Cancer Targeted Technology (United States)

NetworldEurope, the European Technology Platform for Communications and Services, is one of the institutions that aims to address the challenges brought by this increased intertwining of ICT and society. In this context, NetworldEurope has built a Strategic Research<br> and Innovation Agenda (SRIA) for communications and services. We envision an establishment of a foundational basis for communications and services, on which other sectors can rely to plan their evolution and the deep transformational aspects that ICT will bring into the society at large. This technical annex is the second of two parts. The first one consists of a simplified, higher level vision of our technological roadmap, with an additional deep section providing simplified metrics tables that identifies reference specifications for technology at different times (referred as nodes) and expected technological features associated with those nodes. This second part is a companion document, providing technical details and providing a deeper reaching discussion on the technologies we envisage as key for the future, under the overall scope of ICT.

Background: Eptinezumab is approved in the US for the preventive treatment of migraine and was well tolerated in double-blind, placebo-controlled studies in patients with episodic and chronic migraine (CM). The PREVAIL study evaluated the long-term safety, immunogenicity, and impact on patient-reported outcomes of repeat doses of eptinezumab in patients with CM. Methods: PREVAIL was an open-label, phase 3 trial comprising two 48-week treatment phases. Adults with CM received eptinezumab 300 mg by 30-minute IV every 12 weeks for ≤8 doses, with patients followed up to week 104. Results: 128 adults (mean age, 41.5y) with CM were treated. Over 2 years, the most frequently reported treatment-emergent adverse events were nasopharyngitis (14.1%), upper respiratory tract infection (7.8%), sinusitis (7.8%), influenza (6.3%), bronchitis (5.5%), and migraine (5.5%). Study-drug discontinuation due to adverse events was 6.3%. Anti-eptinezumab antibody incidence peaked at week 24 and declined despite continued dosing, to nondetectable levels at week 104. Patient-reported outcomes were improved at first assessment (week 4) and generally sustained through week 104. Conclusions: In adults with CM, eptinezumab 300 mg demonstrated a favorable safety profile, limited long-term immunogenicity, early and sustained reductions in migraine-related burden, and improvements in health-related quality of life over 2 years.

This is a maintenance and bug fix release, with the addition of some minor features. Most relevant changes with respect to the former release are listed below: Improvements in Availability: Added the reading of reduced clock and ephemeris data (CED) in the Galileo E1B INAV message introduced in Galileo OS SIS ICD Issue 2.0. If the reduced CED is available before the full ephemeris set, it is used for PVT computation until the full set has not yet been received. This can contribute to shortening the Time-To-First-Fix. Still experimental. Added the exploitation of the FEC2 Erasure Correction in the Galileo E1B INAV message introduced in Galileo OS SIS ICD Issue 2.0. This can contribute to shortening the Time-To-First-Fix. Since the added computational cost could break some real-time configurations, this feature is disabled by default. Itcan be activated from the configuration file by adding <code>TelemetryDecoder_1B.enable_reed_solomon=true</code>. Reduction of the TTFF in GPS L1 and Galileo E1 by improving the frame synchronization mechanism. Improvements in Maintainability: The Contributor License Agreement (CLA) signing for new contributors has been replaced by a Developer's Certificate of Origin (DCO),which implies that contributed commits in a pull request need to be signed as a manifestation that contributors have the right to submit their work under the open source license indicated in the contributed file(s) (instead of asking them to sign the CLA document). Improved handling of changes in GNU Radio 3.9 FFT API. Improved handling of the filesystem library. Added an abstract class <code>SignalSourceInterface</code> and a common base class <code>SignalSourceBase</code>, which allow removing a lot of duplicated code in Signal Source blocks, and further abstract file-based interfaces behind them. Do not apply clang-tidy fixes to protobuf-generated headers. Refactored private implementation of flow graph connection and disconnection for improved source code readability. Added a base class for GNSS ephemeris, saving some duplicated code and providing a common nomenclature for ephemeris' parameters. New generated XML files make use of the new parameters' names. Update GSL implementation to 0.38.1. See https://github.com/gsl-lite/gsl-lite/releases/tag/v0.38.1 Update references to the latest GPS ICDs (IS-GPS-200M, IS-GPS-800H, IS-GPS-705H) published in May, 2021. Improvements in Portability: Avoid collision of the <code>cpu_features</code> library when installing the <code>volk_gnsssdr</code> library on its own, and VOLK has already installed its version. Added a new building option <code>ENABLE_OWN_CPUFEATURES</code>, defaulting to <code>ON</code> when building <code>gnss-sdr</code> but defaulting to <code>OFF</code> when building a stand-alone version of <code>volk_gnsssdr</code>. When this building option is set to <code>ON</code>, it forces the building of the local version of the <code>cpu_features</code> library, regardless of whether it is already installed or not. CMake's <code>&lt;policy_max&gt;</code> version bumped to 3.21. The minimum CMake version is 2.8.12. Fix building when using the Xcode generator, Xcode &gt;= 12 and CMake &gt;= 3.19. Fix building of FPGA blocks when linking against GNU Radio &gt;= 3.9 and/or Boost &gt;= 1.74. Fix linking of the <code>&lt;filesystem&gt;</code> library when using GCC 8.x and GNU Radio &gt;= 3.8. If the Matio library is not found, now it is configured and built by CMake instead of using autotools. Added support for Apple M1 AArch64 architecture processor and for FreeBSD on x86, improved AMD microarchitecture detection. CMake now selects the C++23 standard if the environment allows for it. Improved detection of Gnuplot and <code>gnss_sim</code> when cross-compiling. NEON kernel implementations of the <code>volk_gnsssdr</code> library are now enabled in aarch64 architectures. Improvements in Reliability Bug fix in the Galileo E1/E5 telemetry decoder that produced incorrect timing information if a satellite is lost and then readquired. Check satellites' health status. If a satellite is marked as not healthy in its navigation message, the corresponding observables are not used for navigation. Improvements in Usability: Added a new <code>Fifo_Signal_Source</code> implementation that allows using a Unix FIFO as a signal source, thus allowing to multiplex signal streams outside of <code>gnss-sdr</code>, letting another program hold access to the receiver, or allowing signal sources that are not supported by <code>gnss-sdr</code> but can dump the signal to a FIFO. Avoid segmentation faults in the flow graph connection and/or starting due to some common inconsistencies in the configuration file. Provide hints to the user in case of failed flow graph connection due to inconsistencies in the configuration file. Fix segmentation fault if the RINEX output was disabled. Added a feature that optionally enables the remote monitoring of GPS and Galileo ephemeris using UDP and Protocol Buffers. Now building the software passing the <code>-DENABLE_FPGA=ON</code> to CMake does not make the receiver unusable when running on non-FPGA-enabled platforms. On FPGA-enabled platforms, now it is possible to run non-FPGA-enabled configurations. Fix bug that made the Monitor block to always set to 0 the <code>carrier_phase_rads</code> parameter value. The <code>Labsat_Signal_Source</code> implementation of the <code>SignalSource</code> block now can read files in the LabSat 3 Wideband format (<code>.LS3W</code>). When using this format, this source block can provide multiple RF chain outputs. Replace <code>Receiver.sources_count</code> configuration parameter name by <code>GNSS-SDR.num_sources</code>. The former parameter name is still read to ensure backward compatibility with configuration files using that nomenclature. Fix bug in searching for gr-iio when CMake was re-run several times with different settings for the <code>-DENABLE_FMCOMMS2</code> or <code>-DENABLE_PLUTOSDR</code> building options. Fix building when using UHD &gt;= v4.0.0.0. Fix building for <code>-DENABLE_FMCOMMS2=ON</code> and/or <code>-DENABLE_PLUTOSDR=ON</code> when the built-in gr-iio module introduced in GNU Radio 3.10 is found. This in-tree GNU Radio module takes precedence over the gr-iio package provided at https://github.com/analogdevicesinc/gr-iio. If the GNU Radio module is found, the other one is ignored. File <code>changelog.md</code> renamed to the more usual <code>CHANGELOG.md</code> uppercase name. New global configuration parameter <code>GNSS-SDR.observable_interval_ms</code>, set by default to 20 [ms], allows to control the internal rate at which computed observables sets are processed (50 observables sets per second by default). Fix bug in the <code>Monitor.decimation_factor</code> parameter, which was not working properly for other values than 1. See the definitions of concepts and metrics at https://gnss-sdr.org/design-forces/

This paper analyzes the detection of a M-dimensional useful signal modeled as the output of a M xK MIMO filter driven by a K-dimensional white Gaussian noise, and corrupted by a M-dimensional Gaussian noise with mutually uncorrelated components. The study is focused on frequency domain test statistics based on the eigenvalues of an estimate of the spectral coherence matrix (SCM), obtained as a renormalization of the frequency-smoothed periodogram of the observed signal. If N denotes the sample size and B the smoothing span, it is proved that in the high-dimensional regime where M, B, N converge to infinity while K remains fixed, the SCM behaves as a certain correlated Wishart matrix. Exploiting well-known results on the behaviour of the eigenvalues of such matrices, it is deduced that the standard tests based on linear spectral statistics of the SCM fail to detect the presence of the useful signal in the high-dimensional regime. A new test based on the SCM, which is proved to be consistent, is also proposed, and its statistical performance is evaluated through numerical simulations.

Programmed cell death protein 1 (PD-1) is a crucial anticancer target, but the relatively low response rate and acquired resistance to existing antibody drugs highlight an urgent need to develop alternative targeting strategies. Here, we report the palmitoylation of PD-1, discover the main DHHC enzyme for this modification, reveal the mechanism of its effect on PD-1 protein stability, and rationally develop a peptide for targeting PD-1 expression. Palmitoylation promoted the trafficking of PD-1 to the recycling endosome, thus preventing its lysosome-dependent degradation. Palmitoylation of PD-1, but not of PD-L1, promoted mTOR signaling and tumor cell proliferation, and targeting palmitoylation displayed significant anti-tumor effects in a three-dimensional culture system. A peptide was designed to competitively inhibit PD-1 palmitoylation and expression, opening a new route for developing PD-1 inhibitors and combinatorial cancer immunotherapy.

&lt;p&gt;This release has several improvements in different dimensions, addition of new features and bug fixes:&lt;/p&gt; Improvements in Accuracy: &lt;ul&gt; &lt;li&gt;Part of the RTKLIB core library has been integrated into GNSS-SDR. There is now a single PVT block implementation which makes use of RTKLIB to deliver PVT solutions, including Single and PPP navigation modes.&lt;/li&gt; &lt;li&gt;Fixed CN0 estimation for other correlation times than 1 ms.&lt;/li&gt; &lt;li&gt;Improved computation of tracking parameters and GNSS observables.&lt;/li&gt; &lt;li&gt;Other minor bug fixes.&lt;/li&gt; &lt;/ul&gt; Improvements in Availability: &lt;ul&gt; &lt;li&gt;Internal Finite State Machines rewritten for improved continuity in delivering position fixes. This fixes a bug that was stalling the receiver after about six hours of continuous operation.&lt;/li&gt; &lt;li&gt;Redesign of the time counter for enhanced continuity.&lt;/li&gt; &lt;li&gt;Improved flow graph in multi-system configurations: the receiver does not get stalled anymore if no signal is found from the first system.&lt;/li&gt; &lt;li&gt;Improved acquisition and tracking sensitivity.&lt;/li&gt; &lt;li&gt;Added mechanisms for Assisted GNSS, thus shortening the Time-To-First-Fix. Provision of data via XML files or via SUPL v1.0. Documented at &lt;a href="https://gnss-sdr.org/docs/sp-blocks/global-parameters/"&gt;https://gnss-sdr.org/docs/sp-blocks/global-parameters/&lt;/a&gt;&lt;/li&gt; &lt;li&gt;Other minor bug fixes.&lt;/li&gt; &lt;/ul&gt; Improvements in Efficiency: &lt;ul&gt; &lt;li&gt;Added the possibility of non-blocking acquisition, which works well when using real-time data from an RF front-end.&lt;/li&gt; &lt;li&gt;Improved flow graph in multi-band configurations: satellites acquired in one band are immediately searched in others.&lt;/li&gt; &lt;li&gt;Complex local codes have been replaced by real codes, alleviating the computational burden.&lt;/li&gt; &lt;li&gt;New volk_gnsssdr kernels: volk_gnsssdr_16i_xn_resampler_16i_xn.h, volk_gnsssdr_16ic_16i_rotator_dot_prod_16ic_xn.h, volk_gnsssdr_32f_xn_resampler_32f_xn.h, volk_gnsssdr_32fc_32f_rotator_dot_prod_32fc_xn.h&lt;/li&gt; &lt;li&gt;Some AVX2 implementations added to the volk_gnsssdr library.&lt;/li&gt; &lt;li&gt;Improvement in C++ usage: Use of const container calls when result is immediately converted to a const iterator. Using these members removes an implicit conversion from iterator to const_iterator.&lt;/li&gt; &lt;li&gt;Output printers can be shut down, with some savings in memory and storage requirements.&lt;/li&gt; &lt;li&gt;A number of code optimizations here and there.&lt;/li&gt; &lt;/ul&gt; Improvements in Flexibility: &lt;ul&gt; &lt;li&gt;A number of new parameters have been exposed to the configuration system.&lt;/li&gt; &lt;li&gt;Possibility to choose Pilot or Data component for tracking of GPS L5 and Galileo E5a signals.&lt;/li&gt; &lt;li&gt;Enabled extended coherent integration times for signal tracking.&lt;/li&gt; &lt;li&gt;Configurable coherent and/or non-coherent signal acquisition.&lt;/li&gt; &lt;li&gt;Some configuration parameters can now be overridden by commandline flags for easier use in scripts.&lt;/li&gt; &lt;/ul&gt; Improvements in Interoperability: &lt;ul&gt; &lt;li&gt;Added the GPS L5 receiver chain.&lt;/li&gt; &lt;li&gt;Added the GLONASS L1 SP receiver chain.&lt;/li&gt; &lt;li&gt;Added the GLONASS L2 SP receiver chain.&lt;/li&gt; &lt;li&gt;Improvements in the Galileo E5a and GPS L2C receiver chains.&lt;/li&gt; &lt;li&gt;Updated list of available GNSS satellites.&lt;/li&gt; &lt;li&gt;Added five more signal sources: "Fmcomms2_Signal_Source" (requires gr-iio), "Plutosdr_Signal Source" (requires gr-iio), "Spir_GSS6450_File_Signal_Source", "Labsat_Signal_Source" and "Custom_UDP_Signal_Source" (requires libpcap). Documented in &lt;a href="https://gnss-sdr.org/docs/sp-blocks/signal-source/"&gt;https://gnss-sdr.org/docs/sp-blocks/signal-source/&lt;/a&gt;&lt;/li&gt; &lt;li&gt;Improved support for BladeRF, HackRF and RTL-SDR front-ends.&lt;/li&gt; &lt;li&gt;Added tools for the interaction with front-ends based on the AD9361 chipset.&lt;/li&gt; &lt;li&gt;Intermediate results are now saved in MAT-file format (.mat), readable from Matlab/Octave and from Python via h5py.&lt;/li&gt; &lt;li&gt;Added the GPX output format.&lt;/li&gt; &lt;li&gt;Improvements in the generation of KML files.&lt;/li&gt; &lt;li&gt;Improvements in the NMEA output. The receiver can produce GPGGA, GPRMC, GPGSA, GPGSV, GAGSA and GAGSV sentences.&lt;/li&gt; &lt;li&gt;Improvements in the RTCM server stability.&lt;/li&gt; &lt;li&gt;Improvements in the correctness of generated RINEX files.&lt;/li&gt; &lt;li&gt;The receiver can read and make use of Galileo almanac XML files published by the European GNSS Service Centre at &lt;a href="https://www.gsc-europa.eu/system-status/almanac-data"&gt;https://www.gsc-europa.eu/system-status/almanac-data&lt;/a&gt;&lt;/li&gt; &lt;li&gt;Own-defined XML schemas for navigation data published at &lt;a href="https://github.com/gnss-sdr/gnss-sdr/tree/next/docs/xml-schemas"&gt;https://github.com/gnss-sdr/gnss-sdr/tree/next/docs/xml-schemas&lt;/a&gt;&lt;/li&gt; &lt;li&gt;Added program rinex2assist to convert RINEX navigation files into XML files usable for Assisted GNSS. Only available building from source. See &lt;a href="https://github.com/gnss-sdr/gnss-sdr/tree/next/src/utils/rinex2assist"&gt;https://github.com/gnss-sdr/gnss-sdr/tree/next/src/utils/rinex2assist&lt;/a&gt;&lt;/li&gt; &lt;/ul&gt; Improvements in Maintainability: &lt;ul&gt; &lt;li&gt;Setup of a Continuous Integration system that checks building and runs QA code in a wide range of GNU/Linux distributions (Arch Linux, CentOS, Debian, Fedora, OpenSUSE, Ubuntu) and releases. See &lt;a href="https://gitlab.com/gnss-sdr/gnss-sdr"&gt;https://gitlab.com/gnss-sdr/gnss-sdr&lt;/a&gt;&lt;/li&gt; &lt;li&gt;Creation of multi-system processing blocks, drastically reducing code duplication and maintainability time.&lt;/li&gt; &lt;li&gt;Automated code formatting with clang-format. This tool is widely available and easy to integrate into many code editors, and it also can be used from the command line. It cuts time spent on adhering to the project's code formatting style.&lt;/li&gt; &lt;li&gt;Improvement in C++ usage: C-style casts have been replaced by C++ casts. C-style casts are difficult to search for. C++ casts provide compile time checking ability and express programmers' intent better, so they are safer and clearer.&lt;/li&gt; &lt;li&gt;Improvement in C++ usage: The override special identifier is now used when overriding a virtual function. This helps the compiler to check for type changes in the base class, making the detection of errors easier.&lt;/li&gt; &lt;li&gt;Improvement in C++ usage: A number of unused includes have been removed. Order of includes set to: local (in-source) headers, then library headers, then system headers. This helps to detect missing includes.&lt;/li&gt; &lt;li&gt;Improvement in C++ usage: Enhanced const correctness. Misuses of those variables are detected by the compiler.&lt;/li&gt; &lt;li&gt;Improved code with clang-tidy and generation of a compile_commands.json file containing the exact compiler calls for all translation units of the project in machine-readable form if clang-tidy is detected.&lt;/li&gt; &lt;li&gt;Applied some style rules to CMake scripts.&lt;/li&gt; &lt;li&gt;Minimal versions of dependencies identified and detected.&lt;/li&gt; &lt;/ul&gt; Improvements in Portability: &lt;ul&gt; &lt;li&gt;Several CMake scripts improvements, more verbose outputs in case of errors. Building configuration has been documented in &lt;a href="https://gnss-sdr.org/docs/tutorials/configuration-options-building-time/"&gt;https://gnss-sdr.org/docs/tutorials/configuration-options-building-time/&lt;/a&gt;&lt;/li&gt; &lt;li&gt;Improved SDK for cross-compilation in embedded devices. Documented in &lt;a href="https://gnss-sdr.org/docs/tutorials/cross-compiling/"&gt;https://gnss-sdr.org/docs/tutorials/cross-compiling/&lt;/a&gt;&lt;/li&gt; &lt;li&gt;Improved control over minimum required versions for core dependencies.&lt;/li&gt; &lt;li&gt;The software builds with C++11, C++14 and C++17 standards.&lt;/li&gt; &lt;li&gt;The software can now be built using GCC &gt;= 4.7.2 or LLVM/Clang &gt;= 3.4.0 compilers on GNU/Linux, and with Clang/AppleClang on MacOS.&lt;/li&gt; &lt;li&gt;The Ninja build system can be used in replacement of make.&lt;/li&gt; &lt;li&gt;The volk_gnsssdr library can be built using Python 2.7+ or Python 3.6+.&lt;/li&gt; &lt;li&gt;The volk_gnsssdr library is now ready for AArch64 NEON instructions.&lt;/li&gt; &lt;li&gt;Improved detection of required and optional dependencies in many GNU/Linux distributions and processor architectures.&lt;/li&gt; &lt;li&gt;Improvement in C++ usage: The &lt;ctime&gt; library has been replaced by the more modern and portable &lt;chrono&gt; (except for the interaction with RTKLIB).&lt;/li&gt; &lt;li&gt;Improvement in C++ usage: The &lt;stdio.h&gt; library has been replaced by the more modern and portable &lt;fstream&gt; for file handling.&lt;/li&gt; &lt;li&gt;Improvement in C++ usage: C++ libraries preferred over C libraries (e.g., &lt;cctype&gt; instead of &lt;ctype.h&gt;, &lt;cmath&gt; instead of &lt;math.h&gt;).&lt;/li&gt; &lt;li&gt;Fix compatibility with Boost 1.67 (closes Debian bug #911882 &lt;a href="https://bugs.debian.org/cgi-bin/bugreport.cgi?bug=911882"&gt;https://bugs.debian.org/cgi-bin/bugreport.cgi?bug=911882&lt;/a&gt;)&lt;/li&gt; &lt;li&gt;Fixes required by Debian packaging.&lt;/li&gt; &lt;li&gt;Fixes required by Macports packaging.&lt;/li&gt; &lt;li&gt;A downside in portability: BLAS and LAPACK libraries are now required even in ARM devices.&lt;/li&gt; &lt;li&gt;A downside in portability: the matio library &gt;= 1.5.3 is a new required dependency. If not found, it is downloaded and built automatically at building time, but this requires libtool, automake and h

e16562 Background: Urea-based 68Ga-PSMA PET is increasingly being utilized for diagnostic purposes in prostate cancer; however high tracer uptake within the salivary gland and kidney may be dose-limiting upon translation to radiotherapy. We developed a novel 18F labeled agent, CTT1057, a PSMA inhibitor based on a phosphoramidate scaffold with nanomolar and irreversible binding affinity to PSMA and robust internalization, and performed a first-in-human imaging study. Methods: Patients (pts) with metastatic castration resistant prostate cancer (mCRPC) were eligible. 10 mCi (370 MBq) of CTT1057 was injected and whole body PET/MR imaging (SIGNA PET/MR, GE) was performed 60 min post-injection. SUVmean in normal organs was recorded by drawing a 1 cm3 volume-of-interest. SUVmax was determined for each PSMA-avid metastasis. 10 randomly selected, consecutive 68Ga-PSMA PET scans from an independent cohort were used for descriptive comparison. Results: 5 pts with mCRPC were enrolled, with average age of 66 years (range 35–85) and median PSA of 12.2 (range 0.73 – 157.7). 55 PSMA-avid metastases were seen, including 37 osseous (average SUVmax = 8.1 ± 4.4), 15 lymph node (SUVmax = 11.0 ± 6.1), and 3 pulmonary (SUVmax = 3.2 ± 0.6). 31 (83%) and 12 (32%) of the PSMA-avid osseous lesions were visible on CT and bone scan, respectively. The mean short axis diameter of PSMA-avid lymph nodes was 0.7 ± 0.4 cm. Tumor-to-background ratios (liver, muscle, blood pool) were 2.8 ± 2.3, 14.9 ± 11.6, and 3.2 ± 2.4, respectively. SUVmean in salivary gland and kidney were 3.6 ± 0.4 and 9.1 ± 0.8 for CTT1057 and 15.8 ± 2.7 and 35.9 ± 9.6 for 68Ga-PSMA, respectively. No tracer-related adverse events were observed and radiation dose estimates for organs and whole-body effective dose were within acceptable limits. Conclusions: 18F-labeled CTT1057 targeting PSMA, detected mCRPC lesions in the soft tissue and bone at greater sensitivity than conventional imaging. CTT1057 distribution of uptake was similar to urea-based PSMA imaging, with preliminary evidence of lower uptake in the salivary gland and kidney. Further clinical studies of the CTT1057 backbone as a diagnostic and therapeutic agent in mCRPC are warranted. Clinical trial information: NCT02916537.

Keloids are fibroproliferative diseases characterized by the accumulation of an extracellular matrix including collagen. Various growth factors, or cytokines, and their receptors are overexpressed in keloids, and they are expected to be therapy targets. Sulforaphane, a dietary isothiocyanate, has recently shown anti-tumor, anti-inflammatory, and anti-fibrotic properties. In this study, we found that sulforaphane inhibited cell growth and reduced collagen at the mRNA and protein levels in keloid fibroblasts. Moreover, sulforaphane markedly suppressed the expression of IL-6 and α-SMA and inhibited Stat3 and Smad3 signaling pathways in keloid fibroblast KF112 cells. Sulforaphane induced G2/M cell-cycle arrest with the induction of p21 in KF112 cells. In addition, sulforaphane inhibited cell growth and suppressed the expression of collagen in keloid fibroblasts under a coculture with peripheral blood mononuclear cells. Furthermore, sulforaphane suppressed IL-6, Stat3, and Smad3 signaling in the coculture system. This study suggests that sulforaphane may be a novel keloid treatment.

A series of phosphoramidate-based prostate specific membrane antigen (PSMA) inhibitors of increasing lipophilicity were synthesized (4, 5, and 6), and their fluorine-18 analogs were evaluated for use as positron emission tomography (PET) imaging agents for prostate cancer. To gain insight into their modes of binding, they were also cocrystallized with the extracellular domain of PSMA. All analogs exhibited irreversible binding to PSMA with IC50 values ranging from 0.4 to 1.3 nM. In vitro assays showed binding and rapid internalization (80-95%, 2 h) of the radiolabeled ligands in PSMA(+) cells. In vivo distribution demonstrated significant uptake in CWR22Rv1 (PSMA(+)) tumor, with tumor to blood ratios of 25.6:1, 63.6:1, and 69.6:1 for [(18)F]4, [(18)F]5, and [(18)F]6, respectively, at 2 h postinjection. Installation of aminohexanoic acid (AH) linkers in the phosphoramidate scaffold improved their PSMA binding and inhibition and was critical for achieving suitable in vivo imaging properties, positioning [(18)F]5 and [(18)F]6 as favorable candidates for future prostate cancer imaging clinical trials.