Theragnostic Gadolinium-Based Nanoparticles Safely Augment X-ray Radiation Effects in Patients with Cervical Cancer.
ACS Nano
; 18(26): 16516-16529, 2024 Jul 02.
Article
in En
| MEDLINE
| ID: mdl-38912600
ABSTRACT
Activated guided irradiation by X-ray (AGuIX) nanoparticles are gadolinium-based agents that have the dual benefit of mimicking the effects of a magnetic resonance imaging (MRI) contrast agent used in a clinical routine and enhancing the radiotherapeutic activity of conventional X-rays (for cancer treatment). This "theragnostic" action is explained on the one hand by the paramagnetic properties of gadolinium and on the other hand by the generation of high densities of secondary radiation following the interaction of ionizing radiation and high-Z atoms, which leads to enhanced radiation dose deposits within the tumors where the nanoparticles accumulate. Here, we report the results of a phase I trial that aimed to assess the safety and determine the optimal dose of AGuIX nanoparticles in combination with chemoradiation and brachytherapy in patients with locally advanced cervical cancer. AGuIX nanoparticles were administered intravenously and appropriately accumulated within tumors on a dose-dependent manner, as assessed by T1-weighted MRI, with a rapid urinary clearance of uncaught nanoparticles. We show that the observed tumor accumulation of the compounds can support precise delineation of functional target volumes at the time of brachytherapy based on gadolinium enhancement. AGuIX nanoparticles combined with chemoradiation appeared well tolerated among the 12 patients treated, with no dose-limiting toxicity observed. Treatment yielded excellent local control, with all patients achieving complete remission of the primary tumor. One patient had a distant tumor recurrence. These results demonstrate the clinical feasibility of using theranostic nanoparticles to augment the accuracy of MRI-based treatments while focally enhancing the radiation activity in tumors.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Magnetic Resonance Imaging
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Uterine Cervical Neoplasms
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Nanoparticles
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Gadolinium
Limits:
Adult
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Aged
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Female
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Humans
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Middle aged
Language:
En
Journal:
ACS Nano
Year:
2024
Document type:
Article
Affiliation country:
Country of publication: