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NCT Number: NCT05255926

CXCR4-targeted PET/CT Imaging in Hematological Malignancies

Hematological malignancies continue to pose significant clinical challenges due to their high incidence, heterogeneous biology, and substantial mortality. Although 18F-FDG PET/CT remains the most commonly used molecular imaging modality, its limited specificity can result in false-positive or false-negative findings, especially in indolent or low-metabolism subtypes, thereby hampering accurate diagnosis, staging, and therapeutic evaluation. C-X-C chemokine receptor type 4 (CXCR4) is frequently overexpressed in a broad spectrum of hematologic malignancies and correlates with aggressive disease and unfavorable outcomes. CXCR4-targeted molecular imaging using ^68Ga-pentixafor PET/CT has shown promise for improved disease characterization. This prospective study aims to systematically compare 68Ga-pentixafor PET/CT with 18F-FDG PET/CT in terms of diagnostic performance, staging accuracy, risk stratification, and prognostic relevance in patients with hematological malignancies. Furthermore, the study will incorporate artificial intelligence-based image analysis to enhance lesion detection, automate quantitative assessments, and support personalized clinical decision-making.

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Key information

Age range

18 year–90 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Zhongnan Hospital of Wuhan University

Wuhan, Hubei, 430071, China

Location status: Recruiting

Location contact

Lei Zheng

CONTACT

+86-27-67812787

Yong He, MD, PhD

PRINCIPAL_INVESTIGATOR

About this study

Hematological malignancies encompass a heterogeneous group of neoplasms originating from the bone marrow and lymphatic system. Despite advances in therapeutic strategies, the prognosis for many subtypes remains suboptimal, and accurate initial evaluation is critical for appropriate treatment planning. ^18F-FDG PET/CT is routinely used for functional imaging in these patients; however, its diagnostic utility is limited by variable glucose metabolism across disease subtypes and inflammatory uptake, which can lead to misclassification.

CXCR4, a chemokine receptor involved in tumor proliferation, invasion, and microenvironmental interactions, is overexpressed in numerous hematologic malignancies and has emerged as a molecular target for both imaging and therapy. 68Ga-pentixafor, a CXCR4-targeted PET radiotracer, has demonstrated superior lesion detection in preliminary studies, particularly in diseases with low 18F-FDG avidity.

This prospective study will investigate the clinical utility of 68Ga-pentixafor PET/CT in patients with newly diagnosed or relapsed hematological malignancies. Comparative analyses with 18F-FDG PET/CT will be performed to assess concordance, staging accuracy, and association with known risk stratification systems. Longitudinal follow-up will be conducted to evaluate the prognostic relevance of imaging findings.

In parallel, the study will explore the application of artificial intelligence (AI) techniques, including deep learning-based image segmentation and radiomic feature extraction, to enhance diagnostic precision and support risk-adapted management strategies. AI-driven models will be developed and validated to predict disease burden, progression, and survival, thereby contributing to personalized medicine in hematologic oncology.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Volunteer to participate and sign an informed consent form;
  • 18 ≤ Age ≤ 90 years;
  • Patients with highly suspected, or newly diagnosed, or relapsed hematological malignancies;
  • Willing and able to follow schedule visits, treatment plans and laboratory tests.

Exclusion criteria

  • pregnancy or breastfeeding;
  • Allergic to CXCR4-targeted tracers or excipients;
  • Fasting blood glucose level exceeded 11.0 mmol/L prior to injection of 18F-FDG;
  • Those who cannot complete PET/CT scan, including inability to keep supine, claustrophobia, radiation phobia, etc.;
  • Researchers think it is inappropriate to participate in this clinical trial for patients with poor compliance or other unsuitable factors.

Treatment and study plan

68Ga-Pentixafor

Drug

All participants undergo intravenous administration of 68Ga-pentixafor (1.85-3.71 MBq/kg body weight).

PET/CT

Device

PET/CT imaging is performed 1 h after intravenous injection of 68Ga-pentixafor.

Other names: Positron Emission Tomography/Computed Tomography

Primary outcomes

  1. Diagnostic Accuracy of 68Ga-pentixafor PET/CT Compared to 18F-FDG PET/CT in Hematological Malignancies

    Time frame: Two years

    To assess and compare the diagnostic accuracy of 68Ga-pentixafor PET/CT and 18F-FDG PET/CT in patients with newly diagnosed, relapsed, or highly suspected hematological malignancies. Accuracy will be evaluated using a composite reference standard, including histopathological confirmation, clinical follow-up, and additional imaging findings.

  2. Concordance of [⁶⁸Ga]Ga-pentixafor PET/CT with Standard Clinical Staging Systems

    Time frame: Two years

    To evaluate the concordance between [⁶⁸Ga]Ga-pentixafor PET/CT-based staging and conventional clinical staging systems (e.g., Ann Arbor, Durie-Salmon PLUS, R-ISS/R2-ISS) in patients with hematological malignancies. Concordance will be measured using Cohen's kappa statistic (κ).

  3. Predictive Value of [⁶⁸Ga]Ga-pentixafor PET/CT Parameters for Progression-Free Survival

    Time frame: Four years

    To assess whether imaging biomarkers from [⁶⁸Ga]Ga-pentixafor PET/CT, such as SUVmax or total lesion CXCR4 uptake, predict progression-free survival (PFS) in patients with hematological malignancies. Comparison will be made with [¹⁸F]FDG PET/CT-derived parameters.

  4. Predictive Value of [⁶⁸Ga]Ga-pentixafor PET/CT Parameters for Overall Survival

    Time frame: Four years

    To evaluate whether [⁶⁸Ga]Ga-pentixafor PET/CT-based biomarkers can predict overall survival in patients with hematological malignancies, compared with [¹⁸F]FDG PET/CT.

  5. Dice Similarity Coefficient (DSC) for AI-based lesion segmentation

    Time frame: Two years

    Evaluation of the overlap between artificial intelligence-generated lesion segmentations and expert manual annotations on PET/CT images using the Dice similarity coefficient (DSC).

Secondary outcomes

  1. Correlation Between CXCR4 Expression and [⁶⁸Ga]Ga-pentixafor PET/CT Parameters

    Time frame: Two years

    To assess the correlation between CXCR4 expression levels in biopsy samples and semiquantitative parameters from [⁶⁸Ga]Ga-pentixafor PET/CT (e.g., SUVmax).

  2. Correlation between del(17p) status and TLU on [68Ga]Ga-pentixafor PET/CT

    Time frame: Two years

    To assess the correlation between the presence or absence of del(17p), as identified by fluorescence in situ hybridization (FISH), and total lesion uptake (TLU) on [68Ga]Ga-pentixafor PET/CT at baseline. The degree of correlation will be measured using the Spearman correlation coefficient (rho), a unitless value ranging from -1 to +1.

  3. Radiogenomic Model for Risk Prediction Using AI

    Time frame: Two years

    To develop and validate an AI-based radiogenomic model integrating PET imaging features and genomic data to predict disease aggressiveness in patients with hematological malignancies.

Study contacts

Contact information is provided by the study sponsor or research team.

Yong He, MD, PhD

CONTACT

[email protected]

+86-27-67812698

Sponsors and collaborators

Lead sponsor

Zhongnan Hospital

Other

Registry information

Official study title

An Exploratory, Open-Label, Single Center Study of CXCR4-targeted PET/CT Imaging for Evaluation of Hematological Malignancies

Important dates

Study start
2022
Primary completion
2026
Study completion
2026
First posted
Feb 25, 2022
Registry last updated
Jun 26, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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