RDC Development for Glioblastoma Multiforme

RDC (Radionuclide Drug Conjugate) can be used for the treatment of glioblastoma multiforme by targeting molecules and radionuclides that have a damaging effect on the tumor cells.

Introduction into Glioblastoma Multiforme

Glioblastoma Multiforme (GBM), also known as glioblastoma, is one type of Gliomas, one of the most common groups of primary brain tumors, which can be divided into three types, including astrocytomas, oligodendrogliomas, and ependymomas. According to WHO (World Health Organization) based on certain pathological features, such as nuclear atypia, mitotic activity, vascular proliferation, necrosis, proliferative potential and features clinical course and treatment outcome, Gliomas are subdivided into grade III/IV tumors and grade IV/IV tumors, which includes glioblastoma multiforme.

Causes and Symptoms of Glioblastoma Multiforme

In the Clinical, patients with glioblastoma multiforme may present with headaches, focal neurologic deficits, confusion, memory loss, personality changes, or seizures, which can be detected by MRI (Magnetic Resonance Imaging), combined with other adjunct technologies such as functional MRI, diffusion-weighted imaging, diffusion tensor imaging, dynamic contrast-enhanced MRI, perfusion imaging, SPECT (Single Photon Emission Computed Tomography) and PET (Positron Emission Tomography).

Glioblastoma multiforme may be induced by several environmental risk factors, including primary exposure to therapeutic ionizing radiation and factors such as vinyl chloride or pesticides, smoking, petroleum refining or production work, and employment in synthetic rubber manufacturing, as well as a number of additional factors, including exposure to residential electromagnetic fields, formaldehyde, and irradiation.

Traditional Therapeutic Effect of Glioblastoma Multiforme

Glioblastoma multiforme is the most common malignant primary brain tumor, incidence of which is 3.19 cases per 100 thousand people years with a remarkably poor prognosis in clinical trials, presented as a 5-year survival rate of 4-5%, and a 2-year survival rate of 26-33%.

The standard treatment of glioblastoma multiforme consists of debulking surgery followed by radio- and chemotherapy, as well as immunotherapy as adjuvant therapy, which cannot reduce the high rates of recurrence within a few months after treatment but only extend their overall survival. The response rates of already discovered chemotherapeutic agents were observed in the range of 0 to 20%, while radiotherapy remains the backbone of the treatment. However new treatment modalities must be developed for glioblastoma multiforme patients.

Glioblastoma Multiforme Treatment with RDC

• The Biomarker of Glioblastoma Multiforme
  Substance P, binding to the neurokinin type 1 receptor (NK-1), which is overexpressed in all gliomas regardless of the degree of malignancy is proven useful in glioblastoma multiforme treatment. Among a variety of radionuclides, neuronal toxicity can be best controlled by ultrashort range α emitters for brain tumor treatment, with less than 100 μm radioactive beam allowing selective irradiation of tumor cells.
• The Study of ²¹³Bi-DOTA-SP
  Combined radionuclide ²¹³Bi and Substance P, ²¹³Bi-DOTA-SP, the novel RDC (Radionuclide Drug Conjugate), is applied for glioblastoma multiforme treatment. After injecting ²¹³Bi-DOTA-SP, the uptake in the tumor area was increased as illustrated in a typical PET/CT image, while the whole-body scans presented a very low distribution in kidney and urine. The results demonstrate that ²¹³Bi-DOTA-SP was well tolerated with only mild transient adverse reactions and may evolve as a new option for the treatment of secondary glioblastoma multiforme.

Fig.1 PET/CT after local injection of a therapeutic dose of ²¹³Bi-DOTA-SP into the resection cavity of a glioblastoma in patient. (Krolicki, L., et al., 2018, Eur J Nucl Med Mol Imaging)

Reference

1. Krolicki, L., Bruchertseifer, F., Kunikowska, J., Koziara, H., Królicki, B., Jakuciński, M., ... & Morgenstern, A. (2018). Prolonged survival in secondary glioblastoma following local injection of targeted alpha therapy with ²¹³Bi-substance P analogue. European journal of nuclear medicine and molecular imaging, 45(9), 1636-1644.