68Ga-DOTA.SA.FAPI as a Potential, Noninvasive Diagnostic Probe for Recurrent and Metastatic Adrenocortical Carcinoma A Head-to-Head Comparison With 18F-FDG

Sejal Chopra, MSc,* Rama Walia, MD,¡ Yamini Mathur, MD, DNB,* Frank Roesch, PhD,± Euy Sung Moon, PhD,¿ Nivedita Rana, PhD,* Somit Pandey, MSc,* Debajyoti Chatterji, DM,§ Rajender Kumar, MD,* Harmandeep Singh, MD,* Bhagwant Rai Mittal, MD, DNB,* and Jaya Shukla, PhD*

Abstract: Metastatic or recurrent adrenocortical carcinoma (ACC) is a po- tentially fatal malignancy, which poses major challenges in disease manage- ment owing to lack of effective systemic therapies. The drastically reduced survival rates require prompt identification of selective molecules for devel- opment of targeted therapeutics. We evaluated the squaric acid containing FAPI derivative, DOTA.SA.FAPI (FAPI), as a potential diagnostic probe in 2 cases of histopathologically proven metastatic and recurrent ACC. Both patients underwent 18F-FDG and 68Ga-FAPI PET/CT scans for comparative analysis. 68Ga-DOTA.SA.FAPI emerged as an excellent diagnostic agent for ACC and performed similar to 18F-FDG.

Key Words: 18F-FDG, 68Ga-DOTA.SA.FAPI, PET/CT, adrenocortical carcinoma

(Clin Nucl Med 2023;48: e173-e175)

Received for publication July 24, 2022; revision accepted November 14, 2022. From the *Department of Nuclear Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India; ¡ Department of Endocrinology, Postgraduate Institute of Medical Education and Research, Chandigarh, India; ¿ Department of Chemistry, Johannes Gutenberg University, Mainz, Germany; and §Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India

Conflicts of interest and sources of funding: none declared.

Correspondence to: Jaya Shukla, PhD, Department of Nuclear Medicine, Postgraduate Institute of Medical Education and Research, Sector-12, Chandigarh 160012, India. E-mail: shuklajaya@gmail.com.

DOI: 10.1097/RLU.0000000000004563

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FIGURE 1. Histopathological images showing (A) trabecular pattern of growth in patient 1 (hematoxylin-eosin, x100) and (B) large areas of necrosis in patient 2 (hematoxylin-eosin, x100).

FIGURE 2. A 39-year-old woman diagnosed with right adrenocortical carcinoma (ACC) (Fig. 1A) underwent adrenalectomy in 2017. For disease restaging, 18F-FDG scan was performed, which revealed metastatic disease with tracer-avid soft tissue lesions in bilateral lung fields and aortocaval lymph nodal metastases. Post 6 cycles of EDP-M chemotherapy, patient underwent 18F-FDG (281.2 MBq) and 68Ga-FAPI (111 MBq) PET/CT imaging on consecutive days for treatment response evaluation. The MIP images (G) of 68Ga-FAPI showed physiological tracer uptake in the brain, thyroid, salivary glands, liver, pancreas, muscles, and blood pool with excretion via kidneys and urinary bladder. The MIP (A and G), transaxial fused FDG PET/CT, transaxial CT, and transaxial fused FAPI PET/CT images (B-F) for both tracers demonstrated 13 lung lesions (largest in RUL; FDG vs FAPI SUVmax: 6.4 vs 16.6, B-D) along with para-aortic (SUVmax: 3.2 vs 2.3), aortocaval (SUVmax: 6.7 vs 3.6, E), and right inguinal (SUVmax: 1.0 vs 4.7) lymph nodal involvement. Moreover, 68Ga-FAPI identified an additional hepatic lesion, which was missed by 18F-FDG (SUVmax: 4.87, F). Nonspecific 18F-FDG tracer uptake was noted in dental caries and paravertebral muscles, which was absent on the 68Ga-FAPI scan.

F18-FDG

Ga68-FAPI

FIGURE 3. A 50-year-old woman underwent adrenalectomy for right ACC in 2016 (Fig. 1B). In 2020, contrast-enhanced CT showed heterogeneously enhancing lesion in the right adrenal region suggestive of recurrence. In 2021, 18F-FDG scan revealed metastatic disease peripheral enhancing lesion postlateral to the main lesion, lymph nodal mass in the hepatorenal space, along with metabolically active deposits in the right abdominal and lumbar region. Post 4 cycles of EDP-M chemotherapy, patient underwent 18F-FDG (296 MBq) and 68Ga-FAPI (118.4 MBq) PET/CT imaging on consecutive days for treatment response evaluation. The MIP images (A and F), transaxial fused FDG PET/CT, transaxial CT, and transaxial fused FAPI PET/CT images (B-E) for both tracers identified 7 lung lesions (FDG vs FAPI SUVmax: 2.4 vs 3.7), subcapsular liver deposit (SUVmax: 10.7 vs 9.9, B), ill-defined hypodense lesion in segment VI of right lobe of liver (SUVmax: 12.24 vs 18.08, C), heterogeneously enhancing ill-defined sheet like soft tissue mass in the postoperative bed (SUVmax: 10.4 vs 22.0, D), multiple subcutaneous deposits (SUVmax: 10.7 vs 16.17, E), peritoneal deposits (SUVmax: 10.7 vs 16.10, E), and aortocaval (SUVmax: 6.4 vs 5.6) lymph nodal involvement. The current treatment regimen for metastatic disease involves systemic therapy with mitotane alone or in combination with etoposide, doxorubicin, and cisplatin with a high incidence of toxicity.12 Hence, there is an urgent need for the identification of suitable molecular probes, which may act as steppingstones toward precision oncology.3-10 In this case series, 68Ga-DOTA.SA.FAPI emerged as an excellent diagnostic imaging probe for metastatic ACC by targeting the FAP-expressing cancer-associated fibroblasts (FAP+"CaFs). Moreover, the FAPI derivatives when labeled with 225Ac or 177Lu may pave the pathway toward the development of targeted therapeutics.

F18-FDG

Ga68-FAPI

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68Ga-DOTA.SA.FAPI as a Potential, Noninvasive Diagnostic Probe for Recurrent and Metastatic Adrenocortical Carcinoma A Head-to-Head Comparison With 18F-FDG

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