Cancer Biotherapy and Radiopharmaceuticals最新文献

{"title":"Breaks for Precision Medicine in Cancer: Development and Prospects of Spatiotemporal Transcriptomics.","authors":"Shiqi Yan, Yilin Guo, Lizhong Lin, Wenling Zhang","doi":"10.1089/cbr.2023.0116","DOIUrl":"10.1089/cbr.2023.0116","url":null,"abstract":"<p><p>With the development of the social economy and the deepening understanding of cancer, cancer has become a significant cause of death, threatening human health. Although researchers have made rapid progress in cancer treatment strategies in recent years, the overall survival of cancer patients is still not optimistic. Therefore, it is essential to reveal the spatial pattern of gene expression, spatial heterogeneity of cell populations, microenvironment interactions, and other aspects of cancer. Spatiotemporal transcriptomics can help analyze the mechanism of cancer occurrence and development, greatly help precise cancer treatment, and improve clinical prognosis. Here, we review the integration strategies of single-cell RNA sequencing and spatial transcriptomics data, summarize the recent advances in spatiotemporal transcriptomics in cancer studies, and discuss the combined application of spatial multiomics, which provides new directions and strategies for the precise treatment and clinical prognosis of cancer.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"35-45"},"PeriodicalIF":3.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139106942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NOTCH Signaling Pathway: Occurrence, Mechanism, and NOTCH-Directed Therapy for the Management of Cancer.","authors":"Lakshmi Kumari, Lopamudra Mishra, Yash Sharma, Kanak Chahar, Mritunjay Kumar, Preeti Patel, Ghanshyam Das Gupta, Balak Das Kurmi","doi":"10.1089/cbr.2023.0023","DOIUrl":"10.1089/cbr.2023.0023","url":null,"abstract":"<p><p>It is now well understood that many signaling pathways are vital in carrying out and controlling essential pro-survival and pro-growth cellular functions. The NOTCH signaling pathway, a highly conserved evolutionary signaling pathway, has been thoroughly studied since the discovery of NOTCH phenotypes about 100 years ago in <i>Drosophila melanogaster</i>. Abnormal NOTCH signaling has been linked to the pathophysiology of several diseases, notably cancer. In tumorigenesis, <i>NOTCH</i> plays the role of a \"double-edged sword,\" that is, it may act as an oncogene or as a tumor suppressor gene depending on the nature of the context. However, its involvement in several cancers and inhibition of the same provides targeted therapy for the management of cancer. The use of gamma (γ)-secretase inhibitors and monoclonal antibodies for cancer treatment involved NOTCH receptors inhibition, leading to the possibility of a targeted approach for cancer treatment. Likewise, several natural compounds, including curcumin, resveratrol, diallyl sulfide, and genistein, also play a dynamic role in the management of cancer by inhibition of NOTCH receptors. This review outlines the functions and structure of NOTCH receptors and their associated ligands with the mechanism of the signaling pathway. In addition, it also emphasizes the role of NOTCH-targeted nanomedicine in various cancer treatment strategies.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"19-34"},"PeriodicalIF":3.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41154165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Feasibility of One-Day PET/CT Scanning Protocol with ⁶⁸Ga-DOTA-FAPI-04 and ¹⁸F-FDG for the Detection of Ovarian Cancer Recurrence and Metastasis.","authors":"Yunuan Liu, Xiaoshan Chen, Fenglian Jing, Xinming Zhao, Zhaoqi Zhang, Jingmian Zhang, Jianfang Wang, Meng Dai, Na Wang, Tingting Wang, Xiaolin Chen","doi":"10.1089/cbr.2023.0085","DOIUrl":"10.1089/cbr.2023.0085","url":null,"abstract":"<p><p><b><i>Objective:</i></b> The objective of this study was to investigate the feasibility of 1-d ⁶⁸Ga-DOTA-FAPI-04 and ¹⁸F-FDG (2-deoxy-2[¹⁸F]fluoro-d-glucose) positron emission tomography/computed tomography (PET/CT) for detecting ovarian cancer recurrence and metastasis. <b><i>Materials and Methods:</i></b> Fifty-two patients who underwent ¹⁸F-FDG and ⁶⁸Ga-DOTA-FAPI-04 PET/CT were divided into 1- and 2-d groups. Image acquisition, injection time, and total waiting time were compared. For the ⁶⁸Ga-DOTA-FAPI-04 PET/CT scans, low-dose CT scans and low injection dosages were employed, and total radiation dose was assessed for both protocols. The comparative analysis included assessment of patient-based detection rates and lesion-based diagnostic efficacy. <b><i>Results:</i></b> The total waiting time was significantly shorter in the 1-d group than in the 2-d group (<i>p</i> = 0.000). The radiation doses stemming from internal radiation and external radiation between the groups showed no differences (<i>p</i> = 0.151 vs. 0.716). In the patient-based analysis, the detection rates for local recurrence, peritoneal, lymph node, and other metastases were not significantly different in both protocols (<i>p</i> ∈ [0.351, 1.000]). For the lesion-based analysis, no differences were noted in terms of sensitivity, specificity, positive predictive value, negative predictive value, and accuracy (<i>p</i> ∈ [0.371, 1.000]). <b><i>Conclusions:</i></b> The 1-d PET/CT protocol reduced waiting time and exhibited equivalent detectability compared with the 2-d protocol, suggesting its clinical value.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"55-63"},"PeriodicalIF":3.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54232379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel Method for Real-Time Quantification of Radioligand Binding to Living Tumor Cells <i>In Vitro</i>.","authors":"Tom Bäck, Per Albertsson, Emma Aneheim, Ragnar Hultborn, Lars Jacobsson, Sture Lindegren, Stig Palm","doi":"10.1089/cbr.2022.0093","DOIUrl":"10.1089/cbr.2022.0093","url":null,"abstract":"<p><p><b><i>Background:</i></b> Real-time quantification of radioligand binding to cells under <i>in vivo</i>-like conditions improves evaluation of clinical potential. <b><i>Materials and Methods:</i></b> SKOV-3 tumor cells were grown in a monolayer on a thin glass plate placed in a sealable shallow chamber with a continuous flow of ¹²⁵I-trastuzumab solution. The time-dependent cell binding was measured using a NaI detector, and the binding parameters were derived by computational analysis. <b><i>Results:</i></b> The detection efficiency of ¹²⁵I was 65 cps/kBq for radioligand bound to the cells. Experiments were analyzed to find the values of <i>k</i>_on and <i>k</i>_off. The resulting <i>k</i>_on was 3.2-7.9 × 10⁴ M^-1 s^-1 and <i>k</i>_off was 0.11-4.2 × 10^-5 s^-1. <b><i>Conclusions:</i></b> Radioligands can be rapidly evaluated by binding to living cells for selection and optimization of radioconjugates for diagnostic and therapeutic purposes.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"75-81"},"PeriodicalIF":3.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10880261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139543980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis, Quality Control, and Bench-to-Bed Translation of a New [⁶⁸Ga]Ga-Labeled NOTA-Conjugated Bisphosphonate for Imaging Skeletal Metastases by Positron Emission Tomography.","authors":"Sudipta Chakraborty, Sucheta Chatterjee, Rubel Chakravarty, Haldhar D Sarma, Raviteja Nanabala, Dibakar Goswami, Ajith Joy, Maroor Raghavan Ambikalamajan Pillai","doi":"10.1089/cbr.2023.0077","DOIUrl":"10.1089/cbr.2023.0077","url":null,"abstract":"<p><p><b><i>Background</i></b>: Early detection of skeletal metastasis is of great interest to determine the prognosis of cancer. Positron emission tomography-computed tomography (PET-CT) imaging provides a better temporal and spectral resolution than single photon emission computed tomography-computed tomography (SPECT-CT) imaging, and hence is more suitable to detect small metastatic lesions. Although [¹⁸F]NaF has been approved by U.S. FDA for a similar purpose, requirement of a medical cyclotron for its regular formulation restricts its extensive utilization. Efforts have been made to find suitable alternative molecules that can be labeled with ⁶⁸Ga and used in PET-CT imaging. <b><i>Objective:</i></b> The main objective of this study is to synthesize and evaluate a new [⁶⁸Ga]Ga-labeled NOTA-conjugated geminal bisphosphonate for its potential use in early detection of skeletal metastases using PET-CT. <b><i>Methods:</i></b> The authors performed a multistep synthesis of a new NOTA-conjugated bisphosphonic acid using thiourea linker and radiolabeled the molecule with ⁶⁸Ga. The radiolabeled formulation was evaluated for its <i>in vitro</i> stability, affinity for hydroxyapatite (HA) particles, preclinical biodistribution in animal models, and PET-CT imaging in patients. <b><i>Results:</i></b> The bifunctional chelator (NOTA)-conjugated bisphosphonate was synthesized with 97.8% purity and radiolabeled with ⁶⁸Ga in high yield (>98%). The radiolabeled formulation was found to retain its stability <i>in vitro</i> to the extent of >95% up to 4 h in physiological saline and human serum. The formulation also showed high affinity for HA particles <i>in vitro</i> with <i>K_d</i> = 907 ± 14 mL/g. Preclinical biodistribution studies in normal Wistar rats demonstrated rapid and almost exclusive skeletal accumulation of the complex. PET-CT imaging in a patient confirmed its ability to detect small metastatic skeletal lesions. <b><i>Conclusions:</i></b> The newly synthesized [⁶⁸Ga]Ga-labeled NOTA-conjugated bisphosphonate is a promising radiotracer for PET-CT imaging for skeletal metastases.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"92-101"},"PeriodicalIF":3.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139713470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Re: \"Noncoding RNAs Interplay in Ovarian Cancer Therapy and Drug Resistance\" by Liu et al.","authors":"Belma Gözde Özdemir","doi":"10.1089/cbr.2023.0167","DOIUrl":"10.1089/cbr.2023.0167","url":null,"abstract":"","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"102"},"PeriodicalIF":3.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138801636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acknowledgment of Reviewers 2023.","authors":"","doi":"10.1089/cbr.2023.29016.ack","DOIUrl":"10.1089/cbr.2023.29016.ack","url":null,"abstract":"","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":"39 1","pages":"103"},"PeriodicalIF":3.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139747850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Prognostic Role of [¹⁸F]FDG PET/CT in Patients with Advanced Cutaneous Squamous Cell Carcinoma Submitted to Cemiplimab Immunotherapy: A Single-Center Retrospective Study.","authors":"Luca Filippi, Ilaria Proietti, Vincenzo Petrozza, Concetta Potenza, Oreste Bagni, Orazio Schillaci","doi":"10.1089/cbr.2023.0110","DOIUrl":"10.1089/cbr.2023.0110","url":null,"abstract":"<p><p><b><i>Background:</i></b> Baseline 2-deoxy-2[¹⁸F]fluoro-d-glucose ([¹⁸F]FDG) positron emission tomography (PET)-derived parameters and 12-week metabolic response were investigated as prognostic factors in advanced cutaneous squamous cell carcinoma (cSCC) submitted to cemiplimab immunotherapy. <b><i>Materials and Methods:</i></b> Clinical records of 25 cSCC patients receiving cemiplimab, submitted to [¹⁸F]FDG positron emission tomography/computed tomography (PET/CT) at baseline and after ∼12 weeks, were retrospectively reviewed. The Kaplan-Meier (KM) method was applied to analyze differences in event-free survival (EFS), and Cox regression analysis was employed to identify the prognostic factors. <b><i>Results:</i></b> At the 12-week PET/CT evaluation, 16 patients (64%) were classified as responders (complete or partial response) and 9 (36%) as nonresponders (\"unconfirmed progressive metabolic disease\") according to immune PET Response Criteria in Solid Tumors (iPERCIST). By KM analysis, baseline metabolic tumor volume (MTV) and total lesion glycolysis (TLG) significantly correlated with the EFS (<i>p</i> < 0.05). Furthermore, the KM analysis showed that the lack of metabolic response at 12 weeks was associated with meaningfully shorter EFS (7.2 ± 1 months in nonresponders vs. 20.3 ± 2.3 months in responders). In Cox multivariate analysis, metabolic response at 12 weeks remained the only predictor of the EFS (<i>p</i> < 0.05). <b><i>Conclusions:</i></b> Baseline tumor load (i.e., MTV and TLG) and metabolic response at 12 weeks may have a prognostic impact in cSCC patients treated with cemiplimab.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"46-54"},"PeriodicalIF":3.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54232380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of ¹⁷⁷Lu-Labeled Pertuzumab F(ab')₂ Fragments for HER2-Positive Cancer Targeting: A Comparative <i>In Vitro</i> and <i>In Vivo</i> Study.","authors":"Rohit Sharma, Archana Mukherjee, Anuj Kumar, Haladhar Dev Sarma","doi":"10.1089/cbr.2023.0108","DOIUrl":"10.1089/cbr.2023.0108","url":null,"abstract":"<p><p><b><i>Background:</i></b> Radiolabeled antibody fragments present a promising opportunity as theranostic agents, offering distinct advantages over whole antibodies. In this study, the authors investigate the potential of [¹⁷⁷Lu]Lu-DTPA-F(ab')₂-pertuzumab as a theranostic agent for precise targeting of human epidermal growth factor receptor 2 (HER2)-positive cancers. Additionally, the authors aim to quantitatively assess the binding synergism in the presence of cold trastuzumab. <b><i>Materials and Methods:</i></b> F(ab')₂-pertuzumab was prepared by pepsin digestion and conjugated with a bifunctional chelator. The immunoconjugate was radiolabeled with ¹⁷⁷Lu and characterized by chromatography techniques. Binding parameters (affinity, specificity, and immunoreactivity) and cellular binding enhancement studies were evaluated in HER2-overexpressing and triple-negative cell lines. The <i>in vivo</i> enhancement in tumor uptake of the radiolabeled immunoformulation was assessed in severe combined immunodeficient (SCID) mice bearing tumors, both in the presence and absence of unlabeled trastuzumab. <b><i>Results:</i></b> The formulation of [¹⁷⁷Lu]Lu-DTPA-F(ab')₂-pertuzumab could be prepared in high yields and with consistent radiochemical purity, ensuring reproducibility. Comprehensive <i>in vitro</i> and <i>in vivo</i> evaluation studies confirmed high specificity and immunoreactivity of the formulation toward HER2 receptors. Binding synergism of radiolabeled pertuzumab fragments in the presence of trastuzumab to HER2 receptors was observed. <b><i>Conclusions:</i></b> The radioformulation of [¹⁷⁷Lu]Lu-DTPA-F(ab')₂-pertuzumab holds great promise as a targeted approach for addressing HER2-positive cancers. A potentially effective strategy to amplify therapeutic efficacy involves dual epitope targeting by combining radiolabeled pertuzumab with cold trastuzumab.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":"39 1","pages":"64-74"},"PeriodicalIF":3.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139747851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Precision Deuteration in Search of Anticancer Agents: Approaches to Cancer Drug Discovery.","authors":"Aman Mourya, Navnit Prajapati","doi":"10.1089/cbr.2023.0031","DOIUrl":"10.1089/cbr.2023.0031","url":null,"abstract":"<p><p>Cancer chemotherapy has been shifted from conventional cytotoxic drug therapy to selective and target-specific therapy after the findings about DNA changes and proteins that are responsible for cancer. A large number of newer drugs were discovered as targeted therapy for particular types of neoplastic disease. The initial discovery includes the development of the first in the category, imatinib, a Bcr-Abl tyrosine kinase inhibitor (TKI) for the treatment of chronic myelocytic leukemia in 2001. But the joy did not last for long as the drug developed a point mutation within the ABL1 kinase domain of BCR-ABL1, which subsequently led to the discovery of many other TKIs. Resistance was observed for newer TKIs a few years after their launching, but the use of TKIs in life-threatening cancer therapy is considered as far better compared with the risks of disease because of its target specificity and hence less toxicity. In search of a better anticancer agent, the physiochemical properties of the lead molecule have been modified for its efficacy toward disease and delay in the development of resistance. Deuteration in the drug molecule is one of such modifications that alter the pharmacokinetic properties, generally its metabolism, as compared with its pharmacodynamic effects. Precision deuteration in many anticancer drugs has been carried out to search for better drugs for cancer. In this review, the majority of anticancer drugs and molecules for which deuteration was applied to get better anticancer molecules were discussed. This review will provide a complete guide about the benefits of deuteration in cancer chemotherapy.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"1-18"},"PeriodicalIF":3.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10016144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}