CXCR4 PET/MRI Targeted Imaging for Grading Diagnosis, Molecular Typing, and Prognostic Evaluation of Brain Glioma

Clinical Study on CXCR4 PET/MRI Targeted Integrated Imaging for Grading Diagnosis, Molecular Typing, and Prognostic Evaluation of Brain Glioma

This project intends to evaluate the role of C-X-C chemokine receptor type 4 (CXCR4) targeted PET/MRI integrated imaging in the grading and molecular typing of brain gliomas, using primary glioma patients as the research subjects and post-operative histopathological analysis as the reference, and to establish an evaluation model for the prognosis of primary glioma patients.

Study Overview

• Status: Recruiting
• Conditions: Glioma
• Intervention / Treatment: Diagnostic test: CXCR4

Detailed Description

1. PET/MRI Scan: Image acquisition was completed 15 days before surgery. CXCR4 contrast agent was injected at 6.5 MBq/kg based on body mass, with no drug extravasation, and imaging was performed after 60 minutes of quiet rest. All subjects were scanned in a supine position on a single bed of the Signa™ 3.0T scanner (GE Healthcare Systems), using a 3.0T gem HNU head coil with a scanning field of view focused on the head. PET acquisition lasted for 20 minutes and was reconstructed using OSEM. Simultaneous MRI acquisition included MR-based attenuation correction (MRAC) - zero echo time pulse sequence (ZTE), as well as structural and functional MRI sequences (T1WI, T2WI, FLAIR, DWI, MRS, DSC, T1-CE). Image fusion was performed on a GE post-processing workstation.
2. Image Analysis and Observation Indicators: PET/MRI images were independently reviewed and processed by two experienced neuroradiologists. Using IKT-SNAP software, target lesion VOIs were outlined based on FLAIR and T1-CE sequences. VOI delineation on the FLAIR sequence included solid tumor components, necrotic areas, and surrounding abnormal FLAIR signal regions. VOI delineation on the T1-CE sequence included enhanced solid components, non-enhanced solid components, and necrotic areas. MRI parameters (diffusion-weighted imaging parameters: ADC; perfusion imaging parameters: CBF, CBV, MTT, TTP; spectroscopic parameters: NAA, Cho, Cr, Lac, NAA/Cr, Cho/Cr) and PET parameters (SUVmax, SUVmean, SUVpeak, CXCR4 metabolic volume, TBR) were measured throughout the tumor and corresponding regions.
3. Pathological Analysis: Slices containing no less than 25% tumor tissue were used, with each slice having a thickness of 4um. HE, CD34, and CXCR4 immunohistochemical staining were performed separately. Two senior pathologists reviewed the slides using a double-blind method. IDH mutation status and 1p/19q deletion status were determined by the pathology department.

• Study Type: Observational
• Enrollment (Estimated): 60

Contacts and Locations

• Study Contact: Name: Du ZHenwei, Ph.D; Phone Number: +8618580503880; Email: peter11dzw@126.com

Study Locations

• China
  • Chongqing
    • Chongqing, Chongqing, China, 400000
      • Recruiting
      • Department of Nuclear Medicine, Daping Hospital of Army Medical University
      • Contact: Chen Xiao; Phone Number: +8615922970174; Email: xiaochen229@foxmail.com
      • Contact: Du Zhenwei; Phone Number: +8618580503880; Email: peter11dzw@126.com
      • Principal Investigator: Chen Xiao
      • Sub-Investigator: Du Zhenwei

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

The subjects are adults with newly diagnosed primary glioma, regardless of gender.

Description

Inclusion Criteria:

1. Patients diagnosed with primary glioma based on clinical, imaging, and histopathological criteria;
2. The patient is at least 18 years old;
3. Participate in CXCR4 PET/MRI imaging within 15 days before surgery;
4. Surgical resection of glioma lesion tissue can be used for pathological analysis;
5. The patient voluntarily participates and signs the informed consent form.

Exclusion Criteria:

1. Pregnant or breastfeeding patients;
2. The image quality of the imaging is poor and cannot be used for diagnosis and evaluation;
3. Molecular typing was not determined by histologic examination;
4. patients with claustrophobia;
5. Patients who are allergic to radioactive tracers and MRI contrast agents, and patients with renal insufficiency.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Standardised uptake values	Standardised uptake values of suspected glioma disease in CXCR4 PET/MRI imaging	completed within one week after the PET/MRI examination
expression of CD34	Immunohistochemical evaluation of the expression of CD34 in postoperative tumor tissue	completed within one week after surgery
expression of CXCR4	Immunohistochemical evaluation of the expression of CXCR4 in postoperative tumor tissue	completed within one week after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SUV and histological grading of glioma	Correlation between SUV and histological grading of glioma	through study completion, an average of 1 year
CXCR4 expression and histological grading of glioma	Correlation between CXCR4 expression and histological grading of glioma	through study completion, an average of 1 year
SUV and IDH mutation status	Correlation between SUV and IDH mutation status	through study completion, an average of 1 year
SUV and 1p/19q deletion status	Correlation between SUV and 1p/19q deletion status	through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Xiao Chen
• Investigators: Principal Investigator: Chen Xiao, Ph.D, Daping Hospital, Army Medical University

Publications and helpful links

General Publications

• Jacobs SM, Wesseling P, de Keizer B, Tolboom N, Ververs FFT, Krijger GC, Westerman BA, Snijders TJ, Robe PA, van der Kolk AG. CXCR4 expression in glioblastoma tissue and the potential for PET imaging and treatment with [68Ga]Ga-Pentixafor /[177Lu]Lu-Pentixather. Eur J Nucl Med Mol Imaging. 2022 Jan;49(2):481-491. doi: 10.1007/s00259-021-05196-4. Epub 2021 Feb 7.

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2024
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: January 4, 2024
• First Submitted That Met QC Criteria: January 29, 2024
• First Posted (Actual): January 31, 2024

Study Record Updates

• Last Update Posted (Estimated): March 5, 2024
• Last Update Submitted That Met QC Criteria: March 3, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioma
• Other Study ID Numbers: 20230294

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No