Division of Neurosurgery, University Hospitals, Basel, Switzerland.
Eur J Nucl Med Mol Imaging. 2010 Jul;37(7):1335-44. doi: 10.1007/s00259-010-1385-5. Epub 2010 Feb 16.
Functionally critically located gliomas represent a challenging subgroup of intrinsic brain neoplasms. Standard therapeutic recommendations often cannot be applied, because radical treatment and preservation of neurological function are contrary goals. The successful targeting of gliomas with locally injected beta radiation-emitting (90)Y-DOTAGA-substance P has been shown previously. However, in critically located tumours, the mean tissue range of 5 mm of (90)Y may seriously damage adjacent brain areas. In contrast, the alpha radiation-emitting radionuclide (213)Bi with a mean tissue range of 81 microm may have a more favourable toxicity profile. Therefore, we evaluated locally injected (213)Bi-DOTA-substance P in patients with critically located gliomas as the primary therapeutic modality.
In a pilot study, we included five patients with critically located gliomas (WHO grades II-IV). After diagnosis by biopsy, (213)Bi-DOTA-substance P was locally injected, followed by serial SPECT/CT and MR imaging and blood sampling. Besides feasibility and toxicity, the functional outcome was evaluated.
Targeted radiopeptide therapy using (213)Bi-DOTA-substance P was feasible and tolerated without additional neurological deficit. No local or systemic toxicity was observed. (213)Bi-DOTA-substance P showed high retention at the target site. MR imaging was suggestive of radiation-induced necrosis and demarcation of the tumours, which was validated by subsequent resection.
This study provides proof of concept that targeted local radiotherapy using (213)Bi-DOTA-substance P is feasible and may represent an innovative and effective treatment for critically located gliomas. Primarily non-operable gliomas may become resectable with this treatment, thereby possibly improving the prognosis.
功能上关键部位的胶质瘤是一类具有挑战性的颅内原发性肿瘤。由于根治性治疗与神经功能保留相矛盾，标准的治疗建议往往无法应用。先前已证实局部注射β射线放射性核素（90）Y-DOTAGA-神经肽可靶向治疗胶质瘤。然而，在关键部位的肿瘤中，（90）Y 的平均组织射程为 5mm 可能会严重损害邻近的脑区。相比之下，α射线放射性核素（213）Bi 的平均组织射程为 81μm，可能具有更有利的毒性特征。因此，我们评估了局部注射（213）Bi-DOTA-神经肽作为主要治疗方式在关键部位胶质瘤患者中的应用。
在一项初步研究中，我们纳入了 5 例关键部位的胶质瘤患者（WHO 分级Ⅱ-Ⅳ级）。经活检确诊后，局部注射（213）Bi-DOTA-神经肽，随后进行连续 SPECT/CT 和 MRI 成像以及血液取样。除了可行性和毒性外，还评估了功能结局。
使用（213）Bi-DOTA-神经肽的靶向放射性肽治疗是可行的，且无额外的神经功能缺损，患者可耐受。未观察到局部或全身毒性。（213）Bi-DOTA-神经肽在靶部位有高保留。MRI 成像提示肿瘤存在放射性坏死和边界，随后的切除也证实了这一点。
本研究提供了概念验证，即使用（213）Bi-DOTA-神经肽的靶向局部放疗是可行的，可能代表了治疗关键部位胶质瘤的一种创新且有效的方法。通过这种治疗，主要的不可切除性胶质瘤可能变得可切除，从而可能改善预后。
