29578871

Prostate-Specific Membrane Antigen Expression in Adrenocortical Carcinoma on 68Ga-Prostate-Specific Membrane Antigen PET/CT

Saurabh Arora, MD,* Nishikant Avinash Damle, MD, DNB,* Sameer Aggarwal, DM,; Averilicia Passah, MD,* Abhishek Behera, MD,* Geetanjali Arora, PhD,* Chandrasekhar Bal, MD,* and Madhavi Tripathi, MD*

Abstract: We present here a case of metastatic adrenocortical carcinoma with bilateral lung nodules. The patient had been treated with mitotane therapy initially and then was later referred for chemotherapy. There was progression of disease noted on the 18F-FDG PET/CT. 68Ga prostate-specific membrane antigen (PSMA) PET/CT was planned to explore the possibility of future treatment with 177Lu-DKFZ-PSMA-617. It revealed peripheral increased uptake of 68Ga-HBED-CC-PSMA equal to liver uptake.

Key Words: adrenocortical carcinoma, metastasis, PET/CT, PSMA

(Clin Nucl Med 2018;00: 00-00)

Received for publication January 23, 2018; revision accepted February 16, 2018. From the *Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi; and ¡Department of Medicine, Postgraduate Institute of Medical Education and Research, Rohtak, India.

Conflicts of interest and sources of funding: none declared.

Author Contributions: S. Arora, N.A.D., and S. Aggarwal: manuscript preparation, literature search, patient management. A.P .: scan acquisition, reporting, and manuscript preparation. A.B. and G.A .: scan acquisition and manuscript preparation. C.B: manuscript review and patient management. M.T .: manuscript preparation and literature search.

Correspondence to: Nishikant Avinash Damle, MD, DNB, Department of Nuclear Medicine, All India Institute of Medical Sciences, Ansari Nagar (East), New Delhi 110029, India. E-mail: nkantdamle@gmail.com.

Copyright @ 2018 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 0363-9762/18/0000-0000

DOI: 10.1097/RLU.0000000000002064

REFERENCES

1. Kerkhofs T, Verhoeven RH, Van der Zwan JM, et al. Adrenocortical carci- noma: a population-based study on incidence and survival in the Netherlands since 1993. Eur J Cancer. 2013;49:2579-2586.

2. Schulick RD, Brennan MF. Long-term survival after complete resection and repeat resection in patients with adrenocortical carcinoma. Ann Surg Oncol. 1999;6:719-726.

3. Datrice NM, Langan RC, Ripley RT, et al. Operative management for recurrent and metastatic adrenocortical carcinoma. J Surg Oncol. 2012;105:709-713.

4. Allolio B, Fassnacht M. Clinical review: adrenocortical carcinoma: clinical update. J Clin Endocrinol Metab. 2006;91:2027-2037.

5. Bernini GP, Moretti A, Bonadio AG, et al. Angiogenesis in human normal and pathologic adrenal cortex. J Clin Endocrinol Metab. 2002;87: 4961-4965.

6. Chang SS, Reuter VE, Heston WD, et al. Five different anti-prostate-specific membrane antigen (PSMA) antibodies confirm PSMA expression in tumor- associated neovasculature. Cancer Res. 1999;59:3192-3198.

7. Morigi JJ, Stricker PD, van Leeuwen PJ, et al. Prospective comparison of 18F-fluoromethylcholine versus 68Ga-PSMA PET/CT in prostate cancer pa- tients who have rising PSA after curative treatment and are being considered for targeted therapy. J Nucl Med. 2015;56:1185-1190.

8. Shetty D, Loh H, Bui C, et al. Elevated 68 Ga prostate-specific membrane anti- gen activity in metastatic non-small cell lung cancer. Clin Nucl Med. 2016;41: 414 416.

9. Huang YT, Fong W, Thomas P. Rectal carcinoma on 68Ga-PSMA PET/CT. Clin Nucl Med. 2016;41:167-168.

10. Crowley MJ, Scognamiglio T, Liu YF, et al. Prostate-specific membrane antigen is a potential antiangiogenic target in adrenocortical carcinoma. J Clin Endocrinol Metab. 2016;101:981-987.

FIGURE 1. FDG PET/CT MIP (A), axial PET (B, C), CT (D, E), and fused PET/CT (F, G) sections showing large parenchymal soft tissue lesions in bilateral lungs with increased FDG uptake in a 27-year-old man with history of adrenocortical carcinoma (ACC). The patient had prior history of left adrenalectomy and was later started on mitotane therapy for metastatic lung lesions; however, this follow-up FDG PET/CT showed a slight increase in the size of the lung lesions. Adrenocortical carcinoma is a rare tumor with aggressive course and poor prognosis with annual incidence of 0.5 to 2.0 per million people.1 Complete surgical resection is the definite treatment, but still more than 50% of patients have local recurrences.2 Even for recurrent and metastatic lesions, metastectomy in the liver, lung, and nodes with debulking for those who have functional tumor has been tried, and it has been shown to increase disease-free survival.3 Mitotane has been used for metastatic ACC, although prediction of response is very difficult.4

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FIGURE 2. 68Ga prostate-specific membrane antigen (PSMA) PET/CT maximum intensity projection (A), axial PET (B, C), CT (D, E), and fused PET/CT (F, G) sections showing parenchymal soft tissue lesions in bilateral lungs with increased PSMA uptake with no abnormal uptake in postoperative left adrenal bed (evident from maximum intensity projection image, axial section not shown in figure). Because ACC is an orphan cancer with no definitive cure and poor prognosis, based on the previous preliminary reports describing PSMA expression in different malignant lesions, a PSMA PET/CT was planned. Angiogenesis and neovascularization are critical for tumor growth and vascular endothelial growth factor, which is a proangiogenic growth factor that has been shown to be up-regulated in ACC. It has been shown previously that the uptake of PSMA occurs in the endothelium of tumor neovasculature due to abnormal protein expression.6 Recent studies have also shown PSMA expression on 68Ga PSMA PET/CT in prostate cancer7 and other nonprostatic malignancies including lung cancer,8 pancreatic cancer, thyroid cancers, colon cancer,9 and so on. Crowley et al10 have also previously shown an elevated level of PSMA in ACC neovasculature compared with all benign tissue by quantitative polymerase chain reaction.

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