Development and Evaluation of Novel ⁶⁸Ga/¹⁷⁷Lu-Labeled PSMA Inhibitors with Enhanced Pharmacokinetics and Tumor Imaging for Prostate Cancer

Molecular Pharmaceutics, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 14, 2025

Prostate-specific membrane antigen (PSMA) has been a key target for diagnosing and treating prostate cancer, particularly in high-grade, metastatic, therapy-resistant tumors. This study presents series of novel 68Ga- 177Lu-labeled PSMA inhibitors, derived from the previously developed [68Ga]Ga-Flu-1. We explored impact PEG chains, lipophilic macrocycles, dimerization on their vivo properties. The inhibitors were assessed biodistribution tumor targeting PC3-PIP xenografts, leading to identification several promising candidates based imaging tumor-specific uptake. Positron emission tomography (PET) revealed that poly(ethylene glycol)-modified [68Ga]Ga-BisPSMA-P4 demonstrated rapid penetration excellent tumor-to-background contrast. In comparative studies, naphthalene ring-modified [68Ga]Ga-BisPSMA-Nph-P4 showed higher uptake (∼60% ID/g at 1 h postinjection) renal clearance (∼25% 2 postinjection). Additionally, [177Lu]Lu-BisPSMA-Nph-P4 displayed superior retention, with significant day 7, highlighting its potential as inhibitor cancer diagnosis treatment.

Language: Английский

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Sharpening the Blade of Precision Theranostics

Seminars in Nuclear Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

While theranostics is a new term for long-standing principles in nuclear medicine, recent advances have facilitated more personalized healthcare and precision medicine. Despite the widespread enthusiasm well established standardized procedures, there are number of opportunities to enhance practice sharpen blade theranostics. A clear understanding requisites an authentic theranostic pair reveals limitations current approaches. Indeed, dosing regimes based on activity dose as opposed absorbed highlight potential enhancements outcomes medicine that predictive dosimetry could bring. Such increase demand closer matching biological chemical properties pairs. In turn, need or true pairs revealed. has provided revolutionary toolkit cancer management, instrumentation, radiochemistry clinical domains requires similar remaining domains. This discussion explores key considerations evolving landscape, recognising best may fall short over coming years.

Language: Английский

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New frontiers in the pharmacological management of biliary tract carcinomas: the emerging role of drug conjugates

Expert Opinion on Pharmacotherapy, Journal Year: 2025, Volume and Issue: unknown

Published: April 17, 2025

Biliary tract cancer (BTC) is a human malignancy with poor prognosis. However, significant progress has been made in understanding the molecular mechanisms of carcinogenesis, leading to development targeted therapy strategies recent years. The challenge now develop new therapeutic concepts further increase efficacy BTC treatments coming This review covers emerging and advanced approaches highly sophisticated antibody-drug conjugates (ADCs) non-ADCs, particularly relation BTC. Additionally, potential advantages disadvantages ADCs non-ADCs regarding toxicities, bioavailability, are presented discussed. Given prognosis BTCs, precision using drug - without antibodies as carriers have overcome limitations conventional chemotherapy by improving treatment specificity while reducing systemic toxicity. several open questions remain including chemical design, delivery, related diagnostic biomarkers, combinatory application strategies.

Language: Английский

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68Ga-Trivehexin: Current Status of αvβ6-Integrin Imaging and Perspectives

Cancers, Journal Year: 2025, Volume and Issue: 17(9), P. 1504 - 1504

Published: April 29, 2025

Molecular imaging, especially PET, has advanced significantly, shifting from metabolic radiotracers like 2-deoxy-2-[18F]fluoro-D-glucose [18F]FDG to target-specific probes. Among these, αvβ6-integrin emerged as a promising target in cancer and non-cancer diseases. This review focuses on the radiochemical properties initial clinical applications of [68Ga]Ga-Trivehexin PET probe. The literature systematically evaluated both preclinical studies, with particular emphasis its characteristics preliminary applications, while highlighting advancements, associated challenges, potential for future developments field. study highlights significant advancements achieved field molecular imaging. optimized multimeric system substantially enhanced radiotracer's pharmacokinetic properties, binding affinity, selectivity αvβ6 integrin, demonstrating up an 18-fold improvement compared previous monomeric tracers. synthesis protocol been refined achieve high purity (>95%), essential safe use. Preliminary particularly head neck (HNC) pancreatic ductal adenocarcinoma (PDAC), have shown results, detection rates improved differential diagnosis [18F]FDG. Furthermore, PET/CT non-oncological conditions, such idiopathic pulmonary fibrosis (IPF) primary hyperthyroidism, suggesting broader applicability. is probe imaging cancers diseases hyperparathyroidism (PHP).

Language: Английский

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Boric acid functionalized carbon nanotheranostic platform for the hierarchical delivery of immune adjuvants and chemotherapy agents

Journal of Drug Delivery Science and Technology, Journal Year: 2025, Volume and Issue: unknown, P. 106993 - 106993

Published: May 1, 2025

Language: Английский

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Intra-arterial administration of PSMA-targeted radiopharmaceuticals for brain tumors: is the era of interventional theranostics next?

Expert Review of Anticancer Therapy, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 5

Published: Aug. 29, 2024

In recent years, prostate-specific membrane antigen (PSMA), a transmembrane glycoprotein, has emerged as promising biomarker for theranostics, integrating diagnosis and therapy. PSMA's overexpression in various tumors, including brain metastases high-grade gliomas, suggests its potential neuro-oncology. Pruis et al. conducted proof-of-concept study comparing intra-arterial (IA) intravenous (IV) administration of

Language: Английский

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Evaluation of Environmental Radiation Exposure and Algorithms for Determining the Occupational Effective Dose During 99mTc-MDP Bone Scintigraphy: A Comprehensive Analysis

Applied Sciences, Journal Year: 2024, Volume and Issue: 14(23), P. 11211 - 11211

Published: Dec. 2, 2024

This study evaluated the occupational exposure of radiopharmacists, nurses, radiological technologists, and technologist assistants involved in 99mTc-MDP bone scintigraphy procedures. Actual effective doses for individual staff needed ascertaining. An environmental radiation audit revealed all nuclear medicine areas were compliant with ICRP IAEA guidelines. To ascertain doses, they recorded by OSL badges. The highest was to Hp(0.07) 2.19 µSv during radiolabeling. nurse administering a dose 0.27 at Hp(0.07), 26.01% total dose. assistant receive 73.05% However, received positioning patients SPECT/CT scans, an 32.03 µSv. Single double dosimetry estimate algorithms evaluated, resulting being more accurate. Padovani et al. algorithm found most closely align actual values (p > 0.05), thereby validating measurement methods used this study. research offers benchmark applicable audits continuous effort enhance safety personnel scintigraphy.

Language: Английский

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Human–Artificial Intelligence Symbiotic Reporting for Theranostic Cancer Care

Cancer Biotherapy and Radiopharmaceuticals, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 5, 2024

Reporting of diagnostic nuclear images in clinical cancer management is generally qualitative. Theranostic treatment with 177Lu radioligands for prostate and neuroendocrine tumors routinely given as the same arbitrary fixed administered activity to every patient. Nuclear oncology, currently practiced 177Lu-prostate-specific membrane antigen peptide receptor radionuclide therapy, cannot, therefore, be characterized personalized precision medicine. The evolution artificial intelligence (AI) could change this "one-size-fits-all" approach theranostics, through development a symbiotic relationship physicians. Combining quantitative data collection, collation, analytic computing power AI algorithms expertise, empathy, personal care patients by their physician envisions new paradigm theranostic reporting molecular imaging radioligand cancer. Human–AI interaction will facilitate compilation comprehensive, integrated medicine report. This holistic report would incorporate radiomics quantitatively analyze digital prospectively calculate radiation absorbed dose tumor critical normal organs. therapy then accurately prescribed deliver preordained, effective, tumoricidal tumor, while minimizing toxicity particular Post-therapy validate actual delivered sequential pre- post-treatment dosimetry each cycle allow individual prescription monitoring over entire course treatment. Furthermore, use analysis predict likely outcome, predicated upon definition biology, pathology, genomics, correlated history laboratory data. Such synergistic comprehensive enable self-assurance who necessarily deemed personally responsible accountable outcome. Paradoxically, may thus expected enhance practice phronesis foster truly empathic trusting

Language: Английский

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Application of 99mTc-FAPI-46 Imaging in a Patient With Medullary Thyroid Carcinoma

Clinical Nuclear Medicine, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 31, 2024

Abstract We present the case of a 58-year-old man with metastatic medullary thyroid carcinoma refractory to conventional therapies, including peptide receptor radionuclide therapy. Despite multiple interventions, serum calcitonin and carcinoembryonic antigen levels continued rise. Subsequent evaluation 99m Tc-FAPI-46 revealed remarkable uptake in lesions, suggesting potential role for FAPI-labeled radioisotopes management carcinoma. This underscores emerging utility FAPI-targeted radiotracers oncologic nuclear medicine highlights need further research this promising area.

Language: Английский

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Prostate-Specific Membrane Antigen-Positron Emission Tomography-Guided Radiomics and Machine Learning in Prostate Carcinoma

Cancers, Journal Year: 2024, Volume and Issue: 16(19), P. 3369 - 3369

Published: Oct. 1, 2024

Positron emission tomography (PET) using radiolabeled prostate-specific membrane antigen targeting PET-imaging agents has been increasingly used over the past decade for imaging and directing prostate carcinoma treatment. Here, we summarize available literature data on radiomics machine learning these in carcinoma. Gleason scores derived from biopsy after resection are discordant a large number of patients. Available studies suggest that applied to PSMA-radioligand avid primary might be better performing than biopsy-based Gleason-scoring could serve as an alternative non-invasive GS characterization. Furthermore, it may allow prediction biochemical recurrence with net benefit clinical utilization. Machine based PET/CT features was also shown able differentiate benign malignant increased tracer uptake PSMA-targeting radioligand examinations, thus paving way fully automated image reading nuclear medicine. As treatment outcome following 177Lu-PSMA therapy overall survival, limited have reported promising results images this purpose. Its added value parameters warrants further exploration larger datasets

Language: Английский

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