68Ga-PFD3 PET Imaging for the Diagnosis and Evaluation of Small Cell Lung Cancer

March 27, 2026 updated by: Tingting Yuan, Peking University First Hospital

Targeting Delta-like Ligand 3 (DLL3) With 68Ga-PFD3 PET/CT for the Diagnosis and Assessment of Small Cell Lung Cancer (SCLC)

This study aims to investigate and evaluate the safety and performance of a novel probe, PFD3, for the diagnosis and assessment of patients with small cell lung cancer (SCLC).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Small cell lung cancer (SCLC) constitutes approximately 15% of all lung cancers and is characterized by its aggressive biology, rapid growth, and early, widespread metastasis. It is highly lethal, with a 5-year survival rate of less than 7% for patients with extensive-stage disease. The current standard of care relies on the clinical staging of patients as either limited-stage (LS-SCLC) or extensive-stage (ES-SCLC), which fundamentally dictates therapeutic strategies. LS-SCLC, where disease is confined to a single radiation port, is potentially curable with concurrent chemoradiotherapy. Conversely, ES-SCLC, with metastases beyond a single radiation field, is treated primarily with systemic chemotherapy. Accurate staging is therefore critical for optimal patient management.

[18F]-FDG PET/CT is a cornerstone for staging SCLC due to its high sensitivity in detecting metabolically active tumor sites, including occult metastases. This capability has significantly improved the accuracy of distinguishing LS-SCLC from ES-SCLC, thereby guiding appropriate use of definitive radiotherapy. However, the clinical utility of [18F]-FDG-PET/CT is hampered by its suboptimal specificity. FDG avidity is common in inflammatory processes and other malignancies, leading to false-positive interpretations, particularly in lymph nodes. This limitation can result in overstaging, causing a subset of patients with truly limited-stage disease to be incorrectly classified as extensive-stage. Consequently, these patients may be denied potentially curative radiotherapy and receive only palliative chemotherapy, representing a significant missed therapeutic opportunity. There is a clear unmet need for a more specific imaging agent for SCLC.

Delta-like ligand 3 (DLL3) is a cell-surface protein that is rarely expressed in healthy adult tissues but is overexpressed in over 80% of SCLC cases, as well as in other high-grade neuroendocrine tumors (e.g., neuroendocrine prostate cancer, neuroendocrine tumors of the gastrointestinal tract). Its highly restricted expression profile makes DLL3 an exceptionally promising target for both diagnosis and therapy. Several DLL3-targeted therapeutic agents, such as antibody-drug conjugates (e.g., rovalpituzumab tesirine) and bispecific T-cell engagers, are in development or clinical trials. Therefore, an imaging probe for detecting DLL3 expression could not only aid in diagnosis and staging but also serve as a biomarker to select patients most likely to benefit from these targeted therapies-a concept known as patient stratification for theranostics.

To translate this target into imaging, the probe must have favorable pharmacokinetics. Nanobodies, derived from camelid single-domain antibodies, are approximately 15 kDa in size, significantly smaller than conventional monoclonal antibodies (~150 kDa). This small size confers several advantages for imaging: superior tissue penetration, rapid clearance from the bloodstream, and reduced immunogenicity. PFD3 is a novel probe constructed by conjugating a DLL3-specific nanobody with a chelator for 68Ga radiolabeling. This design offers dual advantages: first, the high affinity and specificity of the nanobody for DLL3 ensure targeted accumulation in tumors, minimizing off-target binding. Second, the nanobody's pharmacokinetics result in a shorter in vivo residence time compared to monoclonal antibody-based probes, enabling same-day imaging protocols with enhanced patient convenience and potentially improved safety profiles due to more predictable radiopharmaceutical retention. Furthermore, the growing pipeline of DLL3-directed therapeutics makes the development of an accompanying diagnostic tool like PFD3 clinically relevant for both patient selection and treatment monitoring.

Given this background, this study aims to evaluate the safety and imaging performance of [68Ga]Ga-PFD3 PET/CT in human subjects with SCLC. Furthermore, a head-to-head comparison between [68Ga]Ga-PFD3 PET/CT and the widely used [18F]-FDG PET/CT will be conducted to determine the relative diagnostic performance of this novel, target-specific tracer.

Study Type

Interventional

Enrollment (Estimated)

30

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Tingting Yuan, M. D.
  • Phone Number: +86-13051707479
  • Email: biluohtt@163.com

Study Locations

  • China
    • Beijing Municipality
      • Beijing, Beijing Municipality, China, 100034
        • Recruiting
        • Peking university first hospital nuclear medicine
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Adults.
  • Histologically confirmed small cell lung cancer (SCLC).
  • At least one measurable lesion ≥1 cm in diameter (primary tumor, metastatic lesion, or involved lymph node) confirmed by standard imaging modalities.
  • Laboratory tests (complete blood count and biochemical analysis) completed within 4 weeks prior to enrollment.

Exclusion Criteria:

  • Pregnancy.
  • Breastfeeding.
  • Acute psychiatric disorders.
  • Inability to undergo PET scanning (e.g., due to claustrophobia, weight limits, or other medical contraindications).
  • Inability to complete the study procedures as anticipated.
  • Prior therapy targeting DLL3.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Eligible participants
Sequential [18F]-FDG PET/CT and [68Ga]Ga-PFD3 PET/CT
Diagnostic test: Sequential [18F]-FDG PET/CT
Based on individual clinical circumstances, eligible patients will undergo sequential [18F]FDG PET/CT and [68Ga]Ga-PFD3 PET/CT scans within one week.
Diagnostic test: [68Ga]Ga-PFD3 PET/CT scan
Based on individual clinical circumstances, eligible patients will undergo sequential [18F]FDG PET/CT and [68Ga]Ga-PFD3 PET/CT scans within one week.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse events (assessed using CTCAE grades)
Time Frame: 1 week after injection
Post-injection, patients will be assessed for treatment-related adverse events at 24 hours and within one week, using CTCAE grades. The [68Ga]Ga-PFD3 PET/CT will be considered safe if no possible or confirmed, Grade 3 or higher adverse events are identified.
1 week after injection
Correlation between PFD3 uptake and DLL3 expression
Time Frame: Baseline
Quantitative assessment of DLL3 expression in patient biopsy lesions using immunohistochemistry will be correlated with uptake parameters from [68Ga]Ga-PFD3 PET/CT scans.
Baseline

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Imaging performance of [68Ga]Ga-PFD3 PET/CT
Time Frame: Baseline
Including sensitivity, specificity, and other diagnostic metrics, in a head-to-head comparison with FDG.
Baseline
Progression-free survival
Time Frame: From baseline PET/CT imaging to disease progression or death, assessed up to 12 months post-imaging
Progression-free survival (PFS) is defined as the time from the date of baseline [68Ga]Ga-PFD3 PET/CT imaging to the date of first documented disease progression or death from any cause, whichever occurs first.
From baseline PET/CT imaging to disease progression or death, assessed up to 12 months post-imaging
Overall Survival
Time Frame: Through study completion, an average of 13 months
Overall survival (OS) is defined as the time from the date of baseline PET/CT imaging to the date of death from any cause. Patients who are alive at the time of analysis will be censored at their last known alive date.
Through study completion, an average of 13 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Peking University First Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 1, 2025

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

December 31, 2027

Study Registration Dates

First Submitted

March 21, 2026

First Submitted That Met QC Criteria

March 27, 2026

First Posted (Actual)

April 2, 2026

Study Record Updates

Last Update Posted (Actual)

April 2, 2026

Last Update Submitted That Met QC Criteria

March 27, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2025-6-PFD3

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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