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Endocrine

Endocrine/Head & Neck Poster Presentations 1

P24: Novel PARP-1 PET/CT imaging in Pheochromocytoma and Paraganglioma

Thursday, March 21, 2024
9:42am – 9:48am ET
Location: C108

    Oral Poster Presenter(s)

  • Heather Wachtel, MD (she/her/hers)

    Associate Professor of Surgery
    Department of Surgery, Hospital of the University of Pennsylvania
    Philadelphia, Pennsylvania, United States

    • Submitter(s)

  • Heather Wachtel, MD (she/her/hers)

    Associate Professor of Surgery
    Department of Surgery, Hospital of the University of Pennsylvania
    Philadelphia, Pennsylvania, United States

    • Author(s)

  • Heather Wachtel, MD (she/her/hers)

    Associate Professor of Surgery
    Department of Surgery, Hospital of the University of Pennsylvania
    Philadelphia, Pennsylvania, United States

  • AP

    Austin Pantel, MD

    Assistant Professor of Radiology, Division of Nuclear Medicine and Clinical Molecular Imaging
    Hospital of the University of Pennsylvania, United States

  • MB

    Maria Bonanni, CRNP

    Nurse Practitioner Medical Genetics
    Hospital of the University of Pennsylvania, United States

  • BB

    Bonita Bennett, RN

    Neuroendocrine Tumor Program
    Hospital of the University of Pennsylvania, United States

  • DC

    Debbie L. Cohen, MD

    Professor of Medicine, Division of Renal-Electrolyte and Hypertension
    Hospital of the University of Pennsylvania, United States

  • Jennifer Eads, MD (she/her/hers)

    Associate Professor of Clinical Medicine, Hematology/Oncology
    Hospital of the University of Pennsylvania, United States

  • VN

    Vivek Narayan, MD MS

    Assistant Professor of Medicine, Hematology/Oncology
    Hospital of the University of Pennsylvania, United States

  • KN

    Katherine Nathanson, MD

    Professor of Medicine, in the Division of Translational Medicine and Human Genetics
    Hospital of the University of Pennsylvania, United States

  • DP

    Daniel Pryma, MD

    Professor of Radiology, Division of Nuclear Medicine and Clinical Molecular Imaging
    Hospital of the University of Pennsylvania, United States

Disclosure(s):
Heather Wachtel, MD: No financial relationships to disclose
Introduction: Pheochromocytoma (PCC) and paraganglioma (PGL) are neuroendocrine tumors caused by hereditary predisposition genes in ~40% of cases. Germline pathogenic variants in succinate dehydrogenase genes (SDHx) are risk factors for aggressive disease, and treatment options are limited. Recent investigations suggest that SDHx-deficient PCC/PGL may be susceptible to treatment with PARP-1 inhibitors. The goal of this study was to use a novel PARP-1 PET/CT technique to assess potential PARP-1 inhibitor susceptibility in patients with PCC/PGL.


Methods: Patients with PCC/PGL were prospectively enrolled (NCT05636540). 18F-FluorThanatrace (FTT) was imaged on the long axial field-of-view PennPET Explorer PET/CT with 60 minutes of dynamic head-to-thigh scanning (single bed position), with a second scan performed 90 minutes post-injection. Adverse events were assessed. The primary outcome was SUVmax, which was assessed with respect to demographic and clinical characteristics. Metastatic disease was defined as the presence of PCC/PGL in non-chromaffin derived tissues. Clinical genetic testing was performed for known PCC/PGL hereditary predisposition genes.


Results: Of the initial 5 subjects (bearing 12 assessable tumors—6 PCC and 6 PGL), mean age was 51 years and 4 subjects were female. Two subjects had metastatic disease. Five tumors were SDHB-associated, 5 had no known predisposition genes, and 2 tumors had pending germline testing. All tumors demonstrated FTT uptake, with a median SUVmax of 3.8 (IQR 3.1-8.7). Median SUVmax was significantly higher in PGL (8.7) compared to PCC (3.1, p=0.004). SUVmax was not significantly associated with metastatic status (p=0.309). Median SUVmax was highest in SDHx-associated tumors (9.7, IQR 7.6-10.4) as shown in Fig. 1, compared to tumors with no known predisposition genes (2.8, IQR 1.9-3.4) and those with pending germline genetic testing (3.7, IQR 3.3-4, p=0.014). No adverse events grade 2 or higher were observed.


Conclusions: This is the first report of PARP-1 PET/CT imaging in PCC/PGL. PARP-1 PET/CT is safe and well-tolerated. FTT uptake appears to correlate with PGLs and SDHB germline pathogenic variants, supporting that these tumors may be susceptible to treatment with PARP-1 inhibitors.

Learning Objectives:

  • describe the rationale for FTT PET/CT in PARP-1 susceptible tumors.
  • describe the correlation between SDHx variants and PARP-1 inhibition.
  • describe the conduct of FTT PET/CT.