Immuno-Positron Emission Tomography (PET)-Glioma Study, a Proof-of-principle Imaging Study

NCT ID: NCT05753995

Last Updated: 2025-04-01

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-03-01
• Study Completion Date: 2026-12-01

Brief Summary

Imaging of proinflammatory activated microglia by Purine 2X7 (P2X7) receptor scintigraphy in Positron Emission Tomography (PET) scanner in Glioblastoma patients.

Detailed Description

Glioblastomas are extremely malignant tumors of the brain; despite different therapeutic approaches, the median survival is only about 1 ½ years. This makes the need for action to investigate the mechanisms of action of new drug approaches all the more urgent. In the therapy of malignant intracerebral neoplasms, immunological processes between tumor and endogenous immune response represent a key phenomenon for understanding response.

In the CheckMate-143 trial, an anti-programmed cell death-1 monoclonal antibody disappointed by ineffectiveness in the vast majority of Glioblastoma patients (although a minority benefited significantly). This will be largely explained by the immunological milieu of the tumor. One-third of the cells in Glioblastoma constitute the microglia or monocyte cell population. These immunocompetent cells also serve as a protective shield for the Glioblastoma against a possible therapy-induced endogenous immune response.

Corresponding research is being conducted preclinically on cell cultures, brain tissue samples (immunohistochemistry, autoradiography) and in animal models. A major role is played by microglial cells, which perform the immunocompetent function in the brain. Microglia and monocytes have an activation state as well as an opposite of a suppressive one in their immunological function. This M1 or M2 concept is similar to the old postulated Th1 or Th2 principle in lymphocytes. Different purinergic receptors -P2Y12R and Purine receptor 2XR - are active here, respectively. Recently, antibody-based positron-emitter-labeled tracers have been developed for this purpose and thus, in principle, positron emission tomography (PET) imaging in vivo is possible.

The subsequent clinical relevance of a better understanding of these processes would consist in a combined therapeutic concept, in which additionally an immunomodulation in the desired direction of the regional activity of the immunocompetent cells could take place.

Methods for in vivo imaging of activated microglia in positron emission computed tomography scanners (PET) have already been developed - e.g. translocator protein positron emission tomography (TSPO-PET) by detecting mitochondrial activation of microglial cells. Here, however, it is not possible to distinguish between pro- and anti-inflammatory function of the immunocompetent cells. However, it is possible to do so by specific receptor recognition. For example, the purinergic receptor P2X7 is only expressed during proinflammatory activity. For this purpose, the positron emission tomography scanners (PET) tracer [18-Fluorine] Johnson & Johnson (JNJ)-64413739 has been developed in the academic research field. Patient cohort studies are still pending in this regard. Our intention is to investigate in patients with untreated Glioblastoma whether effective imaging of immunological disease activity is possible in this way.

Conditions

Glioblastoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

single arm

for diagnostic

Group Type: OTHER

PET imaging

Intervention Type: DIAGNOSTIC_TEST

The evaluation of PET imaging using PET ligand \[18F\]JNJ-64413739 or a \[18F\] labeled equivalent in vivo in patients.

Interventions

PET imaging

The evaluation of PET imaging using PET ligand \[18F\]JNJ-64413739 or a \[18F\] labeled equivalent in vivo in patients.

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• Patients with a new probable diagnosis of glioblastoma based on MRI imaging.
• prior to initiation of specific tumor therapy and prior to any surgery (including biopsy)
• short-term medication for cerebral edema (including corticosteroids) and short-term administration of antiepileptic drugs are not a reason for exclusion

Exclusion Criteria

• Non-business capacity
• Pregnancy
• breastfeeding period
• Other malignant disease (active)
• Concurrent participation in another clinical trial
• Foreseeable compliance problems

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Kepler University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Robert Pichler, PD, MD

Role: PRINCIPAL_INVESTIGATOR

Kepler University Hospital

Locations

Kepler University Hospital

Linz, Upper Austria, Austria

Countries

Austria

Other Identifiers

Immuno-PET-Glioma study

Identifier Type: -

Identifier Source: org_study_id