{
  "abstract": "Background [ 18F]GEH200521, a novel CD8-targeted VHH nanobody PET tracer, has been developed as a potential same-day imaging biomarker for visualizing whole-body CD8+ T cell distribution. Visualization of CD8+ T cell distribution may support evaluation of therapy mechanism of action and identification of response to cancer therapy. We present results from two phase 1 studies sponsored by GE Healthcare, GE-269-001 (NCT05629689) and GE-269-004 (NCT06398730).Methods The GE-269-001 study enrolled 13 patients with solid tumors, and the GE-269-004 study enrolled six healthy volunteers. [ 18F]GEH200521 (radiolabeled IMP) was administered with a fixed dose of 110 or 185 MBq, for a long or shorter axial field-of-view PET scanner, respectively. GEH200520 (corresponding non-radioactive IMP) was co-administered at a protein mass dose of 1, 2, 4, or 8 mg. Subjects were imaged from the time of injection up to 5 h post-injection. Assessments were made for safety, tolerability, pharmacokinetics, immunogenicity, and [18F]GEH200521 uptake characteristics and dosimetry. Image analysis and dosimetry were performed using MIM and Olinda/EXM software.Results At all doses of GEH200520, [ 18F]GEH200521 was renally cleared, largely within the first 60 minutes post-injection. There was rapid uptake into CD8-rich tissues, minimal residual uptake in other tissues, and similar biodistribution and clearance across patients and healthy volunteers. There was also rapid uptake into tumor lesions (identified on diagnostic CT), with heterogeneous uptake observed in larger tumor lesions. Uptake into highly perfused lymphoid tissues (e.g., spleen and marrow) was reduced with increasing mass dose. PK and imaging results indicate that CD8 receptors were reaching saturation by 4 mg. Example images at 2 mg mass dose are shown in figure 1, with time activity curves across all mass doses shown in figure 2. The average whole-body effective dose across 2 mg mass dose subjects was 0.029 mSv/MBq. No serious adverse safety events or anti-drug antibodies were observed.Conclusions [ 18F]GEH200521, a 18F CD8 PET radiotracer, is a potential imaging biomarker to identify CD8+ cell biodistribution and guide therapeutic drug development and treatment decisions in patients. Preliminary data from both studies indicate that both GEH200520 and [18F]GEH200521 are safe and well-tolerated. [18F]GEH200521 offers same-day imaging within one-hour post-injection and a total-body effective dose similar to other F18-based tracers, enabling repeat imaging sessions. The 2 mg mass dose of GEH200520 was selected for Part B of both studies, where GE-269-001 will evaluate CD8 PET/CT imaging before and after two cycles of immune checkpoint inhibitor therapy, and GE-269-004 will evaluate test-retest reliability.Trial Registration ClinicalTrials.gov NCT05629689 ClinicalTrials.gov NCT06398730Ethics Approval The studies were approved by the University Medical Center Groningen’s and Vanderbilt University’s Ethics Boards, approval numbers METc 2022/187 and 240042, respectively. All subjects gave informed consent before participating in the studies.Abstract 104 Figure 1Whole-body maximum intensity projection images. Example MIP images at 2 mg GEH200520 and 60 min post-injection. (a-b) normal uptake biodistribution (b) retro-peritoneal metastasis and two reactive lymph nodes showing CD8 uptake but not suspected of metastases on other imaging modalitiesAbstract 104 Figure 2Time activity curves. Fast kinetics for same-day imaging: (a) clearance of blood pool. (b-c) uptake in highly-perfused lymphoid tissue decreases with increasing mass dose. (d-f) uptake in target tissues. Data corresponds to subjects in figure 1",
  "authors": [
    {
      "affiliations": [
        "GE HealthCare, Arlington Heights, IL, USA"
      ],
      "name": "Kristen A Wangerin"
    },
    {
      "affiliations": [
        "GE HealthCare, Pollards Wood, UK"
      ],
      "name": "Yaron Raiter"
    },
    {
      "affiliations": [
        "University Medical Center Groningen, Groningen, Netherlands"
      ],
      "name": "Adrienne H Brouwers"
    },
    {
      "affiliations": [
        "Vanderbilt University Medical Center, Nashville, TN, USA"
      ],
      "name": "Todd E Peterson"
    },
    {
      "affiliations": [
        "Vanderbilt University Medical Center, Nashville, TN, USA"
      ],
      "name": "Gary T Smith"
    },
    {
      "affiliations": [
        "University Medical Center Groningen, Groningen, Netherlands"
      ],
      "name": "Elisabeth GE de Vries"
    },
    {
      "affiliations": [
        "University Medical Center Groningen, Groningen, Netherlands"
      ],
      "name": "Erik FJ de Vries"
    },
    {
      "affiliations": [
        "University Medical Center Groningen, Groningen, Netherlands"
      ],
      "name": "Derk JA de Groot"
    },
    {
      "affiliations": [
        "Vanderbilt University Medical Center, Nashville, TN, USA"
      ],
      "name": "Adam J Rosenberg"
    }
  ],
  "title": "104 Evaluation of whole body CD8+ T cell distribution using an 18F-labeled PET tracer: phase 1 studies in patients with solid tumors and healthy volunteers",
  "uid": "cc877ad7-9675-53f5-a418-24f9d20b696b"
}