Synthesis and Preclinical Evaluation of Dual-Specific Probe Targeting Glypican-3 and Prostate-Specific Membrane Antigen for Hepatocellular Carcinoma PET Imaging DOI
Lixing Chen, Siyuan Cheng,

Dongling Zhu

et al.

Molecular Pharmaceutics, Journal Year: 2024, Volume and Issue: 22(1), P. 209 - 220

Published: Dec. 10, 2024

Positron emission tomography (PET) is a promising modality for early diagnosis, accurate detection, and staging of hepatocellular carcinoma (HCC). Hereby, dual-specific probe targeting Glypican-3 (GPC3) prostate-specific membrane antigen (PSMA) was evaluated HCC PET imaging. The prepared by conjugating TJ12P2, GPC3-targeting peptide previously reported our group, to highly potent PSMA inhibitor via polyethylene glycol linker further tethered the 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) chelator. resultant probe, NOTA-TJ12P2-PSMA, abbreviated as T2P, labeled with gallium-68 fluorine-18, respectively, in murine models various levels GPC3 expression. Targeting specificity confirmed blocking studies. synthesized [

Language: Английский

Current advance of nanotechnology in diagnosis and treatment for malignant tumors DOI Creative Commons

Bilan Wang,

Shiqi Hu, Yan Teng

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Aug. 12, 2024

Cancer remains a significant risk to human health. Nanomedicine is new multidisciplinary field that garnering lot of interest and investigation. shows great potential for cancer diagnosis treatment. Specifically engineered nanoparticles can be employed as contrast agents in diagnostics enable high sensitivity high-resolution tumor detection by imaging examinations. Novel approaches labeling are also made possible the use nanoprobes nanobiosensors. The achievement targeted medication delivery therapy accomplished through rational design manufacture nanodrug carriers. Nanoparticles have capability effectively transport medications or gene fragments tissues via passive active targeting processes, thus enhancing treatment outcomes while minimizing harm healthy tissues. Simultaneously, context radiation sensitization photothermal enhance therapeutic efficacy malignant tumors. This review presents literature overview summary how nanotechnology used According oncological diseases originating from different systems body combining pathophysiological features cancers at sites, we most recent developments applications. Finally, briefly discuss prospects challenges cancer.

Language: Английский

Citations

87
Theranostics - a sure cure for cancer after 100 years? DOI Creative Commons
Yangmeihui Song, Jianhua Zou, Ernesto Castellanos

et al.

Theranostics, Journal Year: 2024, Volume and Issue: 14(6), P. 2464 - 2488

Published: Jan. 1, 2024

Cancer has remained a formidable challenge in medicine and claimed an enormous number of lives worldwide.Theranostics, combining diagnostic methods with personalized therapeutic approaches, shows huge potential to advance the battle against cancer.This review aims provide overview theranostics oncology: exploring its history, current advances, challenges, prospects.We present fundamental evolution from radiotherapeutics, cellular therapeutics, nanotherapeutics, showcasing critical milestones last decade.From early concept targeted drug delivery emergence medicine, benefited advances imaging technologies, molecular biology, nanomedicine.Furthermore, we emphasize pertinent illustrations that revolutionary strategies cancer management enhance accuracy therapies customized for individual patients, thereby facilitating implementation medicine.Finally, describe future perspectives on emerging topics, field.

Language: Английский

Citations

15
Therapeutic synthetic and natural materials for immunoengineering DOI Creative Commons

Anna Slezak,

Kevin Chang,

Samir Hossainy

et al.

Chemical Society Reviews, Journal Year: 2024, Volume and Issue: 53(4), P. 1789 - 1822

Published: Jan. 1, 2024

This review discusses the balance of inflammation in immunity and biomaterials strategies to modulate cases imbalance such as autoimmune disease, infection, cancer. Adapted from “Balanced Energy State”, by BioRender.com (2023).

Language: Английский

Citations

11
Prostate-specific membrane antigen-targeted surgery in prostate cancer: Accurate identification, real-time diagnosis, and precise resection DOI Creative Commons
Jianhua Jiao, Jingjing Zhang, Weihong Wen

et al.

Theranostics, Journal Year: 2024, Volume and Issue: 14(7), P. 2736 - 2756

Published: Jan. 1, 2024

Radical prostatectomy (RP) combined with pelvic lymph node dissection (PLND) is the first step in multimodal treatment of prostate cancer (PCa) without distant metastases.For a long time, surgical resection range has been highly dependent on surgeon's visualization and experience preoperative imaging.With rapid development prostate-specific membrane antigen positron emission tomography single-photon computed (PSMA-PET PSMA-SPECT), PSMA-targeted surgery introduced for more accurate pathological diagnosis complete positive margins (PSMs) micro-lymph metastases (LNMs).We reviewed surgeries, including PSMA-PET-guided prostatic biopsy (PSMA-TB), radio-guided (PSMA-RGS), fluorescence-guided (PSMA-FGS), multi-modality/multi-targeted surgery.We also discuss strengths challenges surgery, propose that could be great addition to existing protocols, thereby improving accuracy convenience primary recurrent PCa near future.

Language: Английский

Citations

6
Effect of Linker Entities on Pharmacokinetics of 111In-Labeled Prostate-Specific Membrane Antigen-Targeting Ligands with an Albumin Binder DOI

Nobuki Kazuta,

Kazuma Nakashima, Hiroyuki Watanabe

et al.

ACS Pharmacology & Translational Science, Journal Year: 2024, Volume and Issue: 7(8), P. 2401 - 2413

Published: July 9, 2024

In the field of radiopharmaceutical development targeting cancer, an albumin binder (ALB) is commonly used to improve accumulation radioligands in tumors because it has high binding affinity for and extends circulation time radioligands. The further ALB-containing also expected regulate their pharmacokinetics. this study, we newly designed synthesized [111In]In-PNT-DA1 derivatives, prostate-specific membrane antigen (PSMA)-targeting including a functional linker (d-glutamic acid or 4-(aminomethyl)benzoic acid), evaluated relationships among structure, albumin-binding affinity, These derivatives showed different by introduction linker. Biodistribution studies revealed that affects pharmacokinetics each derivative. biodistribution suggested moderate enhances tumor/kidney ratio SPECT imaging using [111In]In-PNT-DA3 with highest led clear visualization PSMA-positive LNCaP tumor. results suggest appropriate entities may be necessary PSMA-targeting

Language: Английский

Citations

4
Preclinical and First-in-Human Study of a Compact Radionuclide Labeled Self-Assembly Nanomedicine for Chemo-Radio-Theranostics of Cancer DOI

Hehe Xiong,

Rongxi Wang, Heng Zhang

et al.

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 13, 2025

The emerging combination of chemotherapy and radionuclide therapy has been actively investigated to overcome the limitations monotherapy augment therapeutic efficacy. However, it remains a challenge design single delivery vehicle that can incorporate chemotherapeutics radionuclides into compact structure. Here, chelator DOTA- or NOTA-modified Evans blue conjugated camptothecin molecule (EB-CPT) nanoprodrug was synthesized, which could self-assemble nanoparticles due its inherent amphiphilicity. then be effectively labeled with lutetium-177 (177Lu) diagnostic gallium-68 (68Ga)/copper-64 (64Cu) high radiolabeling efficiency radiochemical stability. Impressively, single-dose chemoradiation [177Lu]Lu-DOTA-EB-CPT plus EB-CPT inhibited tumor growth in HCT116 tumor-bearing mice compared respective individual approach. [64Cu]Cu-NOTA-EB-CPT also exhibited excellent vivo characteristics including favorable blood circulation properties prolonged retention mice. safety, feasibility, tolerability, biodistribution [68Ga]Ga-NOTA-EB-ss-CPT were preliminarily characterized first-in-human study. This study presents simple but robust radiopharmaceutical leverages EB as an albumin binder strike delicate balance between enhanced accumulation, efficacy, facilitating integrated theranostic strategy within molecular radionuclide-labeled nanomedicine step toward clinical translation radiotheranostics.

Language: Английский

Citations

0
A new NCL-targeting aptamer-drug conjugate as a promising therapy against esophageal cancer DOI Creative Commons
Xue Zheng, Ying Wang, Huaiyu Duan

et al.

Journal of Nanobiotechnology, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 28, 2025

Language: Английский

Citations

0
Synthesis and Imaging of Novel CDK19‐Targeted Tracers Incorporating an Albumin‐Binding Moiety DOI
Panfeng Li,

Zhao Yang,

Yanli Li

et al.

Journal of Labelled Compounds and Radiopharmaceuticals, Journal Year: 2025, Volume and Issue: 68(3)

Published: March 1, 2025

ABSTRACT Cyclin‐dependent kinase 19 (CDK19) is a potential target for the diagnosis and treatment of prostate cancer. We have previously studied series CDK19‐targeted PET tracers, but in‐depth drug optimization needed to improve physiochemical properties such large polar tracers. The albumin strategy has received widespread attention in recent years, we synthesized 68 Ga‐IRM‐14a Ga‐IRM‐14b based on strategy. After vivo imaging studies mice, found that introducing moiety will significantly change physicochemical existing polarity thereby increasing tissue uptake retention, which beneficial future treatment. In short, be an important field radiopharmaceutical optimization.

Language: Английский

Citations

0
Dansylated Amino Acid–Modified Long-Acting PSMA Derivatives68Ga/177Lu-LNC1011 as Prostate Cancer Theranostics DOI

Hongzhang Yang,

Jiarou Wang,

Xuejun Wen

et al.

Journal of Nuclear Medicine, Journal Year: 2025, Volume and Issue: unknown, P. jnumed.124.268959 - jnumed.124.268959

Published: March 20, 2025

Prostate-specific membrane antigen (PSMA)-targeted radiopharmaceutical therapy has demonstrated promising potential for treating metastatic castration-resistant prostate cancer. Recently, albumin-binding motif-modified PSMA radioligands with prolonged blood circulation were developed to improve tumor uptake and therapeutic effectiveness, properties which, however, associated an increased risk of bone marrow toxicity. This study presents new PSMA-targeted incorporating dansylated amino acids as relatively weak preferable albumin binders achieve a fine balance between accumulation, safety, diagnostic efficacy, facilitating unified approach theranostics within single molecular framework. Methods: Three novel ligands ([68Ga]Ga-Dan-Gly-PSMA, [68Ga]Ga-Dan-Nva-PSMA, [68Ga]Ga-Dan-Phe-PSMA, denoted [68Ga]Ga-LNC1011) synthesized measured the human serum through ultrafiltration experiments. Binding affinity PSMA-targeting specificity investigated using saturation binding assay cell in PSMA-induced cancer 3 line (PC3-PIP). PET imaging PC3-PIP tumor-bearing mice was performed evaluate preclinical pharmacokinetics efficiency 68Ga-labeled ligands. Tumor [177Lu]Lu-LNC1011 evaluated SPECT/CT biodistribution studies. Radiopharmaceutical studies conducted systematically assess effect radioligand. Results: various successfully radiochemical yield greater than 97%. In xenograft model, tumor/heart, tumor/liver, tumor/kidney, tumor/muscle ratios 9.82 ± 2.35, 12.42 3.71, 4.36 0.29, 52.88 12.08 at 4 h after injection, respectively. Biodistribution confirmed significantly higher (127.36 16.95 %ID/g) over [177Lu]Lu-PSMA-617 (17.44 6.29 no decrease up 72 which corroborated SPECT imaging. A injection 9.3 MBq achieved 89.43% inhibition growth, equivalent 18.5 (90.87%). [68Ga]Ga-LNC1011 PET/CT scans patients identified many lesions [68Ga]Ga-PSMA-11 did, confirming its efficacy. Conclusion: 68Ga/177Lu-LNC1011, characterized by high retention along timely clearance from normal organs tissues, thus emerges single-molecule theranostic

Language: Английский

Citations

0
Preclinical Characterization of Novel FAP-2286-Based Radioligand with Albumin Binder for Improved Tumor Retention DOI

K. Saito,

Hiroyuki Watanabe, Kazuma Nakashima

et al.

ACS Medicinal Chemistry Letters, Journal Year: 2025, Volume and Issue: unknown

Published: March 23, 2025

Fibroblast activation protein (FAP) is an attractive biomarker for tumor-targeting agents in cancer diagnosis and therapy. FAP-2286 shows retention FAP-expressing tumors known as a promising FAP-targeting radioligand. In this study, we aimed to develop derivative that demonstrates higher tumor than FAP-2286. We designed DOTAGA-FAP-2286 DOTAGA-FAP-2286-ALB by replacing DO3A with 2-(4,7,10-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecan-1-yl)pentanedioic acid (DOTAGA) introducing albumin binder. Both compounds were successfully radiolabeled 111In. Compared [111In]In-DOTAGA-FAP-2286, [111In]In-DOTAGA-FAP-2286-ALB showed stability murine plasma. the cell competition binding In-DOTAGA-FAP-2286-ALB exhibited FAP-binding affinity In-DOTAGA-FAP-2286. albumin-binding assay, high rate solution albumin. The biodistribution assay revealed marked of [111In]In-DOTAGA-FAP-2286-ALB, resulting enhancement predicted AUC values [225Ac]Ac-DOTAGA-FAP-2286-ALB. These results suggest advantages introduction binder

Language: Английский

Citations

0