SPECT Imaging of Treatment-Related Tumor Necrosis Using Technetium-99m-Labeled Rhein

Purpose Noninvasive imaging of treatment-induced necrosis is important to distinguish early responders from patients resistant to the treatment plan, enabling the tailored-made therapeutic intervention. The purpose of this study was to explore the feasibility of [ 99m Tc]EDDA-HYNIC-2C-rhein for earl...

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Veröffentlicht in:Molecular imaging and biology 2019-08, Vol.21 (4), p.660-668
Hauptverfasser: Liang, Jiajia, Luo, Qi, Zhang, Dongjian, Jin, Qiaomei, Liu, Lichao, Liu, Wei, Gao, Meng, Zhang, Jian, Yin, Zhiqi
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container_end_page 668
container_issue 4
container_start_page 660
container_title Molecular imaging and biology
container_volume 21
creator Liang, Jiajia
Luo, Qi
Zhang, Dongjian
Jin, Qiaomei
Liu, Lichao
Liu, Wei
Gao, Meng
Zhang, Jian
Yin, Zhiqi
description Purpose Noninvasive imaging of treatment-induced necrosis is important to distinguish early responders from patients resistant to the treatment plan, enabling the tailored-made therapeutic intervention. The purpose of this study was to explore the feasibility of [ 99m Tc]EDDA-HYNIC-2C-rhein for early assessment of tumor response to treatment. Procedures In vitro necrosis avidity of [ 99m Tc]EDDA-HYNIC-2C-rhein was evaluated in human lung cancer A549 cells treated with hyperthermia. Single photon emission–computed tomography/X-ray-computed tomography (SPECT/CT) imaging was performed in rats bearing subcutaneous W256 tumor treated with combretastatin A-4 disodium phosphate (CA4P) and rats bearing orthotopic liver W256 tumor treated with a single microwave ablation. All rats were euthanized immediately after the imaging session for biodistribution and histology studies. The mechanism of necrosis avidity for the tracer was further explored by in vivo blocking experiment and in vitro histochemistry and fluorescence staining. Results The uptake of [ 99m Tc]EDDA-HYNIC-2C-rhein in necrotic cells was significantly higher than that in viable cells ( p  
doi_str_mv 10.1007/s11307-018-1285-9
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The purpose of this study was to explore the feasibility of [ 99m Tc]EDDA-HYNIC-2C-rhein for early assessment of tumor response to treatment. Procedures In vitro necrosis avidity of [ 99m Tc]EDDA-HYNIC-2C-rhein was evaluated in human lung cancer A549 cells treated with hyperthermia. Single photon emission–computed tomography/X-ray-computed tomography (SPECT/CT) imaging was performed in rats bearing subcutaneous W256 tumor treated with combretastatin A-4 disodium phosphate (CA4P) and rats bearing orthotopic liver W256 tumor treated with a single microwave ablation. All rats were euthanized immediately after the imaging session for biodistribution and histology studies. The mechanism of necrosis avidity for the tracer was further explored by in vivo blocking experiment and in vitro histochemistry and fluorescence staining. Results The uptake of [ 99m Tc]EDDA-HYNIC-2C-rhein in necrotic cells was significantly higher than that in viable cells ( p  &lt; 0.05). SPECT/CT imaging showed that an obvious “hot spot” was observed in the CA4P-treated tumor while not in the control tumor at 5 h after tracer injection. Ex vivo γ-counting revealed that the uptake of [ 99m Tc]EDDA-HYNIC-2C-rhein in tumor was increased 3.5-fold in rats treated with CA4P compared with rats treated with vehicle. Autoradiography and corresponding H&amp;E staining suggested that the higher overall radiotracer uptake in the treated tumors was attributed to the increased necrosis. Blocking with unlabeled HYNIC-2C-rhein demonstrated the specific binding of the radiotracer to necrotic tissues. The perfect match of autoradiograph and histochemistry staining and PI fluorescence staining revealed that necrosis avidity of the tracer may be attributable to intercalation with exposed DNA in necrotic tissues. Conclusion [ 99m Tc]EDDA-HYNIC-2C-rhein can image necrosis induced by anticancer therapy and holds potential for early assessment of treatment response.</description><identifier>ISSN: 1536-1632</identifier><identifier>EISSN: 1860-2002</identifier><identifier>DOI: 10.1007/s11307-018-1285-9</identifier><identifier>PMID: 30338432</identifier><language>eng</language><publisher>Cham: Springer International Publishing</publisher><subject>A549 Cells ; Ablation ; Animals ; Anthraquinones - chemistry ; Autoradiography ; Avidity ; Bearing ; Computation ; Computed tomography ; Deoxyribonucleic acid ; DNA ; Feasibility studies ; Fluorescence ; Gangrene ; Histochemistry ; Histology ; Humans ; Hyperthermia ; Imaging ; Liver ; Lung cancer ; Lung Neoplasms - diagnostic imaging ; Lung Neoplasms - pathology ; Medical imaging ; Medicine ; Medicine &amp; Public Health ; Necrosis ; Photon emission ; Radioactive tracers ; Radiology ; Rats ; Rats, Sprague-Dawley ; Research Article ; Single photon emission computed tomography ; Sodium hydrogen phosphate ; Sodium phosphate ; Staining ; Technetium ; Technetium - chemistry ; Technetium isotopes ; Tissue Distribution ; Tissues ; Tomography ; Tomography, Emission-Computed, Single-Photon ; Tomography, X-Ray Computed ; Tumors</subject><ispartof>Molecular imaging and biology, 2019-08, Vol.21 (4), p.660-668</ispartof><rights>World Molecular Imaging Society 2018</rights><rights>Molecular Imaging and Biology is a copyright of Springer, (2018). All Rights Reserved.</rights><rights>Copyright Springer Nature B.V. 2019</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c400t-e305fdadc80f64a843353493ddba13fc015996759f9fcc62fde41fac868dd86f3</citedby><cites>FETCH-LOGICAL-c400t-e305fdadc80f64a843353493ddba13fc015996759f9fcc62fde41fac868dd86f3</cites><orcidid>0000-0002-8402-9753</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s11307-018-1285-9$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11307-018-1285-9$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30338432$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liang, Jiajia</creatorcontrib><creatorcontrib>Luo, Qi</creatorcontrib><creatorcontrib>Zhang, Dongjian</creatorcontrib><creatorcontrib>Jin, Qiaomei</creatorcontrib><creatorcontrib>Liu, Lichao</creatorcontrib><creatorcontrib>Liu, Wei</creatorcontrib><creatorcontrib>Gao, Meng</creatorcontrib><creatorcontrib>Zhang, Jian</creatorcontrib><creatorcontrib>Yin, Zhiqi</creatorcontrib><title>SPECT Imaging of Treatment-Related Tumor Necrosis Using Technetium-99m-Labeled Rhein</title><title>Molecular imaging and biology</title><addtitle>Mol Imaging Biol</addtitle><addtitle>Mol Imaging Biol</addtitle><description>Purpose Noninvasive imaging of treatment-induced necrosis is important to distinguish early responders from patients resistant to the treatment plan, enabling the tailored-made therapeutic intervention. The purpose of this study was to explore the feasibility of [ 99m Tc]EDDA-HYNIC-2C-rhein for early assessment of tumor response to treatment. Procedures In vitro necrosis avidity of [ 99m Tc]EDDA-HYNIC-2C-rhein was evaluated in human lung cancer A549 cells treated with hyperthermia. Single photon emission–computed tomography/X-ray-computed tomography (SPECT/CT) imaging was performed in rats bearing subcutaneous W256 tumor treated with combretastatin A-4 disodium phosphate (CA4P) and rats bearing orthotopic liver W256 tumor treated with a single microwave ablation. All rats were euthanized immediately after the imaging session for biodistribution and histology studies. The mechanism of necrosis avidity for the tracer was further explored by in vivo blocking experiment and in vitro histochemistry and fluorescence staining. Results The uptake of [ 99m Tc]EDDA-HYNIC-2C-rhein in necrotic cells was significantly higher than that in viable cells ( p  &lt; 0.05). SPECT/CT imaging showed that an obvious “hot spot” was observed in the CA4P-treated tumor while not in the control tumor at 5 h after tracer injection. Ex vivo γ-counting revealed that the uptake of [ 99m Tc]EDDA-HYNIC-2C-rhein in tumor was increased 3.5-fold in rats treated with CA4P compared with rats treated with vehicle. Autoradiography and corresponding H&amp;E staining suggested that the higher overall radiotracer uptake in the treated tumors was attributed to the increased necrosis. Blocking with unlabeled HYNIC-2C-rhein demonstrated the specific binding of the radiotracer to necrotic tissues. The perfect match of autoradiograph and histochemistry staining and PI fluorescence staining revealed that necrosis avidity of the tracer may be attributable to intercalation with exposed DNA in necrotic tissues. 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The purpose of this study was to explore the feasibility of [ 99m Tc]EDDA-HYNIC-2C-rhein for early assessment of tumor response to treatment. Procedures In vitro necrosis avidity of [ 99m Tc]EDDA-HYNIC-2C-rhein was evaluated in human lung cancer A549 cells treated with hyperthermia. Single photon emission–computed tomography/X-ray-computed tomography (SPECT/CT) imaging was performed in rats bearing subcutaneous W256 tumor treated with combretastatin A-4 disodium phosphate (CA4P) and rats bearing orthotopic liver W256 tumor treated with a single microwave ablation. All rats were euthanized immediately after the imaging session for biodistribution and histology studies. The mechanism of necrosis avidity for the tracer was further explored by in vivo blocking experiment and in vitro histochemistry and fluorescence staining. Results The uptake of [ 99m Tc]EDDA-HYNIC-2C-rhein in necrotic cells was significantly higher than that in viable cells ( p  &lt; 0.05). SPECT/CT imaging showed that an obvious “hot spot” was observed in the CA4P-treated tumor while not in the control tumor at 5 h after tracer injection. Ex vivo γ-counting revealed that the uptake of [ 99m Tc]EDDA-HYNIC-2C-rhein in tumor was increased 3.5-fold in rats treated with CA4P compared with rats treated with vehicle. Autoradiography and corresponding H&amp;E staining suggested that the higher overall radiotracer uptake in the treated tumors was attributed to the increased necrosis. Blocking with unlabeled HYNIC-2C-rhein demonstrated the specific binding of the radiotracer to necrotic tissues. The perfect match of autoradiograph and histochemistry staining and PI fluorescence staining revealed that necrosis avidity of the tracer may be attributable to intercalation with exposed DNA in necrotic tissues. Conclusion [ 99m Tc]EDDA-HYNIC-2C-rhein can image necrosis induced by anticancer therapy and holds potential for early assessment of treatment response.</abstract><cop>Cham</cop><pub>Springer International Publishing</pub><pmid>30338432</pmid><doi>10.1007/s11307-018-1285-9</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-8402-9753</orcidid></addata></record>
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subjects A549 Cells
Ablation
Animals
Anthraquinones - chemistry
Autoradiography
Avidity
Bearing
Computation
Computed tomography
Deoxyribonucleic acid
DNA
Feasibility studies
Fluorescence
Gangrene
Histochemistry
Histology
Humans
Hyperthermia
Imaging
Liver
Lung cancer
Lung Neoplasms - diagnostic imaging
Lung Neoplasms - pathology
Medical imaging
Medicine
Medicine & Public Health
Necrosis
Photon emission
Radioactive tracers
Radiology
Rats
Rats, Sprague-Dawley
Research Article
Single photon emission computed tomography
Sodium hydrogen phosphate
Sodium phosphate
Staining
Technetium
Technetium - chemistry
Technetium isotopes
Tissue Distribution
Tissues
Tomography
Tomography, Emission-Computed, Single-Photon
Tomography, X-Ray Computed
Tumors
title SPECT Imaging of Treatment-Related Tumor Necrosis Using Technetium-99m-Labeled Rhein
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