Characterizing the biology of ACC by longitudinal dual-PET imaging and multi-omics analyses

Liang Zhang; Adam Edholm; Tobias AEkerstrom; Staffan Welin; Agnes Hegedus; Ieva Lase; Olov Norlen; Eir Lofgren; Britt Skogseid; Per Hellman; Anders Sundin; Joakim Crona

doi:10.1530/endoabs.107.009

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Endocrine Abstracts (2024) 107 009 | DOI: 10.1530/endoabs.107.009

IACS9 9th International Adrenal Cancer Symposium 2024 Abstracts (18 abstracts)

Characterizing the biology of ACC by longitudinal dual-PET imaging and multi-omics analyses

Liang Zhang ^1* , Adam Edholm ^1* , Tobias Ækerström ² , Staffan Welin ¹ , Agnes Hegedus ³ , Ieva Lase ¹ , Olov Norlén ² , Eir Löfgren ¹ , Britt Skogseid ¹ , Per Hellman ² , Anders Sundin ⁴ & Joakim Crona ¹

Author affiliations

*Shared authorship ¹Department of Medical Sciences, Uppsala University, Uppsala, Sweden ²Department of Endocrine Surgery, Uppsala University, Uppsala, Sweden ³Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden ⁴Department of Radiology & Molecular Imaging, Uppsala University, Uppsala, Sweden

Background: Adrenocortical Carcinoma (ACC) is a heterogenous disease characterized by variable degrees of adrenocortical differentiation and tumor growth rate: Both factors are important prognostic markers that are currently investigated on tumor tissue samples. As such we have a limited capacity to study ACC heterogeneity on the spatial level and to perform longitudinal measurements to document how ACC biology change over time. Molecular imaging may overcome these limitations with [¹⁸F]FDG uptake reflecting ACC metabolism while [¹⁸F]CETO is a new PET tracer targeting the adrenal cortex.

Aims: To study the use of dual-PET imaging as a mean to investigate ACC proliferation and adrenocortical differentiation over space and time.

Methods: A single-center prospective cohort study (PROGRESS ACC) that is aiming to include 20 patients with confirmed/suspected ACC before surgery or at disease recurrence/progression. Patients undergo PET/CT with [¹⁸F]FDG and [¹⁸F]CETO as well as collection of tumor tissue (surgery or biopsy) at study inclusion and at disease progression/recurrence. Tumor tissue is characterized by Whole genome sequencing and total-RNA sequencing with plasma samples undergoing targeted DNA sequencing.

Results: Four ACC patients have undergone dual-PET imaging and multi-omics characterization. The integrative analysis is ongoing: Two patients had tumors avid on both [¹⁸F]FDG and [¹⁸F]CETO imaging, while 2 patients had tumors avid on [¹⁸F]FDG-PET but with negligible [¹⁸F]CETO-uptake. The findings on PET-imaging could be validated in the gene expression dataset and by histopathology as shown in Table 1.

Table 1 with overview of results
Patient ID	Sample type	[¹⁸F]FDG PET SUV_max	[¹⁸F]CETO PET SUV_max	Ki-67 IHC	MKI67 RNA expression	CYP11B1 RNA expression
AC#1	Biopsy	21,2	26,9	38%	37.1	343.1
AC#2	Biopsy	10,7	171	8%	1.4	231.6
AC#3	Biopsy	29,3	4,12	25%	24.5	0.1
AC#4	Resection	12,8	3,2	10%	12.5	1.4
Legend: [¹⁸F]CETO, para-chloro-2-fluoroethyletomidate; [¹⁸F]FDG, Fluorodeoxyglucose; IHC, immunohistochemistry; PET, Positron emission tomography; SUVmax, maximum standardized uptake value.

Discussion: Dual-PET/CT imaging with [¹⁸F]FDG and [¹⁸F]CETO could be used to study ACC proliferation and differentiation in-vivo. Their combined use offers a unique potential for non-invasive analyses of ACC tumor biology. The PROGRESS-ACC study has so far included 9 ACC patients and the integrative analyses are ongoing.