Cancer biotherapy & radiopharmaceuticals最新文献

{"title":"Distribution Characteristics of Colorectal Peritoneal Carcinomatosis Based on the Positron Emission Tomography/Peritoneal Cancer Index.","authors":"Chun-Feng Sun,&nbsp;Zhong-Hua Tan,&nbsp;Chen Shen,&nbsp;Xiao-Ying Mao,&nbsp;Cheng-Chun Ge,&nbsp;Yan Gao,&nbsp;Chun-Hong Hu","doi":"10.1089/cbr.2020.3733","DOIUrl":"https://doi.org/10.1089/cbr.2020.3733","url":null,"abstract":"<p><p><b><i>Background:</i></b> Colorectal peritoneal carcinomatosis (CRPC) is a primary cause of death in colorectal cancer (CRC) patients. In the past, computed tomography (CT) has been the primary method used to evaluate the distribution of CRPC. This study uses ¹⁸F-FDG positron emission tomography/computed tomography (PET/CT) to investigate the distribution characteristics of CRPC. <b><i>Materials and Methods:</i></b> The distribution characteristics of 46 patients with CRC who were treated in the authors' hospital were retrospectively analyzed using the peritoneal cancer index (PCI). <b><i>Results:</i></b> The 46 patients in the study showed CRPC involvement in 203 of the 598 abdominal and pelvic regions studied (33.9%, 203/598). The regional proportions of CRPC involvement, from high to low, were as follows: region 6 (13.8%), region 0 (10.3%), region 1 (9.9%), region 5 (8.9%), region 7 (8.4%), region 3 (8.4%), region 2 (7.4%), region 4 (7.4%), region 11 (6.9%), region 8 (6.4%), region 12 (5.4%), region 9 (3.4%), and region 10 (3.4%). Thirty-three patients had a PCI of <20, and 13 patients had a PCI of ≥20. Those 13 were among the 17 (37% 17/46) who had CRPC involvement in all three regions. According to the location of the primary CRC focus, the 46 patients were divided into three groups: right hemicolon, left hemicolon, and rectum. The frequency of CRPC was greater in the rectum group than in the left hemicolon group, and the SUV_max of CRPC was greater in the right hemicolon group than in the left hemicolon group; these differences were statistically significant (<i>p</i> < 0.05). <b><i>Conclusions:</i></b> The distribution of CRPC has certain characteristics in the abdominal and pelvic cavities. The PET-PCI scores can provide a basis for the diagnosis and clinical treatment strategies in patients with CRC.</p>","PeriodicalId":518937,"journal":{"name":"Cancer biotherapy & radiopharmaceuticals","volume":" ","pages":"517-526"},"PeriodicalIF":3.4,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.2020.3733","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38294470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epidermal Growth Factor Receptor Mutation Mechanisms in Nonsmall Cell Lung Cancer by Transcriptome Sequencing.","authors":"Min Yu,&nbsp;Shufen Huo,&nbsp;Li Sun,&nbsp;Jinglong Gao,&nbsp;Yi Liu,&nbsp;Jiao Yu,&nbsp;Fuqiang Liu,&nbsp;Sen Sheng,&nbsp;Xinyu Nie,&nbsp;Qiaofeng Nan,&nbsp;Yingxuan Tian","doi":"10.1089/cbr.2020.4049","DOIUrl":"https://doi.org/10.1089/cbr.2020.4049","url":null,"abstract":"<p><p><b><i>Background:</i></b> This study intended to investigate the mechanisms underlying the epidermal growth factor receptor (EGFR) mutations in nonsmall cell lung cancer (NSCLC). <b><i>Materials and Methods:</i></b> Lung cancer tissue samples were collected from 20 patients with NSCLC (6 EGFR mutation types assigned into 2 categories and 14 EGFR wild types assigned to 4 categories). The samples were subjected to transcriptome sequencing, followed by identification of the differentially expressed mRNAs (DEMs), differentially expressed lncRNAs (DELs), and differentially expressed circRNAs (DECs) between the mutation and nonmutation groups. Function analysis and microRNA (miRNA) prediction for DEMs were performed. The correlations between long noncoding RNA (lncRNA)/circular RNA (circRNA) and messenger RNA (mRNA) were analyzed. In addition, the targeting lncRNA and circRNA of miRNA were predicted. Finally, competing endogenous RNA (ceRNA) network was constructed, and survival analysis for the mRNAs involved in the network was performed. <b><i>Results:</i></b> In total, 323 DEMs, 284 DELs, and 224 DECs were identified between EGFR mutation and nonmutation groups. The DEMs were significantly involved in gene ontology functions related to cilium morphogenesis and assembly. ceRNA networks were constructed based on the DEMs, DELs, DECs, and predicted miRNAs. Survival analysis showed that four genes in the ceRNA network, including <i>ABCA3</i>, <i>ATL2</i>, <i>VAMP1</i>, and <i>APLN</i>, were significantly associated with prognosis. The four genes were involved in several ceRNA pathways, including RP1-191J18/circ_000373/miR-520a-5p/<i>ABCA3</i>, RP5-1014D13/let-7i-5p/<i>ATL2</i>, circ_000373/miR-1293/<i>VAMP1</i>, and RP1-191J18/circ_000373/miR-378a-5p/<i>APLN</i>. <b><i>Conclusion:</i></b> EGFR mutations in NSCLC may be associated with cilium dysfunction and complex ceRNA regulatory mechanisms. The key RNAs in the ceRNA network may be used as promising biomarkers for predicting EGFR mutations in NSCLC.</p>","PeriodicalId":518937,"journal":{"name":"Cancer biotherapy & radiopharmaceuticals","volume":" ","pages":"560-568"},"PeriodicalIF":3.4,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38915262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pinocembrin Inhibits the Proliferation, Migration, Invasiveness, and Epithelial-Mesenchymal Transition of Colorectal Cancer Cells by Regulating LACTB.","authors":"Lai Jiang,&nbsp;Yongbo Yang,&nbsp;Haiyang Feng,&nbsp;Qinfei Zhou,&nbsp;Yong Liu","doi":"10.1089/cbr.2020.4052","DOIUrl":"https://doi.org/10.1089/cbr.2020.4052","url":null,"abstract":"<p><p><b><i>Background:</i></b> Colorectal cancer (CRC) is a common malignancy of digestive tract. Pinocembrin (PINO) has been discovered to have a proapoptotic effect on CRC. This study aimed to elucidate how other biological behaviors of CRC cells were affected under PINO treatment. <b><i>Materials and Methods:</i></b> The effect of PINO on HT29 and HCT116 cells were detected through treatment of different concentrations of PINO. The role of LACTB in PINO treatment was investigated by transfection of siRNA-LACTB. Cell counting kit-8 assay, wound healing assay, and Transwell assay were conducted to evaluate the proliferation, migration, and invasiveness of CRC cells, respectively. Western blot or quantitative reverse transcription-polymerase chain reaction was carried out to measure the expressions of LACTB, matrix metalloproteinase (MMP)-2, E-cadherin, and N-cadherin. <b><i>Results:</i></b> Gradient PINO inhibited the viability, migration, invasiveness, and expressions of MMP-2 and N-cadherin in CRC cells, while promoted E-cadherin and LACTB expressions. Silencing LACTB promoted the viability, migration, invasiveness, and expressions of MMP-2 and N-cadherin in CRC cells and inhibited E-cadherin expression. PINO counteracted the effect of silenced LACTB, and yet silencing LACTB partially abolished the effect of PINO on CRC cells. <b><i>Conclusion:</i></b> PINO inhibited the proliferation, migration, invasiveness, and epithelial-to-mesenchymal transition of CRC cells by regulating LACTB.</p>","PeriodicalId":518937,"journal":{"name":"Cancer biotherapy & radiopharmaceuticals","volume":" ","pages":"527-536"},"PeriodicalIF":3.4,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39114220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Expression of Concern re</i>: Exosome-Mediated Transfer of Long Noncoding RNA HOTAIR Regulates Temozolomide Resistance by miR-519a-3p/RRM1 Axis in Glioblastoma (doi: 10.1089/cbr.2019.3499).","authors":"","doi":"10.1089/cbr.2019.3499.expcon","DOIUrl":"https://doi.org/10.1089/cbr.2019.3499.expcon","url":null,"abstract":"","PeriodicalId":518937,"journal":{"name":"Cancer biotherapy & radiopharmaceuticals","volume":" ","pages":"515"},"PeriodicalIF":3.4,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40677796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic Mechanism of Leukemia Relapse Following CD19 Chimeric Antigen Receptor T Cell Therapy.","authors":"Songlin Qiu,&nbsp;Ye Pan,&nbsp;Shenyan Shi,&nbsp;Fapohunda Funmilayo Omotoyosi,&nbsp;Keping Chen,&nbsp;Zhigang Guo,&nbsp;Peng Lü","doi":"10.1089/cbr.2020.4630","DOIUrl":"https://doi.org/10.1089/cbr.2020.4630","url":null,"abstract":"<p><p>Chimeric antigen receptor T cell therapy (CART) has achieved excellent results in the past 10 years for treating of leukemia. Treatment of B cell acute lymphoblastic leukemia by anti-CD19 CART can reach a complete remission rate of 90%. Although CART has greatly improved the treatment of patients with leukemia and lymphoma, as many as one-third of the patients can suffer disease relapse after CART. The tumor surface marker CD19 is negative in most the patients who relapse, and these patients display high expression of CD19 before treatment. In this review, the current causes of CD19-negative relapses after CD19 CART against leukemia, and the mechanisms of target escape are briefly summarized. Also, methods and strategies for treating relapse to provide references for the treatment of leukemia relapse are also discussed.</p>","PeriodicalId":518937,"journal":{"name":"Cancer biotherapy & radiopharmaceuticals","volume":" ","pages":"335-341"},"PeriodicalIF":3.4,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25495041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis, Radiolabeling, and Preclinical Evaluation of ⁶⁸Ga/¹⁷⁷Lu-Labeled Leuprolide Peptide Analog for the Detection of Breast Cancer.","authors":"Subhani M Okarvi,&nbsp;Ibrahim Al-Jammaz","doi":"10.1089/cbr.2021.0370","DOIUrl":"https://doi.org/10.1089/cbr.2021.0370","url":null,"abstract":"<p><p><b><i>Objectives:</i></b> The expansion of novel and potent tumor receptor binding peptides is a promising approach for the precise targeting of various cancer. Leuprolide is a 9-residue peptide analog of gonadotropin-releasing hormone and is extensively used in the treatment of sex hormone-dependent tumors, including prostate, breast, and ovarian cancer. This preclinical study was undertaken to prepare a new radiolabeled leuprolide peptide for the detection of breast carcinoma. <b><i>Methods:</i></b> A 1,4,7,10-tetraazacyclododecane-<i>N,N</i>'<i>,N</i>''<i>,N</i>'''-tetraacetic acid (DOTA)-coupled 9-amino acid leuprolide peptide was synthesized after typical 9-fluorenylmethyl-oxycarbonyl-based solid-phase peptide synthesis and radiolabeled with both ⁶⁸Ga and ¹⁷⁷Lu radionuclides for theranostic use. The systemic pharmacokinetics was done in healthy balb/c mice. The <i>in vitro</i> tumor cell binding affinity was determined on MCF7, T47D, and MDA-MB-231 breast cancer cell lines. <i>In vivo</i> tumor targeting and micro positron-emission tomography imaging was performed on nude mice with MCF7 breast tumor xenografts. <b><i>Results:</i></b> The leuprolide peptide was conveniently synthesized by solid-phase synthesis strategy and its identity and purity were validated by mass spectrometry and high-performance liquid chromatography. The peptide radiolabeled efficiently (˃94%) with both diagnostic (⁶⁸Ga) and therapeutic (¹⁷⁷Lu) radionuclides and displayed nanomolar binding potency to all three tested MCF7, T47D, and MDA-MB-231 cell lines. Fast and favorable pharmacokinetics was observed for ⁶⁸Ga/¹⁷⁷Lu-leuprolide in healthy Balb/c mice. In nude mice, ⁶⁸Ga-leuprolide peptide exhibited rapid clearance from the blood circulation with low to moderate (up to 5% ID/g) uptake/retention by the major body organs. The accumulation in the estrogen receptor-positive MCF7 tumor was 2.24% ± 0.62% ID/g at 45 min p.i, with good tumor to blood and muscle uptake ratios. The radiolabeled peptide was excreted primarily through the renal pathway. <b><i>Conclusion:</i></b> The encouraging results of this initial study demonstrate that additional testing of this leuprolide peptide seems to be indicated because of its convincing potential to be a new agent for the management of breast carcinoma.</p>","PeriodicalId":518937,"journal":{"name":"Cancer biotherapy & radiopharmaceuticals","volume":" ","pages":"372-383"},"PeriodicalIF":3.4,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40320898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fluoroscopy-Guided Salvage Photodynamic Therapy Combined with Nanoparticle Albumin-Bound Paclitaxel for Locally Advanced Esophageal Cancer after Chemoradiotherapy: A Case Report and Literature Review.","authors":"Wenhao Zhao,&nbsp;Jing Zhao,&nbsp;Lin Kang,&nbsp;Chen Li,&nbsp;Zhenning Xu,&nbsp;Jing Li,&nbsp;Ming Zhang","doi":"10.1089/cbr.2020.4595","DOIUrl":"https://doi.org/10.1089/cbr.2020.4595","url":null,"abstract":"<p><p><b><i>Background:</i></b> Among total cancer deaths, esophageal cancer ranks sixth in mortality. Radiotherapy and chemotherapy remain the main treatments for unresectable, locally advanced esophageal cancer, but a relapse and drug resistance are still common. The optimized choice for therapeutic schemes with low toxicity and a high quality of life is unclear when local progression occurs after radiotherapy and chemotherapy. Fluoroscopy-guided photodynamic therapy (PDT) on patients with recurrent esophageal cancer in whom the endoscope cannot pass may be used as a salvage treatment, and nanoparticle albumin-bound paclitaxel (Nab-P) has been shown to be effective for advanced esophageal cancer. The combination of PDT and Nab-P might be an effective and tolerable option for advanced esophageal cancer. <b><i>Case summary:</i></b> The authors present a 65-year-old male patient diagnosed with esophageal squamous cell carcinoma (ESCC) confirmed to have developed local progression after receiving radiotherapy and chemotherapy. Severe esophageal stenosis, mild malnutrition and anemia, and radiation pneumonia were found when he was admitted to the authors' hospital. For rapid reduction of tumor burden and to restore normal diet, he received PDT by the X-ray fluoroscopy positioning method and Nab-P chemotherapy. The patient obtained clinical benefit from these treatments, and improved his quality of life. <b><i>Conclusions:</i></b> This case demonstrates potential advantages of fluoroscopy-guided PDT combined with Nab-P in reducing the tumor load, preserving organ function, and improving the quality of life, as well as the beneficial effect on locally advanced esophageal cancer after radiotherapy and chemotherapy. This combination therapy provides an alternative for the clinical treatment of locally advanced esophageal cancer and it has broad prospects in treatment of the disease. <b><i>Core tip:</i></b> Herein, the authors report a case of a patient with ESCC who suffered locally progressive disease after chemotherapy and radiotherapy as well as malnutrition and mild anemia because of feeding difficulties. The patient was treated with PDT, which was assisted by a new positioning technique of X-ray fluoroscopy and Nab-P chemotherapy, and finally achieved clinical benefits. In addition, a modified transnasal feeding tube was also applied in the process of fluoroscopy-guided PDT in this article.</p>","PeriodicalId":518937,"journal":{"name":"Cancer biotherapy & radiopharmaceuticals","volume":" ","pages":"410-416"},"PeriodicalIF":3.4,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25539020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Facile Strategy for Preparation of Yttrium-90 Therapeutic Sources for Radionuclide Therapy.","authors":"Archana Mukherjee,&nbsp;Usha Pandey,&nbsp;Samina H Shaikh,&nbsp;Manoj Kumar,&nbsp;Vivek Kaushik,&nbsp;Poonam Jagasia,&nbsp;Sanjukta A Kumar,&nbsp;Prem Singh Dhami","doi":"10.1089/cbr.2021.0347","DOIUrl":"https://doi.org/10.1089/cbr.2021.0347","url":null,"abstract":"<p><p><b><i>Background:</i></b> Mold brachytherapy using high-energy <i>β</i>^--emitting radioisotopes is a promising treatment modality for skin cancers and keloids. Simple methodologies for consistent and stable incorporation of radionuclides into the matrix are desired for preparation of therapeutic sources. <b><i>Methods:</i></b> The authors report a facile strategy for the stable incorporation of Yttrium-90 (⁹⁰Y) into amidoxime-functionalized polyacrylonitrile-polyvinylidene fluoride (PAN-PVDF) membranes. The strategy consisted of surface modification of PAN-PVDF membranes by reaction with hydroxylamine, characterization of the functionalized membranes, and optimization of experimental variables for maximum loading of ⁹⁰Y onto the membranes. Quality control tests essential for confirming the suitability of the ⁹⁰Y therapeutic sources for human application, such as uniformity of activity distribution, absence of leaching of activity, and estimation of surface contamination, were performed. Theoretical calculations to estimate the dose imparted by the ⁹⁰Y therapeutic sources at varying depths of tissue were also carried out to predict the possible therapeutic outcome of treatment. <b><i>Results:</i></b> A facile method for large-scale preparation of ⁹⁰Y-based mold brachytherapy sources could be established. <b><i>Conclusions:</i></b> The source fabrication methodology standardized in this work could be tailored for fabrication of custom-made ⁹⁰Y sources for individualized treatment of superficial tumors, Bowen's disease, and keloids.</p>","PeriodicalId":518937,"journal":{"name":"Cancer biotherapy & radiopharmaceuticals","volume":" ","pages":"364-371"},"PeriodicalIF":3.4,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39947120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Pilot Study of Hepatic Irradiation with Yttrium-90 Microspheres Followed by Immunotherapy with Ipilimumab and Nivolumab for Metastatic Uveal Melanoma.","authors":"David R Minor,&nbsp;Kevin B Kim,&nbsp;Ricky T Tong,&nbsp;Max C Wu,&nbsp;Mohammed Kashani-Sabet,&nbsp;Marlana Orloff,&nbsp;David J Eschelman,&nbsp;Carlin F Gonsalves,&nbsp;Robert D Adamo,&nbsp;Pramila R Anne,&nbsp;Jason J Luke,&nbsp;Devron Char,&nbsp;Takami Sato","doi":"10.1089/cbr.2021.0366","DOIUrl":"https://doi.org/10.1089/cbr.2021.0366","url":null,"abstract":"<p><p><b><i>Background:</i></b> Liver metastases from uveal melanoma carry a very poor prognosis. Hepatic artery infusions with Yttrium-90 (⁹⁰Y) resin microspheres have some activity in this disease, and radiation and immunotherapy may be synergistic. The primary objective of this study was to determine the safety and tolerability of sequential ⁹⁰Y resin microspheres and immunotherapy with ipilimumab and nivolumab in metastatic uveal melanoma. <b><i>Materials and Methods:</i></b> Twenty-six patients with uveal melanoma with hepatic metastases were entered into a pilot study. Treatment consisted of two infusions of ⁹⁰Y resin microspheres, one to each lobe of the liver, followed in 2-4 weeks by immunotherapy with ipilimumab and nivolumab every 3 weeks for four doses, then maintenance immunotherapy with nivolumab alone. <b><i>Results:</i></b> Initial dosing of both ⁹⁰Y and immunotherapy resulted in excessive toxicity. With decreasing the dosage of ⁹⁰Y to limit the normal liver dose to 35Gy and lowering the ipilimumab dose to 1 mg/kg, the toxicity was tolerable, with no apparent change in efficacy. There was one complete and four confirmed partial responses, for an objective response rate of 20% and a disease control rate of 68%. The median progression-free survival was 5.5 months (95% confidence interval [CI]: 1.3-9.7 months), with a median overall survival of 15 months (95% CI: 9.7-20.1 months). <b><i>Conclusions:</i></b> With dose reductions, sequential therapy with ⁹⁰Y and immunotherapy with ipilimumab and nivolumab is safe and tolerable, and has activity in metastatic uveal melanoma. These results justify a controlled trial to demonstrate whether ⁹⁰Y resin microspheres add to the utility of combination immunotherapy in this disease. Clinical Trial Registration number: NCT02913417.</p>","PeriodicalId":518937,"journal":{"name":"Cancer biotherapy & radiopharmaceuticals","volume":" ","pages":"11-16"},"PeriodicalIF":3.4,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8861913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39928820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chelation-Tamoxifen Conjugates for Imaging of Estrogen Receptors.","authors":"Skye Hsin-Hsien Yeh,&nbsp;Wei-Chung Chang,&nbsp;Shu-Meng Hsu,&nbsp;Ming Hsien Lin,&nbsp;Min-Ching Chung,&nbsp;Chi-Shiang Ke,&nbsp;Yen-Chun Lee,&nbsp;Chorng-Jer Hwang,&nbsp;David J Yang","doi":"10.1089/cbr.2021.0169","DOIUrl":"https://doi.org/10.1089/cbr.2021.0169","url":null,"abstract":"<p><p><b><i>Background:</i></b> The differential diagnosis of estrogen receptor-positive (ER+) pathway-activated systems by using a labeled antiestrogen helps to select the patients for optimal response to endocrine therapy and to discontinue the treatment when resistance occurs. The authors' purpose was to synthesize chelator-tamoxifen conjugates for imaging ER (+) diseases. <b><i>Materials and Methods:</i></b> A hydroxypropyl linker was incorporated between either cyclam or cyclam diacetic acid and tamoxifen analog to produce SC-05-L-1 (Z-1-(1,4,8,11-tetraazacyclotetradecan-1-yl)-3-((5-(4-(2-(diethylamino)ethoxy)phenyl)-4,5-diphenylpent-4-en-1-yl)oxy)propan-2-ol) and SC-05-N-1 (Z-2,2'-(4-(3-((5-(4-(2-(diethylamino)ethoxy)phenyl)-4,5-diphenylpent-4-en-1-yl)oxy)-2-hydroxy-propyl)-1,4,8,11-tetraazacyclotetradecane-1,8-diyl)diacetic acid), respectively. <i>In vitro</i> cell uptake and cell/media ratios of ^99mTc-SC-05-L-1 and ^99mTc- SC-05-N-1 in ER (+) ovarian cancer cells (TOV-112D and OVCAR3) were performed. To ascertain the specificity of cell uptake, the cell uptake was blocked with estrone. <i>In vivo</i> ^99mTc-SC-05-L-1 or ^99mTc-SC-05-N-1 single-photon emission computed tomography/computed tomography was conducted in tumor-bearing rodents and compared to ¹⁸F-fluoro-2-deoxy-d-glucose (¹⁸F-FDG) positron emission tomography/magnetic resonance imaging (a reference technology). <b><i>Results:</i></b> The radiochemical purities of ^99mTc-SC-05-L-1 and ^99mTc-SC-05-N-1 were greater than 99% (<i>n</i> = 10). ^99mTc-SC-05-L-1 had higher cell/media ratios than ^99mTc-SC-05-N-1 in OVCAR-3 ER (+) cells. The cell uptake of ^99mTc-SC-05-L-1 was blocked 80% by estrone indicating an ER-mediated process occurred. ^99mTc-SC-05-N-1 was further selected for <i>in vivo</i> imaging studies due to higher maximum tolerated dose and superior water solubility than ^99mTc-SC-05-L-1. ^99mTc-SC-05-N-1 showed higher tumor uptake and tumor/muscle count density ratios than ¹⁸F-FDG in tumor-bearing rodents. <b><i>Conclusion:</i></b> ^99mTc-SC-05-N-1 showed better differential diagnosis of ovarian tumors than ¹⁸F-FDG, indicating great promising in chelator-tamoxifen conjugate for ER pathway-directed systems imaging.</p>","PeriodicalId":518937,"journal":{"name":"Cancer biotherapy & radiopharmaceuticals","volume":" ","pages":"30-40"},"PeriodicalIF":3.4,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39394371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}