Abstract
Glioblastoma is the most aggressive primary brain tumor leading to death in most of patients. It comprises almost 50–55% of all gliomas with an incidence rate of 2–3 per 100,000. Despite its rarity, overall mortality of glioblastoma is comparable to the most frequent tumors. The current standard treatment combines surgical resection, radiotherapy and chemotherapy with temozolomide. In spite of this aggressive multimodality protocol, prognosis of glioblastoma is poor and the median survival remains about 12–14.5 months. In this regard, new therapeutic approaches should be developed to improve the life quality and survival time of the patient after the initial diagnosis. Before switching to clinical trials in humans, all innovative therapeutic methods must be studied first on a relevant animal model in preclinical settings. In this regard, we validated the feasibility of intratumoral delivery of a holmium (Ho) microparticle suspension to an induced U87 glioblastoma model. Among the different radioactive beta emitters, 166Ho emits high-energy β(-) radiation and low-energy γ radiation. β(-) radiation is an effective means for tumor destruction and γ rays are well suited for imaging (SPECT) and consequent dosimetry. In addition, the paramagnetic Ho nucleus is a good asset to perform MRI imaging. In this study, five minipigs, implanted with our glioblastoma model were used to test the injectability of 165Ho (stable) using a bespoke injector and needle. The suspension was produced in the form of Ho microparticles and injected inside the tumor by a technique known as microbrachytherapy using a stereotactic system. At the end of this trial, it was found that the 165Ho suspension can be injected successfully inside the tumor with absence or minimal traces of Ho reflux after the injections. This injection technique and the use of the 165Ho suspension needs to be further assessed with radioactive 166Ho in future studies.
Highlights
Glioblastoma (GB) is an inherently aggressive tumor and by far the most frequent and lethal malignant primary brain tumor in adults [1,2,3,4]
The intratumoral injectability of the 165Ho siloxane suspension was tested in preclinical studies with the minipig (Yucatan) GB model
Some parameters were modified in the injection system and treatment planning (TP) during the test on these five animals to improve injection control and optimize the results of the intratumoral administration of the 165Ho
Summary
Glioblastoma (GB) is an inherently aggressive tumor and by far the most frequent and lethal malignant primary brain tumor in adults [1,2,3,4]. The gold-standard treatment protocol is a maximal surgical resection of the tumor, plus RT with concurrent and adjuvant medical chemotherapy, such as Temozolomide (TMZ) [5]. New treatments, such as immunotherapy, have emerged but results for these new modalities are not yet conclusive [14,15,16,17]. GB is associated with an extremely poor prognosis [7,18,19] and patients are often confronted with a recurrence of the disease after a few months [2,15,20,21]
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