Peter L Choyke

NCI-Frederick, Maryland, United States

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Publications (656)2711.56 Total impact

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    ABSTRACT: Optical imaging is emerging as an important tool to visualize tumors. However, there are many potential choices among the available fluorophores. Optical imaging probes that emit in the visible range can image superficial tumors with high quantum yields; however, if deeper imaging is needed then near-infrared (NIR) fluorophores are necessary. Most commercially available NIR fluorophores are cyanine based and are prone to nonspecific binding and relatively limited photostability. Silica-containing rhodamine (SiR) fluorophores represent a new class of NIR fluorophores, which permit photoactivation via H-dimer formation as well as demonstrate improved photostability. This permits higher tumor-to-background ratios (TBRs) to be achieved over longer periods of time. Here, we compared an avidin conjugated with SiR700 (Av-SiR700) to similar compounds based on cyanine dyes (Av-Cy5.5 and Av-Alexa Fluor 680) in a mouse tumor model of ovarian cancer metastasis. We found that the Av-SiR700 probe demonstrated superior quenching, enabling activation after binding-internalization to the target cell. As a result, Av-SiR700 had higher TBRs compared to Av-Cy5.5 and better biostability compared to Av-Alexa Fluor 680.
    Bioconjugate Chemistry 12/2011; 22(12):2531-8. · 4.82 Impact Factor
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    ABSTRACT: PURPOSE For the improvement of adoptive immune cell therapies, increased knowledge on the behavior of the transferred cells and their ultimate fate in vivo is essential. The aim of the present study is to evaluate a FDA approved ultrasmall superparamagnetic iron oxide (USPIO), Feromoxytol, for T cell labeling and to demonstrate by MRI the targeting of cytotoxic T cells to the tumors expressing the specific antigen, following an adoptive transfer, in a simple murine model system. METHOD AND MATERIALS CD8 T cells specific to ovalbumin (OVA) were isolated from spleens of OT1 transgenic mice. In order to determine the optimal conditions for effective T cell labeling, CD8 T cells were incubated with 0 or 5 µg/mL of protamine sulfate (PS) and USPIO at different iron concentrations ranging from 0 to 100 µg/mL and viability of the labeled cells were examined by Trypan blue staining. OT1 CD8 T cells labeled with USPIO-PS complex were adoptively transferred into Rag1 KO mice bearing intra-muscular OVA-expressing B16-F melanoma (B16-OVA) tumor and control non-OVA expressing B16-F (B16) tumor in both thighs. Migrations of T cells were tracked in vivo by 3 T MRI 24 h after the transfer. RESULTS MRI measurements of labeled T cells revealed the strongest signal reduction in cells incubated with 100 µg/mL of USPIO and 5 µg/mL of PS for 2 h, with no significatn cell death seen. MRI showed significant decrease of signal intensity (SI) within the B16-OVA tumor and its adjacent lymph node due to the accumulation of USPIO-PS labeled OT-I CD8 T cells in these tissues when compared to the control B16 tumor and its adjacent lymph node in the contra-lateral side (Figure 1). In addition, a significant decrease in the SI in the spleen was demonstrated, as the spleen is a major organ to which T cells migrate after an adoptive transfer. No SI change within the liver was shown, indicating the absence of free USPIO particles. CONCLUSION These results indicated that: 1) T cells could be effectively labeled with USPIO-PS with an incubation time of 2 hr and efficient USPIO labeling of these cells requires PS; 2) We also demonstrated, for the first time, imaging of USPIO labeled cytotoxic T cells specifically targeting to tumors in vivo. CLINICAL RELEVANCE/APPLICATION Efficient labeling of functionally active T lymphocytes and their detection by MRI allows the in vivo monitoring of T cells and, subsequently, would contribute to the improvements of immuno therapy.
    Radiological Society of North America 2011 Scientific Assembly and Annual Meeting; 11/2011
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    ABSTRACT: LEARNING OBJECTIVES 1. Appreciate the status of prostate cancer care in the PSA screening era and the limitations of current therapeutic approaches 2. Become familiar with the current prostate cancer care guidelines 3. Know the indications for prostate MRI 4. Become familiar with scenarios where MRI has been helpful in prostate cancer management from diagnosis and biopsy to therapy 5. Appreciate the issues related to implementation of MRI in different health care systems
    Radiological Society of North America 2011 Scientific Assembly and Annual Meeting; 11/2011
  • Peter L. Choyke
    Radiological Society of North America 2011 Scientific Assembly and Annual Meeting; 11/2011
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    ABSTRACT: PURPOSE/AIM The purpose of the exhibit is to: -Review the basic science of F18-NaF as a radiotracer -Showcase various findings on NaF PET/CT scans in a correlative atlas format, in order to increase awareness of their appearance on these scans -Illustrate the differences in interpretation strategies between NaF PET/CT and routine Tc99m bone scans CONTENT ORGANIZATION -NaF background and history -Recent trends, reimbursement -Differences between Tc-99m and NaF imaging -Benign findings: Fractures Hemangioma DJD Osteonecrosis of the jaw Subchondral cyst Orthopedic screw/hardware loosening -Malignant findings: Varying uptake in multiple myeloma Discordant FDG vs NaF in breast cancer Prostate cancer Lung cancer -Interpretive, procedural and reporting recommendations SUMMARY The major teaching points of this exhibit are to: Become familiar with the appearance of select benign and malignant lesions on NaF PET/CT bone scans Illustrate the differences in the interpretation of NaF PET/CT vs. Tc99m bone scans, including the use of SUV Appreciate the effect that the acquisition protocol can have on image interpretation of NaF scans Recognize the need for careful clinical and CT correlation of NaF findings
    Radiological Society of North America 2011 Scientific Assembly and Annual Meeting; 11/2011
  • Noriko Sato, Omer Aras, Peter L. Choyke
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    ABSTRACT: PURPOSE The aim of this study is to examine the potential of a near-infrared (NIR) fluorescent probe with phosphstidylserin binding motif to visualize tumor killing effect of cytotoxic T cells in a murine immune cell therapy model. METHOD AND MATERIALS A NIR probe PSVue 794 (Em 810 nm) binds to anionic phospholipids, including phosphatidylserine, via its zinc(II)-dipocilylamine motif. To examine if PSVue 794 allows visualization of cancer cell death induced by tumor specific cytotoxic T cells, adoptive transfer of CD8 T cells was employed in a mouse tumor model. CD8 T cells specific for obalbumin (OVA) were obtained from OT-1 T cell receptor transgenic mice. After labeling of OT-1 CD8 T cells with cell-permeable far-red DDAO dye (DDAO, Em 655nm) for tracking purpose, T cells were transferred to recipient mice bearing an intramascular OVA-expressing thymoma (EG.7) and the parental OVA-non-expressing thymoma (EL4) in the thigh. Twelve hours later, PSVue 794 (4mg/kg) was injected intravenously and optical images were acquired up to 5 days after the injection. Binding of PSVue 794 to apoptotic tumor cells was examined by double staining of the cells with fluorescein (FITC) -annexin V analyzed by flow cytometry. RESULTS Optical imaging demonstrated distribution of PSVue 794 to both EG.7 and EL4 tumors at 1.5hr, but showed a high specific accumulation in EG.7 tumor, the target of OT-1 CD8 T cells, at 24hr and at later time points. Migration of the DDAO labeled OT-1 T cells to the EG.7 tumor was observed at the same site. Imaging of tumor sections revealed the co-localization of PSVue 794 and DDAO within EG.7 tumors. Flow cytometry analysis of cells isolated from the tumors demonstrated the binding of PSVue 794 to the dead EG.7 tumor cells, which were also stained with FITC-annexin V. Collectively, PSVue 794 visualized EG.7 tumor apoptosis induced by cytotoxic effect of OT-1 CD8 T cells targeted the tumor. CONCLUSION A near-infrared optical probe PSVue 794 with an apoptotic cell binding capacity enabled visualization of tumor cell death induced by cytotoxic T cells in vivo in an immune cell therapy model. This is a unique imaging method to monitor functionality and therapeutic effect of adoptively transferred T cells. CLINICAL RELEVANCE/APPLICATION Non-invasive in vivo imaging that allow us not only to track adoptively transferred cytotoxic T lymphocytes, but also to monitor the therapeutic effect, would contribute to the development and improve
    Radiological Society of North America 2011 Scientific Assembly and Annual Meeting; 11/2011
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    ABSTRACT: PURPOSE The aim of this study is to explore the feasibility of using Ferumoxytol, a Food and Drug Administration (FDA) approved ultrasmall superparamagnetic iron oxide (USPIO), for labeling and magnetic resonance imaging (MRI) of human natural killer (NK) cells. METHOD AND MATERIALS Human NK cells (CD3-/CD56+) isolated from PBMC and expanded in vitro were labeled with Ferumoxytol alone, Ferumoxytol with protamine sulfate (PS) or Ferumoxytol with PS and heparin (H) mixture. H was used to examine if it enhance the labeling. In each labeling condition, increasing concentrations of Ferumoxytol (equivalent to iron concentrations of 0–100 µg/mL) were used. The presence of USPIO in NK cells was confirmed by Prussian blue staining. The effects of the labeling on cell viability were examined by Trypan blue staining. To determine the MRI detection threshold of labeled NK cells in vitro, titration experiments with different numbers of labeled cells were performed using a clinical 3 T MRI system. RESULTS A labeling efficiency of >99% was achieved after incubating NK cells with 100 µg/mL of USPIO for 2 h either in the presence of PS (40µg/mL) or in the presence of the PS (40µg/mL)-H (2U/mL) mixture. No significant cell death was observed with either method. In vitro MRI of labeled NK cells revealed that both USPIO-PS and USPIO-PS-H mixture labeling methods resulted in a significant but similar signal intensity (SI) loss on T2*WI sequences (48% and 46%, respectively) (Figure1A). USPIO alone only showed minimum SI loss (5%) but no visible Prussian blue staining (Figure1B). While 10 6 cells/mL resulted in strong SI loss, as few as 105 cells/mL could also be detected in vitro relative to unlabeled cells by using this approach. CONCLUSION The results of this study indicate that: (1) human NK cells could be effectively labeled with either USPIO-PS or USPIO-PS-H mixtures. (2) Optimized NK cell labeling was achieved with a USPIO concentration of 100 µg/mL and an incubation time of 2 hr without posing significant adverse effects on the viability of cells; (3) While macrophages have been shown to take up USPIOs, to the best of our knowledge, this is the first study showing effective labeling of NK cells with USPIO. CLINICAL RELEVANCE/APPLICATION NK cells can be successfully labeled in vitro with an FDA approved USPIO and this method may enable imaging of innate immune responses and MRI-based tracking of human NK cells in patients with cancer.
    Radiological Society of North America 2011 Scientific Assembly and Annual Meeting; 11/2011
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    ABSTRACT: The ability of the unaided human eye to detect small cancer foci or accurate borders between cancer and normal tissue during surgery or endoscopy is limited. Fluorescent probes are useful for enhancing visualization of small tumors but are typically limited by either high background signal or the requirement for administration hours to days before use. We synthesized a rapidly activatable, cancer-selective fluorescence imaging probe, γ-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG), with intramolecular spirocyclic caging for complete quenching. Activation occurs by rapid one-step cleavage of glutamate with γ-glutamyltranspeptidase (GGT), which is not expressed in normal tissue, but is overexpressed on the cell membrane of various cancer cells, thus leading to complete uncaging and dequenching of the fluorescence probe. In vitro activation of gGlu-HMRG was evident in 11 human ovarian cancer cell lines tested. In vivo in mouse models of disseminated human peritoneal ovarian cancer, activation of gGlu-HMRG occurred within 1 min of topically spraying the tumor, creating high signal contrast between the tumor and the background. The gGlu-HMRG probe is practical for clinical application during surgical or endoscopic procedures because of its rapid and strong activation upon contact with GGT on the surface of cancer cells.
    Science translational medicine 11/2011; 3(110):110ra119. · 14.41 Impact Factor
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    ABSTRACT: Three major modes of cancer therapy (surgery, radiation and chemotherapy) are the mainstay of modern oncologic therapy. To minimize the side effects of these therapies, molecular-targeted cancer therapies, including armed antibody therapy, have been developed with limited success. In this study, we have developed a new type of molecular-targeted cancer therapy, photoimmunotherapy (PIT), that uses a target-specific photosensitizer based on a near-infrared (NIR) phthalocyanine dye, IR700, conjugated to monoclonal antibodies (mAbs) targeting epidermal growth factor receptors. Cell death was induced immediately after irradiating mAb-IR700-bound target cells with NIR light. We observed in vivo tumor shrinkage after irradiation with NIR light in target cells expressing the epidermal growth factor receptor. The mAb-IR700 conjugates were most effective when bound to the cell membrane and produced no phototoxicity when not bound, suggesting a different mechanism for PIT as compared to conventional photodynamic therapies. Target-selective PIT enables treatment of cancer based on mAb binding to the cell membrane.
    Nature medicine 11/2011; 17(12):1685-91. · 28.05 Impact Factor
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    ABSTRACT: Targeted therapies are designed to interfere with specific aberrant biologic pathways involved in tumor development. The main classes of novel oncologic drugs include antiangiogenic drugs, antivascular agents, drugs interfering with EGFR-HER2 or KIT receptors, inhibitors of the PI3K/Akt/mTOR pathway, and hormonal therapies. Cancer cells usurp normal signal transduction pathways used by growth factors to stimulate proliferation and sustain viability. The interaction of growth factors with their receptors activates different intracellular pathways affecting key tumor biologic processes such as neoangiogenesis, tumor metabolism, and tumor proliferation. The response of tumors to anticancer therapy can be evaluated with anatomic response assessment, qualitative response assessment, and response assessment with functional and molecular imaging. Angiogenesis can be measured by means of perfusion imaging with computed tomography and magnetic resonance (MR) imaging. Diffusion-weighted MR imaging allows imaging evaluation of tumor cellularity. The main imaging techniques for studying tumor metabolism in vivo are positron emission tomography and MR spectroscopy. Familiarity with imaging findings secondary to tumor response to targeted therapies may help the radiologist better assist the clinician in accurate evaluation of tumor response to these anticancer treatments. Functional and molecular imaging techniques may provide valuable data and augment conventional assessment of tumor response to targeted therapies. Supplemental material available at http://radiographics.rsna.org/lookup/suppl/doi:10.1148/rg.317115108/-/DC1.
    Radiographics 11/2011; 31(7):2059-91. · 2.73 Impact Factor
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    ABSTRACT: Pazopanib is an FDA approved Vascular Endothelial Growth Factor Receptor inhibitor. We previously reported that it also inhibits tumor cell B-Raf activity in an experimental brain metastatic setting. Here, we determine the effects of different B-Raf genotypes on pazopanib efficacy, in terms of primary tumor growth and anti-angiogenesis. A panel of seven human breast cancer and melanoma cell lines harboring different mutations in the Ras-Raf pathway was implanted orthotopically in mice, and tumor growth, ERK1/2, MEK1/2 and AKT activation, and blood vessel density and permeability were analyzed. Pazopanib was significantly inhibitory to xenografts expressing either exon 11 mutations of B-Raf, or HER2 activated wild type B-Raf; no significant inhibition of a xenograft expressing the common V600E B-Raf mutation was observed. Decreased pMEK staining in the responsive tumors confirmed that B-Raf was targeted by pazopanib. Interestingly, pazopanib inhibition of tumor cell B-Raf also correlated with its anti-angiogenic activity, as quantified by vessel density and area. In conclusion, using pazopanib, tumor B-Raf status was identified as a significant determinant of both tumor growth and angiogenesis.
    PLoS ONE 10/2011; 6(10):e25625. · 3.53 Impact Factor
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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. · 5.56 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. · 4.82 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

Publication Stats

18k Citations
2,711.56 Total Impact Points

Institutions

  • 2001–2014
    • NCI-Frederick
      • Laboratory of Pathology
      Maryland, United States
  • 1990–2014
    • National Institutes of Health
      • • Center for Cancer Research
      • • Branch of Radiation Oncology
      • • Center for Clinical Research
      Maryland, United States
  • 1970–2014
    • National Cancer Institute (USA)
      • • Molecular Imaging Program
      • • Laboratory of Pathology
      • • Genetic Epidemiology
      • • Surgery Branch
      Maryland, United States
  • 2013
    • The Jikei University School of Medicine
      • Department of Internal Medicine H
      Tokyo, Tokyo-to, Japan
  • 1998–2013
    • Leidos Biomedical Research
      Maryland, 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
    • Conselleria de Sanidade
      La Corogne, Galicia, Spain
    • United States Army
      Washington, West Virginia, United States
  • 2007–2011
    • The University of Tokyo
      • • Faculty & Graduate School of Medicine
      • • Faculty and Graduate School of Pharmaceutical Sciences
      Tokyo, Tokyo-to, Japan
    • Virginia State University
      Petersburg, Virginia, United States
    • Howard Hughes Medical Institute
      Ashburn, Virginia, United States
    • University of South Dakota
      Vermillion, South Dakota, United States
  • 2010
    • University of Copenhagen
      • Department of Clinical Biochemistry
      København, Capital Region, Denmark
    • Boston Children's Hospital
      Boston, Massachusetts, United States
  • 2006–2010
    • National Human Genome Research Institute
      Maryland, 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
      Maryland, 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, Pennsylvania, United States
  • 2002
    • National Institute of Allergy and Infectious Diseases
      Maryland, United States
    • National Eye Institute
      Maryland, United States
  • 2001–2002
    • George Mason University
      • Department of Computational and Data Sciences
      Fairfax, VA, United States
  • 1999–2002
    • GE India Industrial Pvt. Ltd.
      New Dilli, NCT, India
  • 1997
    • National Center for Genome Resources
      Santa Fe, New Mexico, United States
  • 1996
    • University of Alabama in Huntsville
      • Department of Computer Science
      Huntsville, Alabama, United States
  • 1992
    • The National Institute of Diabetes and Digestive and Kidney Diseases
      Maryland, United States