity uptake in HER2/neu-positive tumors. Tracer was eliminated quickly from the blood and normal tissues, resulting in high tumor-to-blood ratios. The highest concentration of radioactivity in normal tissue was seen in the kidneys (227 ± 14%ID/g). High-contrast PET images of HER2/neu-overexpressing tumors were recorded as soon as 1 h after tracer injection. A good correlation was observed between PET imaging, biodistribution estimates of tumor tracer concentration, and the receptor expression. These results suggest that PET imaging using (68)Ga-DOTA-Z(HER2:2891)-Affibody is sensitive enough to detect different levels of HER2/neu expression in vivo.
    European Journal of Nuclear Medicine 04/2011; 38(11):1967-76. · 4.53 Impact Factor

Publication Stats

16k Citations
2,615.51 Total Impact Points


  • 2001–2014
    • NCI-Frederick
      • Laboratory of Pathology
      Maryland, United States
  • 1990–2014
    • National Institutes of Health
      • • Center for Cancer Research
      • • Laboratory of Pathology
      • • Center for Interventional Oncology
      • • Branch of Metabolism
      Maryland, United States
  • 1970–2014
    • National Cancer Institute (USA)
      • • Molecular Imaging Program
      • • Laboratory of Pathology
      • • Genetic Epidemiology
      • • Surgery Branch
      Maryland, United States
  • 2013
    • University of Helsinki
      Helsinki, Southern Finland Province, Finland
    • The Jikei University School of Medicine
      • Department of Internal Medicine H
      Tokyo, Tokyo-to, Japan
  • 1998–2013
    • Leidos Biomedical Research
      Maryland, United States
    • University of Pennsylvania
      Philadelphia, Pennsylvania, United States
  • 2012
    • Texas Christian University
      • Department of Chemistry
      Fort Worth, TX, United States
    • Aarhus University Hospital
      • Department of Nuclear Medicine & PET-Centre
      Århus, Central Jutland, Denmark
  • 2004–2012
    • Virginia Polytechnic Institute and State University
      • Department of Electrical and Computer Engineering
      Blacksburg, VA, United States
  • 2011
    • Osaka Prefecture University
      • Nanoscience and Nanotechnology Research Center
      Sakai, Osaka-fu, Japan
    • Conselleria de Sanidade
      La Corogne, Galicia, Spain
    • United States Army
      Washington, West Virginia, United States
  • 2010–2011
    • University of Copenhagen
      • Department of Clinical Biochemistry
      København, Capital Region, Denmark
    • Boston Children's Hospital
      Boston, Massachusetts, United States
  • 2007–2011
    • The University of Tokyo
      • • Faculty & Graduate School of Medicine
      • • Faculty and Graduate School of Pharmaceutical Sciences
      Tokyo, Tokyo-to, Japan
    • Howard Hughes Medical Institute
      Ashburn, Virginia, United States
    • Virginia State University
      Petersburg, Virginia, United States
    • University of South Dakota
      Vermillion, South Dakota, United States
  • 2006–2010
    • National Human Genome Research Institute
      Maryland, United States
  • 2008
    • Roswell Park Cancer Institute
      • Department of Radiation Medicine
      Buffalo, New York, United States
  • 2007–2008
    • Philips
      Eindhoven, North Brabant, Netherlands
  • 2003–2004
    • Robert Wood Johnson University Hospital
      New Brunswick, New Jersey, United States
    • The Ohio State University
      • Department of Radiology
      Columbus, OH, United States
    • CSU Mentor
      Long Beach, California, United States
  • 2000–2004
    • Uniformed Services University of the Health Sciences
      • • Department of Radiology & Radiological Sciences
      • • Department of Radiobiology
      Bethesda, MD, United States
  • 1986–2004
    • Georgetown University
      • Department of Radiology
      Washington, D. C., DC, United States
    • Hospital of the University of Pennsylvania
      • Department of Radiology
      Philadelphia, PA, United States
  • 2002
    • National Eye Institute
      Maryland, United States
    • George Mason University
      • Department of Computational and Data Sciences
      Fairfax, VA, United States
  • 1999–2002
    • GE India Industrial Pvt. Ltd.
      New Dilli, NCT, India
  • 1996
    • University of Alabama in Huntsville
      • Department of Computer Science
      Huntsville, Alabama, United States
  • 1995
    • Henry M Jackson Foundation
      Maryland City, Maryland, United States
  • 1992
    • The National Institute of Diabetes and Digestive and Kidney Diseases
      Maryland, United States