Comparison of 64Cu-DOTA-PSMA-3Q and 64Cu-NOTA-PSMA-3Q utilizing NOTA and DOTA as bifunctional chelators in prostate cancer: preclinical assessment and preliminary clinical PET/CT imaging.
Objective: This study aims to investigate the efficacy and safety of prostate-specific membrane antigen (PSMA) radiolabeled with copper-64 (64Cu) using the bifunctional chelating agents (BFCAs) NOTA (1,4,7-triazacyclononane-1,4,7-triacetic acid) and DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetr...
| Publicado en: | European Journal of Nuclear Medicine & Molecular Imaging Vol. 52; no. 8; pp. 2792 - 2804 |
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| Autores principales: | , , , , , , , , , , , , |
| Formato: | Journal Article |
| Publicado: |
Springer Nature
Jul2025
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=185941774&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 185941774 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 16197070 NPC jtl: European Journal of Nuclear Medicine & Molecular Imaging issn: 16197070 maglogo: N pubinfo: dt: Jul2025 vid: 52 iid: 8 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 185941774 183018539 10.1007/s00259-025-07131-3 185941774 ppf: 2792 ppct: 12 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Comparison of 64Cu-DOTA-PSMA-3Q and 64Cu-NOTA-PSMA-3Q utilizing NOTA and DOTA as bifunctional chelators in prostate cancer: preclinical assessment and preliminary clinical PET/CT imaging. aug: au: Liu, Huanhuan Zhang, Xiaojun Zhang, Jingfeng Pan, Yue Wen, Hui Xu, Xiaodan Wu, Shina Wang, Yuan Zhang, Cong Ma, Guangyu Liu, Yachao Wang, Ruimin Zhang, Jinming affil: https://ror.org/04gw3ra78 Department of Nuclear Medicine, The First Medical Centre, Chinese PLA General Hospital, No. 28 Fuxing Road, Haidian District, 100853, Beijing, China sug: ab: Objective: This study aims to investigate the efficacy and safety of prostate-specific membrane antigen (PSMA) radiolabeled with copper-64 (64Cu) using the bifunctional chelating agents (BFCAs) NOTA (1,4,7-triazacyclononane-1,4,7-triacetic acid) and DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid). As widely utilized BFCAs in the development of radiopharmaceuticals, NOTA and DOTA play a critical role in ensuring stable chelation with 64Cu. This study evaluates the stability, bioavailability, and therapeutic potential of these radiolabeled compounds in preclinical models and initial clinical trials. Methods: 64Cu-DOTA-PSMA-3Q and 64Cu-NOTA-PSMA-3Q were synthesized by manual labeling. The radiochemical purity, stability, specificity and biological distribution of the product were evaluated by preclinical studies. In 23 patients with suspected prostate cancer, PET/CT imaging was used to evaluate the potential and differences in biological distribution of 64Cu-DOTA-PSMA-3Q and 64Cu-NOTA-PSMA-3Q in clinical diagnosis. Results: The radiochemical purities of 64Cu-DOTA-PSMA-3Q and 64Cu-NOTA-PSMA-3Q are more than 98% and have good stability in vitro. Biodistribution studies in healthy mice revealed that both tracers primarily underwent renal excretion post-injection. Liver uptake of 64Cu-DOTA-PSMA-3Q was significantly higher than that of 64Cu-NOTA-PSMA-3Q at 1 h after injection (P<0.05). Micro-PET/CT imaging in 22Rv1 tumor-bearing mice demonstrated similar tumor uptake for both tracers at 1 h after injection (P>0.05). However, after 24 h, 64Cu-DOTA-PSMA-3Q exhibited significantly better tumor retention compared to 64Cu-NOTA-PSMA-3Q (P<0.05). In clinical PET/CT imaging involving 23 patients with suspected prostate cancer, no adverse reactions or significant changes in vital signs were observed, underscoring the safety of both tracers. Notably, 64Cu-NOTA-PSMA-3Q demonstrated higher uptake in the lacrimal glands (17.73 vs. 10.84), parotid glands (20.98 vs. 16.30), and submandibular glands (20.26 vs. 17.28) compared to 64Cu-DOTA-PSMA-3Q. Conversely, uptake in the sublingual glands was lower for 64Cu-NOTA-PSMA-3Q (7.10 vs. 7.49). Of particular clinical relevance, liver uptake of 64Cu-NOTA-PSMA-3Q was significantly lower than that of 64Cu-DOTA-PSMA-3Q (4.04 vs. 8.18), highlighting a key difference in their biodistribution profiles. Conclusions: Both NOTA and DOTA are suitable chelators for the development of 64Cu-labeled PSMA-3Q tracers for PET/CT imaging. DOTA showed better tumor retention 24 h after injection, while NOTA showed lower uptake in the liver, in addition, NOTA was higher uptake in the salivary glands, while DOTA was lower uptake in these tissues. Overall, these findings highlight the importance of selecting the right chelating agent to optimize clinical imaging outcomes. Trial registration: Chinese Clinical Trial Registry ChiCTR2300072655, Registered 20 June 2023. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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