11 research outputs found
Preparation and Characterization of Site-Specifically Radiolabeled 89Zr-DFO-anti-PD-L1-mAb ImmunoPET Tracer
Preparation and Characterization of Site-Specifically Radiolabeled 89Zr-DFO-anti-PD-L1-mAb ImmunoPET Tracer Feng-Yun J. Huanga,*, Ching-Chun Lua, Wei-Lin Lob, Shiou-Shiow Farnb, Chao-Wei Yangc aDepartment of Medical Imaging and Radiological Sciences, Central Taiwan University of Science and Technology: No.666, Buzih Road, Beitun District, Taichung City, 40605, Taiwan; bIsotope Division, Institute of Nuclear Energy Research: No.1000, Wenhua Road, Jiaan Village, Longtan District, Taoyuan City, 32546, Taiwan; cDepartment of Nuclear Medicine, Cheng Ching Hospital – Chung Kang Branch: No.966, Sec 4, Taiwan Blvd., Xitun Dist., Taichung City, 40764, Taiwan; *Corresponding Author Email Address: [email protected] Introduction Site-specifically radiolabeled immunoPET tracers have been demonstrated to provide superior imaging ability in vivo than conventional radiolabeled one (random method). In this study, preparation and characterization of site-specifically radiolabeled 89Zr-DFO-anti-PD-L1-mAb tracer will be investigated. The site-specific immunoPET tracer could detect the expression of immune checkpoint protein (ex. PD-L1/PD-1) on tumor for assessment of patient stratification before treatment and therapeutic efficacy after treatment. Description of the Work Materials & Methods: The technique of enzymatic glycan modification was utilized to prepare site-specifically radiolabeled 89Zr-immunoPET tracer. In brief, GlyCLICK® and SiteClick® kits were used to prepare azide-activated anti-PD-L1-mAb with degree of labeling of 2 and 4, respectively. Then bifunctional chelator DBCO-DFO was attached to the azide-functionalized antibodies via SPAAC click reaction to form site-specific DFO-anti-PD-L1-mAb conjugates with different chelator-to-antibody ratio (CAR) of 2 and 4. The quality control of conjugates were conducted and then radiolabeled with 89Zr in 1 M HEPES buffer, pH 7, and shaking with 300 rpm at RT for 40 min. In addition, in vitro stability of tracers was estimated in the PBS at RT after purification. Results: Both site-specific DFO-anti-PD-L1-mAb conjugates with CAR of 2 and 4 were performed as transparent, clear, without aggregation, chemical purity of 100%, pH of 7.0 – 7.5. Analysis of conjugates by LC-MS showed that CAR for GlyCLICK® and SiteClick® prepared DFO-anti-PD-L1-mAb conjugates was 2.04 and 3.62, respectively. Results from radio-TLC indicated that radiochemical purity of tracers with CAR of 2 and 4 reached 100% and 98.7%, respectively. In addition, the results from HPLC analysis revealed that radioimpurities in both tracers were less than 5%. For in vitro stability study, radiochemical purity of both tracers displayed no any decline until 7 d incubated in PBS at RT. Conclusions In this study, site-specifically radiolabeled 89Zr-DFO-anti-PD-L1-mAb tracer with CAR of 2 and 4 have been prepared and characterized. The LC-MS results demonstrate that CAR for GlyCLICK® and SiteClick® prepared DFO-anti-PD-L1-mAb conjugates was 2.04 and 3.62, respectively. Radiochemical purity of tracers with CAR of 2 and 4 were large than 98% and both of them showed excellent stability in vitro. Keywords: site-specifically radiolabeled; DFO; 89Zr; immunoPET; PD-L1/PD-1 References European Journal of Nuclear Medicine and Molecular Imaging, 2019;47(5):1302 – 1313
Preparation and Characterization of Site-Specifically Radiolabeled 89Zr-DFO-anti-PD-L1-mAb ImmunoPET Tracer
Preparation and Characterization of Site-Specifically Radiolabeled 89Zr-DFO-anti-PD-L1-mAb ImmunoPET Tracer Feng-Yun J. Huanga,*, Ching-Chun Lua, Wei-Lin Lob, Shiou-Shiow Farnb, Chao-Wei Yangc aDepartment of Medical Imaging and Radiological Sciences, Central Taiwan University of Science and Technology: No.666, Buzih Road, Beitun District, Taichung City, 40605, Taiwan; bIsotope Division, Institute of Nuclear Energy Research: No.1000, Wenhua Road, Jiaan Village, Longtan District, Taoyuan City, 32546, Taiwan; cDepartment of Nuclear Medicine, Cheng Ching Hospital – Chung Kang Branch: No.966, Sec 4, Taiwan Blvd., Xitun Dist., Taichung City, 40764, Taiwan; *Corresponding Author Email Address: [email protected] Introduction Site-specifically radiolabeled immunoPET tracers have been demonstrated to provide superior imaging ability in vivo than conventional radiolabeled one (random method). In this study, preparation and characterization of site-specifically radiolabeled 89Zr-DFO-anti-PD-L1-mAb tracer will be investigated. The site-specific immunoPET tracer could detect the expression of immune checkpoint protein (ex. PD-L1/PD-1) on tumor for assessment of patient stratification before treatment and therapeutic efficacy after treatment. Description of the Work Materials & Methods: The technique of enzymatic glycan modification was utilized to prepare site-specifically radiolabeled 89Zr-immunoPET tracer. In brief, GlyCLICK® and SiteClick® kits were used to prepare azide-activated anti-PD-L1-mAb with degree of labeling of 2 and 4, respectively. Then bifunctional chelator DBCO-DFO was attached to the azide-functionalized antibodies via SPAAC click reaction to form site-specific DFO-anti-PD-L1-mAb conjugates with different chelator-to-antibody ratio (CAR) of 2 and 4. The quality control of conjugates were conducted and then radiolabeled with 89Zr in 1 M HEPES buffer, pH 7, and shaking with 300 rpm at RT for 40 min. In addition, in vitro stability of tracers was estimated in the PBS at RT after purification. Results: Both site-specific DFO-anti-PD-L1-mAb conjugates with CAR of 2 and 4 were performed as transparent, clear, without aggregation, chemical purity of 100%, pH of 7.0 – 7.5. Analysis of conjugates by LC-MS showed that CAR for GlyCLICK® and SiteClick® prepared DFO-anti-PD-L1-mAb conjugates was 2.04 and 3.62, respectively. Results from radio-TLC indicated that radiochemical purity of tracers with CAR of 2 and 4 reached 100% and 98.7%, respectively. In addition, the results from HPLC analysis revealed that radioimpurities in both tracers were less than 5%. For in vitro stability study, radiochemical purity of both tracers displayed no any decline until 7 d incubated in PBS at RT. Conclusions In this study, site-specifically radiolabeled 89Zr-DFO-anti-PD-L1-mAb tracer with CAR of 2 and 4 have been prepared and characterized. The LC-MS results demonstrate that CAR for GlyCLICK® and SiteClick® prepared DFO-anti-PD-L1-mAb conjugates was 2.04 and 3.62, respectively. Radiochemical purity of tracers with CAR of 2 and 4 were large than 98% and both of them showed excellent stability in vitro. Keywords: site-specifically radiolabeled; DFO; 89Zr; immunoPET; PD-L1/PD-1 References European Journal of Nuclear Medicine and Molecular Imaging, 2019;47(5):1302 – 1313
quanteda/quanteda: CRAN v1.5.0
New features
<ul>
<li>Add <code>flatten</code> and <code>levels</code> arguments to <code>as.list.dictionary2()</code> to enable more flexible conversion of dictionary objects. (#1661)</li>
<li>In <code>corpus_sample()</code>, the <code>size</code> now works with the <code>by</code> argument, to control the size of units sampled from each group.</li>
<li>Improvements to <code>textstat_dist()</code> and <code>textstat_simil()</code>, see below.</li>
<li>Long tokens are not discarded automatically in the call to <code>tokens()</code>. (#1713)</li>
</ul>
Behaviour changes
<ul>
<li><code>textstat_dist()</code> and <code>textstat_simil()</code> now return sparse symmetric matrix objects using classes from the <strong>Matrix</strong> package. This replaces the former structure based on the <code>dist</code> class. Computation of these classes is now also based on the fast implementation in the <strong>proxyC</strong> package. When computing similarities, the new <code>min_simil</code> argument allows a user to ignore certain values below a specified similarity threshold. A new coercion method <code>as.data.frame.textstat_simildist()</code> now exists for converting these returns into a data.frame of pairwise comparisons. Existing methods such as <code>as.matrix()</code>, <code>as.dist()</code>, and <code>as.list()</code> work as they did before.</li>
<li>We have removed the "faith", "chi-squared", and "kullback" methods from <code>textstat_dist()</code> and <code>textstat_simil()</code> because these were either not symmetric or not invariant to document or feature ordering. Finally, the <code>selection</code> argument has been deprecated in favour of a new <code>y</code> argument. </li>
<li><code>textstat_readability()</code> now defaults to <code>measure = "Flesch"</code> if no measure is supplied. This makes it consistent with <code>textstat_lexdiv()</code> that also takes a default measure ("TTR") if none is supplied. (#1715)</li>
<li>The default values for <code>max_nchar</code> and <code>min_nchar</code> in <code>tokens_select()</code> are now NULL, meaning they are not applied if the user does not supply values. Fixes #1713.</li>
</ul>
Bug fixes and stability enhancements
<ul>
<li><code>kwic.corpus()</code> and <code>kwic.tokens()</code> behaviour now aligned, meaning that dictionaries are correctly faceted by key instead of by value. (#1684)</li>
<li>Improved formatting of <code>tokens()</code> verbose output. (#1683)</li>
<li>Subsetting and printing of subsetted kwic objects is more robust. (#1665)</li>
<li>The "Bormuth" and "DRP" measures are now fixed for <code>textstat_readability()</code>. (#1701)</li>
</ul>
quanteda/quanteda: CRAN v4.0.1
<p>Fixed:</p>
<ul>
<li><p>A failing test caused by the ever-shifting behaviour of <strong>Matrix</strong> and the devel R on r-devel-linux-x86_64-debian-clang and r-devel-linux-x86_64-debian-gcc.</p>
</li>
<li><p>An Undeclared package 'quanteda.textstats' in Rd xrefs.</p>
</li>
<li><p>An installation failure on r-devel-linux-x86_64-fedora-gcc due to searching for TBB in all the wrong places.</p>
</li>
</ul>
quanteda/quanteda: CRAN v4.0
<h1>quanteda 4.0.0</h1>
<h2>Changes and additions</h2>
<ul>
<li><p>Introduces the <code>tokens_xptr</code> objects that extend the <code>tokens</code> objects with external pointers for a greater efficiency. Once <code>tokens</code> objects are converted to <code>tokens_xptr</code> objects using <code>as.tokens_xptr()</code>, <code>tokens_*.tokens_xptr()</code> methods are called automatically.</p>
</li>
<li><p>Improved C++ functions to allow the users to change the number of threads for parallel computing in more flexible manner using <code>quanteda_options()</code>. The value of <code>threads</code> can be changed in the middle of analysis pipeline.</p>
</li>
<li><p>Makes <code>"word4"</code> the default (word) tokeniser, with improved efficiency, language handling, and customisation options.</p>
</li>
<li><p>Replaced all occurrences of the <strong>magrittr</strong> <code>%>%</code> pipe with the R pipe <code>|></code> introduced in R 4.1, although the <code>%>%</code> pipe is still re-exported and therefore available to all users of <strong>quanteda</strong> without loading any additional packages.</p>
</li>
<li><p>Added <code>min_ntoken</code> and <code>max_ntoken</code> to <code>tokens_subset()</code> and <code>dfm_subset()</code> to extract documents based on number of tokens easily. It is equivalent to selecting documents using <code>ntoken()</code>.</p>
</li>
<li><p>Added a new argument <code>apply_if</code> that allows a tokens-based operation to apply only to documents that meet a logical condition. This argument has been added to <code>tokens_select()</code>, <code>tokens_compound()</code>, <code>tokens_replace()</code>, <code>tokens_split()</code>, and <code>tokens_lookup()</code>. This is similar to applying <code>purrr::map_if()</code> to a tokens object, but is implemented within the function so that it can be performed efficiently in C++.</p>
</li>
<li><p>Added new arguments <code>append_key</code>, <code>separator</code> and <code>concatenator</code> to <code>tokens_lookup()</code>. These allow tokens matched by dictionary values to be retained with their keys appended to them, separated by <code>separator</code>. The addition of the <code>concatenator</code> argument allows additional control at the lookup stage for tokens that will be concatenated from having matched multi-word dictionary values. (#2324)</p>
</li>
<li><p>Added a new argument <code>remove_padding</code> to <code>ntoken()</code> and <code>ntype()</code> that allows for not counting padding that might have been left over from <code>tokens_remove(x, padding = TRUE</code>). This changes the previous number of types from <code>ntype()</code> when pads exist, by counting pads by default. (#2336)</p>
</li>
<li><p>Removed dependency on <strong>RcppParallel</strong> to improve the stability of the C++ code. This change requires the users of Linux-like OS to install the Intel TBB library manually to enable parallel computing.</p>
</li>
</ul>
<h2>Removals</h2>
<ul>
<li><p><code>bootstrap_dfm()</code> was removed for character and corpus objects. The correct way to bootstrap sentences is not to tokenize them as sentences and then bootstrap them from the dfm. This is consistent with requiring the user to tokenise objects prior to forming dfms or other "downstream" objects.</p>
</li>
<li><p><code>dfm()</code> no longer works on character or corpus objects, only on tokens or other dfm objects. This was deprecated in v3 and removed in v4.</p>
</li>
<li><p>Very old arguments to <code>dfm()</code> options that were not visible but worked with warnings (such as <code>stem = TRUE</code>) are removed.</p>
</li>
<li><p>Deprecated or renamed arguments formerly passed in <code>tokens()</code> that formerly mapped to the v3 arguments with a warning are removed.</p>
</li>
<li><p>Methods for <strong>readtext</strong> objects are removed, since these are data.frame objects that are straightforward to convert into a <code>corpus</code> object.</p>
</li>
<li><p><code>topfeatures()</code> no longer works on an fcm object. (#2141)</p>
</li>
</ul>
<h2>Deprecations</h2>
<ul>
<li><p>Some on-the-fly calculations applied to character or corpus objects that require a temporary tokenisation are now deprecated. This includes:</p>
<ul>
<li><code>nsentence()</code> -- use <code>lengths(tokens(x, what = "sentence"))</code> instead;</li>
<li><code>ntype()</code> -- use <code>ntype(tokens(x))</code> instead; and.</li>
<li><code>ntoken()</code> -- use <code>ntoken(tokens(x))</code> instead.</li>
<li><code>char_ngrams()</code> -- use <code>tokens_ngrams(tokens(x))</code> instead.</li>
</ul>
</li>
<li><p><code>corpus.kwic()</code> is deprecated, with the suggestion to form a corpus from using <code>tokens_select(x, window = ...)</code> instead.</p>
</li>
</ul>
quanteda/quanteda: CRAN v1.4.1
quanteda 1.4.1
Bug fixes and stability enhancements
<ul>
<li>Fixed an issue with special handling of whitespace variants that caused a test to fail when running Ubuntu 18.10 system with libicu-dev version 63.1 (#1604).</li>
<li>Fixed the operation of <code>docvars<-.corpus()</code> in a way that solves #1603 (reassignment of docvar names).</li>
</ul>
quanteda/quanteda: CRAN v4.0.2
<p>Minor fixes:</p>
<ul>
<li><p>A failing test caused by C++ code related to <code>fcm()</code> and how tokens objects are re-indexed.</p>
</li>
<li><p>An undeclared package 'quanteda.textstats' in Rd xrefs.</p>
</li>
</ul>
quanteda/quanteda: CRAN v3.2.2
Bug fixes and stability enhancements
fcm() computes the marginal frequency of upper-case tokens correctly (#2176).
tokens_chunk() keeps all the docid, including those of empty documents, in the original object.
tokens_select() recycles values when the length of startpos or endpos is less than ndoc(x).
tokens_lookup() and dfm_lookup() can apply very large dictionaries (more than 100,000 keys)
quanteda/quanteda: CRAN v2.1.1
Bug fixes and stability enhancements
corpus_reshape() now allows reshaping back to documents even when segmented texts were of zero length. (#1978)
Special handling applied for Solaris to some issues breaking on that build, relating to the caching in summary.corpus()/textstat_summary()
quanteda/quanteda: CRAN v4.3.0
Changes and additions
- Added corpus_chunk() for chunking texts into smaller documents.
- Significantly reduce the memory usage for the c operation on large tokens and tokens_xptr objects.
- Further improvements to the verbose messages for corpus, tokens, dfm and fcm objects.
- tokens_ngrams() now includes a new argument apply_if, functioning similar to this argument in tokens_compound() and tokens_lookup() (#2390).
- Replaced remove_unigram with match_pattern in object2id() to control the matching of single-word patterns or multi-word patterns.
- data_corpus_inaugural now updated for Trump 2025
