Cancer Biotherapy and Radiopharmaceuticals最新文献

{"title":"Investigation into the Spatial Heterogeneity of Lung Composite Large-Cell Neuroendocrine Carcinoma Spatial Transcriptomic Analysis of Combined Large-Cell Neuroendocrine Carcinoma.","authors":"Mingyu Ji, Daming Fan, Yaqi Yuan, Jing Wang, Xiaodong Feng, Weihua Yang, Xiaofei Dang, Yihui Xu, Jun Wang","doi":"10.1089/cbr.2025.0043","DOIUrl":"https://doi.org/10.1089/cbr.2025.0043","url":null,"abstract":"<p><p><b><i>Background:</i></b> Lung combined large-cell neuroendocrine carcinoma (CoLCNEC) refers to lung regions exhibiting both the features of large-cell neuroendocrine carcinoma (LCNEC) and the defined components of nonsmall cell lung cancer (NSCLC), with a relatively high mitotic rate. Diagnosing and predicting the prognosis of CoLCNEC are challenging. This study aimed to explore spatial transcriptomic expression patterns and identify crucial genes. <b><i>Methods:</i></b> We utilized a sample from a CoLCNEC patient containing three distinct components, namely, LCNEC, adenocarcinoma, and squamous cell carcinoma, with the former being predominant. Spatial transcriptomics (ST) technology, which employs the 10× Genomics Visium formalin-fixed paraffin-embedded ST kit, was applied along with high-throughput sequencing to obtain gene expression information and spatial locations for each spot. Subsequent analysis included differentially gene expression and functional enrichment. Finally, immunohistochemistry was employed to validate the marker protein structural maintenance of chromosomes 1A (<i>SMC1A</i>). Then, <i>SMC1A</i> was overexpressed and silenced in NCI-H661 and LTEP-a-2 cells, and the migration and invasion ability of the cells were detected by scratch assay and Transwell, respectively. The role of <i>SMC1A</i> in cancer cell cycle was detected by Real-time Reverse Transcription-PCR(RT-qPCR), Western blot, and flow cytometry, the apoptosis was detected by flow cytometry. <b><i>Results:</i></b> The results revealed that tumor tissue regions had higher unique molecular identifiers and gene counts than nontumor regions did. Unsupervised clustering identified four clusters, revealing the uniform distribution of unique transcripts, which were mapped onto slices to display apparent spatial separation. Differentially gene expression analysis revealed genes highly expressed in cancer cells. Further analysis of different regions revealed distinct cellular subgroups enriched through differentially gene expression analysis in various pathways, such as the cell cycle and DNA replication. Finally, <i>SMC1A</i> was chosen as a candidate gene, and immunohistochemistry confirmed its elevated expression in tumor regions. In addition, compared with oe-NC, oe-<i>SMC1A</i> can significantly promote the migration, invasion and G1/S phase transition of lung cancer cells, and promote the inhibition of apoptosis of cancer cells, while sh-<i>SMC1A</i> is completely opposite. <b><i>Conclusions:</i></b> In the tumor region of CoLCNEC, <i>SMC1A</i> is significantly upregulated. Moreover, silencing <i>SMC1A</i> effectively inhibits lung cancer cell invasion, migration, and G1/S phase transition, while promoting apoptosis. These findings indicate that <i>SMC1A</i> has the potential to be a new therapeutic target for CoLCNEC treatment.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144041276","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":"Applications of Nanobodies in Biological Imaging.","authors":"Liangjü Sheng, Kai Sheng, Peng Lü","doi":"10.1089/cbr.2025.0005","DOIUrl":"https://doi.org/10.1089/cbr.2025.0005","url":null,"abstract":"<p><p><b><i>Background:</i></b> Nanobodies (Nbs), derived from Camelidae heavy-chain antibodies, are single-domain fragments (15 kDa) with high antigen-binding specificity, enhanced tissue penetration, and low immunogenicity. These attributes address limitations of conventional antibodies, positioning Nbs as pivotal tools for targeted molecular imaging in diagnostics and therapeutics. <b><i>Methods:</i></b> Nbs are screened through phage/mRNA display or single B-cell sequencing, expressed in prokaryotic or yeast systems, and humanized via CDR grafting. Functional probes are engineered by conjugating Nbs with radionuclides (⁶⁸Ga, ⁹⁹mTc) or fluorophores (IRDye 800CW) for compatibility with PET, SPECT, NIRF, and ultrasound modalities. <b><i>Results:</i></b> Clinical trials validated Nb efficacy: ⁶⁸Ga-HER2-Nb PET/CT achieved tumor-specific uptake in HER2+ cancers (NCT04467515), while 99mTc-PD-L1-Nb enabled quantitative SPECT-guided immunotherapy in NSCLC. NIRF-Nb conjugates (e.g., 11A4-800CW) enhanced intraoperative tumor delineation in murine models. Dual-targeted ultrasound microbubbles demonstrated multi-biomarker imaging via acoustic pressure modulation. <b><i>Conclusion:</i></b> Nbs advance biological imaging through superior resolution and rapid pharmacokinetics. Challenges persist in optimizing probe stability, minimizing immunogenicity, and scaling production. Future priorities include integrating multi-modal platforms, expanding applications to neurodegenerative disorders, and refining personalized diagnostic paradigms, underscoring their transformative potential in precision medicine.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144060855","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":"Immunotherapeutics in Clinical Trials for Cervical Cancer.","authors":"Umarani Yadagiri, Rahaman Shaik, Rajini Kolure, Tatheer Fatima, Huda Khan","doi":"10.1089/cbr.2025.0031","DOIUrl":"https://doi.org/10.1089/cbr.2025.0031","url":null,"abstract":"<p><p>The fourth most common cause of cancer-related deaths in women is cervical cancer (CC) in the worldwide. Although there are differences in the accessibility of therapies across developed and developing nations, an improvement in survival rate has been observed in patients with precancerous lesions, thanks to the development of precancerous lesion identification and preventative human papillomavirus vaccination programs. Surgery can cure early-stage CC, but patients who experience a recurrence have a poor prognosis and few therapy alternatives. Recently, it has been demonstrated that the drug bevacizumab increases overall survival in this latter context when combined with chemotherapy as opposed to chemotherapy administered alone. Beyond this therapy regimen, there are no established treatments. Therefore, in this situation, new, effective treatments are desperately needed. Immunotherapy has been a revolutionary treatment.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144059054","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":"Small Animal Positron Emission Tomography Imaging of a Triple-Negative Breast Cancer Model Using the ⁶⁸Ga-Labeled pH (Low) Insertion Peptide-Like Peptide YJL-11.","authors":"Mingming Yu, Fengyu Wu, Yanqin Sun, Shuangshuang Song, Yuehua Chen","doi":"10.1089/cbr.2024.0230","DOIUrl":"https://doi.org/10.1089/cbr.2024.0230","url":null,"abstract":"<p><p><b><i>Objectives:</i></b> To prepare a novel ⁶⁸Ga-labeled pH (low) insertion peptide-like peptide, YJL-11, and study its ability to be used as a probe for the diagnosis of triple-negative breast cancer (TNBC) via <i>in vivo</i> imaging of tumor-bearing nude mice. <b><i>Methods:</i></b> Circular dichroism (CD) analysis of YJL-11 was performed to assess its secondary structure. YJL-11 was labeled with ⁶⁸Ga, and the <i>in vivo</i> biodistribution of ⁶⁸Ga-YJL-11 in MDA-MB-231 xenograft mice was evaluated. This probe was then applied for small animal positron emission tomography (PET) imaging of tumor-bearing nude mice. <b><i>Results:</i></b> CD analysis of YJL-11 confirmed a typical pH-dependent transition in its secondary structure. The radiochemical yield of ⁶⁸Ga-YJL-11 was 75.5 ± 0.25%, and the radiochemical purity was 95.75 ± 0.15%. Biodistribution studies showed that the tumor uptake of ⁶⁸Ga-YJL-11 was significantly higher than in the control group, 1 and 2 h after injection. Small animal PET imaging results were consistent with the biodistribution data, showing clear images of the tumors and livers 1 and 2 h after injection of ⁶⁸Ga-YJL-11, whereas tumors were not detected in the control group. <b><i>Conclusion:</i></b> ⁶⁸Ga-YJL-11 was prepared with high radiochemical yield and can target TNBC tissues, indicating that it has great potential in the diagnosis of TNBC.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144018495","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":"High Expression of Complement 3 Enhances the Efficacy of Neoadjuvant Chemotherapy Prior to Oncoplastic Surgery for HER2-Positive Breast Cancer.","authors":"Bo Chen, Lifen Huang, Morui Gui, Luz Angela Torres-de la Roche, Rudy Leon De Wilde, Wenjie Shi, Hui Liu, Zhenyu Gong","doi":"10.1089/cbr.2025.0038","DOIUrl":"https://doi.org/10.1089/cbr.2025.0038","url":null,"abstract":"<p><p><b><i>Background:</i></b> Neoadjuvant chemotherapy for breast cancer (BC) improves patient prognosis, but its efficacy is hindered by the disease's high heterogeneity. This study enhances effectiveness of targeted therapy to improve clinical outcomes. <b><i>Methods:</i></b> This study enrolled 335 patients from three centers. Differentially expressed genes were identified using DESeq2, and Venn analysis was applied to identify hub Complement genes. Hub gene expression was validated through public databases and IHC in real-world samples. In addition, associations between these genes and clinical factors were evaluated. Survival analysis, using the log-rank test, assessed overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) as end points. The authors also locate hub Complement 3 gene position by immunofluorescence. <b><i>Results:</i></b> The study identified <i>C3</i> as a hub Complement gene associated with trastuzumab sensitivity. C3 shows higher expression in normal than tumor tissues. C3 was highly expressed in HER2-negative and early-stage BC, but showed no differences in lymph node or metastasis subgroups. High C3 expression correlated with better OS, DSS, and PFI, particularly in HER2+ patients. IHC analysis confirmed higher C3 expression in normal tissues with the lowest in triple-negative BC. Immunofluorescence findings suggest that C3 recruits complement receptor 2 to enhance trastuzumab efficacy in HER2+ patients. <b><i>Conclusions:</i></b> This finding highlights the potential of complement 3 to improve therapeutic outcomes and pave the way for more personalized treatment strategies in BC.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143996210","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":"Collagen Hydrogel Loaded With 9-cisRA-Lip Is an Option for Treatment of Secondary Lymphedema after Surgery.","authors":"Min Yao, Jinrong Wei, Lijie Chen, Chunyan Li, Guo-Qin Jiang","doi":"10.1089/cbr.2024.0177","DOIUrl":"10.1089/cbr.2024.0177","url":null,"abstract":"<p><p><b><i>Background:</i></b> Secondary upper limb lymphedema commonly occurs after breast cancer surgery, for which treatment is limited. 9-cis-retinoic acid (9-cisRA) has been demonstrated to increase lymphangiogenesis without enhancing tumor metastasis but has disadvantages of poor water solubility, ready decomposition in light, instability to heat, and a short half-life. <b><i>Methods:</i></b> Based on this, 9-cisRA-Lip with a particle size of roughly 143 nm and high dispersibility was prepared by thin-film dispersion method and verified by Malvern Laser Particle Size Analyzer and electron microscopy. <b><i>Results:</i></b> <i>In vitro</i>, 9-cisRA-Lip demonstrated good biosafety and tumor safety, promoting the proliferation of L929 cells while having no effect on 4T1 and Human Umbilical Vein Endothelial (HUVEC) cells. Compared with 9-cisRA, 9-cisRA-Lip was more effective at stimulating mouse lymphatic endothelial cell (SVEC4-10) migration, proliferation, and tube formation. <i>In vivo</i>, 9-cisRA-Lip-Gel showed good slow release effect. Mice treated with 9-cisRA-Lip-Gel one-time local injection had considerably less tail edema than the control group from day 9 to day 39 postsurgery (<i>p</i> < 0.05). This may be attributed to the greater capacity of 9-cisRA-Lip to enhance the phosphorylation of <i>FGFR3</i> (Fibroblast Growth Factor Receptor 3) at <i>Tyr 724</i>. <b><i>Conclusions:</i></b> 9-cisRA-Lip-Gel presents a potential treatment option for lymphedema following surgery.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"210-218"},"PeriodicalIF":2.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142752247","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":"Intuitive Human-Artificial Intelligence Theranostic Complementarity.","authors":"J Harvey Turner","doi":"10.1089/cbr.2025.0021","DOIUrl":"10.1089/cbr.2025.0021","url":null,"abstract":"<p><p>Deep learning artificial intelligence (AI) algorithms are poised to subsume diagnostic imaging specialists in radiology and nuclear medicine, where radiomics can consistently outperform human analysis and reporting capability, and do it faster, with greater accuracy and reliability. However, claims made for generative AI in respect of decision-making in the clinical practice of theranostic nuclear medicine are highly contentious. Statistical computer algorithms cannot emulate human emotion, reason, instinct, intuition, or empathy. AI simulates intelligence without possessing it. AI has no understanding of the meaning of its outputs. The unique statistical probability attributes of large language models of AI must be complemented by the innate human intuitive capabilities of nuclear physicians who accept the responsibility and accountability for direct clinical care of each individual patient referred for theranostic management of specified cancers. Complementarity envisions synergistic engagement with AI radiomics, genomics, radiobiology, dosimetry, and data collation from multidimensional sources, including the electronic medical record, to enable the nuclear physician to spend informed face time with their patient. Together with physician discernment, application of the technical insights from AI will facilitate optimal formulation of a personalized precision theranostic strategy for empathic, efficacious, targeted treatment of the patient with cancer in accordance with their wishes.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"153-160"},"PeriodicalIF":2.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143460874","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":"Generalized Seizure as an Acute post-[¹⁷⁷Lu]Lu-DOTATATE Side Effect in a Case of Recurrent Meningioma.","authors":"Abdolmajid Alipour, Tahereh Ghaedian, Abbas Rakhsha, Mehrnaz Ghaedian, Babak Yazdani","doi":"10.1089/cbr.2024.0222","DOIUrl":"10.1089/cbr.2024.0222","url":null,"abstract":"<p><p>[¹⁷⁷Lu]Lu-DOTATATE is a newly trending acceptable therapy in recurrent/residual meningioma with good safety. However, recognizing any possible side effects in this special population would be helpful for better management and individualization of this useful treatment. Although the seizure has been previously reported in a few cases after [¹⁷⁷Lu]Lu-DOTATATE therapy in recurrent meningioma, the acute onset of seizure in these patients, early after therapeutic radioligand administration, is not reported to the best of our knowledge. This report presents a case with the progression of residual meningioma after previous surgery in 2016 who developed with generalized tonic-clonic seizure, a few hours after administration of 200 mCi [¹⁷⁷Lu]Lu-DOTATATE. The patient was taking prophylactic doses of the lacosamide, although no previous history of seizure was reported.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"228-230"},"PeriodicalIF":2.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142916494","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":"METTL3 and HERC4: Elevated Expression and Impact on Hepatocellular Carcinoma Progression.","authors":"Tao Sun, Shiyu Geng, Qingjing Ru, Yi Zheng","doi":"10.1089/cbr.2024.0126","DOIUrl":"10.1089/cbr.2024.0126","url":null,"abstract":"<p><p><b><i>Background:</i></b> Methyltransferase-like 3 (METTL3) and HECT and RLD domain containing E3 ubiquitin protein ligase 4 (HERC4) have been studied in the field of oncology; however, their roles and interaction in hepatocellular carcinoma (HCC) await elucidation. <b><i>Methods:</i></b> Initially, METTL3 and HERC4 expressions in normal and HCC samples were predicted employing the UALCAN database, and the targeting relationship between these two was explored via coimmunoprecipitation assay. Following the quantification on N6-methyladenosine (m⁶A) enrichment, the localization of METTL3 and HERC4 on HCC cells was visualized via immunofluorescence assay. The effects of METTL3 and HERC4 on HCC cells proliferation and migration were determined <i>in vitro</i> assays. METTL3 and HERC4 expressions were quantified via quantitative polymerase chain reaction, and those of metastasis-related proteins N-cadherin and vimentin were calculated with immunoblotting assay. Furthermore, the levels of angiogenic factors such as vascular endothelial growth factor and basic fibroblast growth factor were measured by enzyme-linked immunosorbent assay. <b><i>Results:</i></b> METTL3 and HERC4 expressed highly in HCC and their expressions were positively correlated with tumor grade. METTL3 overexpression enhanced the expression of HERC4 and promoted the proliferation and migration abilities of HCC cells. Specifically, METTL3 overexpression increased vimentin and N-cadherin expressions, while its silencing did conversely. Besides, HERC4 overexpression reversed the effects of METTL3 silencing on the proliferation and migration as well as the levels of angiogenic factors in HCC cells. <b><i>Conclusion:</i></b> This study reveals the upregulation of METTL3 and HERC4 expression in HCC and their role in HCC by enhancing the proliferation, migration, and angiogenesis potential of HCC cells.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"173-184"},"PeriodicalIF":2.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142752248","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":"Intratumoral Distribution of [¹⁷⁷Lu]Lu-PSMA-617 Over Time and in Relation to Diagnostic Tracers in Animal Models of Prostate Cancer.","authors":"Anders Örbom, Joanna Strand, Mohamed Altai, Wahed Zedan, Amanda Kristiansson, Jens Ceder, Oskar Vilhelmsson Timmermand","doi":"10.1089/cbr.2024.0170","DOIUrl":"10.1089/cbr.2024.0170","url":null,"abstract":"<p><p><b><i>Introduction:</i></b> Prostate-specific membrane antigen (PSMA) is a target for diagnostic positron emission tomography (PET)-tracers and radiopharmaceutical therapy (RPT), for example, [¹⁷⁷Lu]Lu-PSMA-617, in prostate cancer. This autoradiography study investigates [¹⁷⁷Lu]Lu-PSMA-617 intratumoral distribution over time, compared with PSMA expression, proliferation (Ki67), and [⁶⁸Ga]Ga-PSMA-11, [¹⁸F]F-PSMA-1007, [¹⁸F]-fluorodeoxyglucose, and [¹⁸F]-fluorocholine distribution. Mice with LNCaP, 22Rv1, or PC-3 PIP xenografts got [¹⁷⁷Lu]Lu-PSMA-617 i.v. Sacrificed 1 h p.i. if coinjected with diagnostic tracers, otherwise at 20 min, 1-2, 12, 24, 48, 72 h, or 2-3 weeks p.i. Cryosectioned tumors imaged by autoradiography, adjacent sections Ki67 or PSMA stained. <b><i>Results:</i></b> Heterogeneous distribution of [¹⁷⁷Lu]Lu-PSMA-617 was seen 20 min p.i., with visible overlap between tumor cells, Ki67, PSMA, and radioactivity at 1-2 h p.i. Strongest Ki67-correlation at 48 h, which became negative at 72 h and beyond with some Ki67+/PSMA+ low radioactivity areas. Uptake in necrotic tissue was only observed at 2-3 weeks p.i. PSMA-targeted tracers distributed identically to [¹⁷⁷Lu]Lu-PSMA-617 whereas other tracers only had some overlap. <b><i>Conclusion:</i></b> Regrowth of the tumor post-[¹⁷⁷Lu]Lu-PSMA-617 administration creates Ki67+/PSMA+ areas that have no radioactivity uptake and need additional therapy fractions. The identical intratumoral distribution of [¹⁷⁷Lu]Lu-PSMA-617 and PSMA-targeted PET-tracers indicate that these will reveal the areas inside the tumor targeted by RPT at least at 1 h p.i.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"219-227"},"PeriodicalIF":2.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142741506","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}