Prostate-specific Membrane Antigen Imaging in Recurrent Medullary Thyroid Cancer: A New Theranostic Tracer in the Offing?

Prostate-specific membrane antigen (PSMA) expression has been shown in neovasculature of various malignancies. Recurrent medullary thyroid cancer (MTC) is difficult to treat. We present the findings on PSMA-positron emission tomography/computed tomography (PET/CT) of a 68-year-old man with MTC, who presented with a recurrent left paratracheal mass and rising calcitonin. The scan revealed significant uptake on PSMA imaging but not on 68Ga-DOTANOC PET/CT. 177Lu-PRRT is one of the therapeutic options in patients with recurrent MTC, but in this case was not possible due to lack of somatostatin receptor expression. Imaging evidence of PSMA expression alerts us to the potential use of 177Lu-DKFZ-PSMA-617 therapy in such patients.

68Ga prostate-specific membrane antigen (PSMA)-positron emission tomography/computed tomography (PET/CT) is commonly used in the management of patients with prostate cancer. This scan has a theranostic role in a selected group of patients as of date. However, PSMA expression has also been reported previously in other malignancies such as breast, bladder, gastric, colon, renal cell carcinoma, rectum, lung, hepatocellular carcinoma, multiple myeloma, and follicular lymphoma and in some nonneoplastic conditions.[12345678] Few studies have shown expression of PSMA in thyroid cancer.[910111213] 177Lu/ 90Y DOTATATE therapy has been used previously in metastatic medullary thyroid cancer (MTC).[1415] Few earlier studies have reported PSMA expression in the endothelium of tumor neovasculature where there is abnormal protein expression and increased transcription of PSMA through activation of the transcriptional enhancer region in endothelial cells.[16] This 68-year-old man with MTC, who earlier underwent total thyroidectomy and left neck dissection as primary surgery and left modified radical neck dissection and radiotherapy for nodal recurrence, had persistently rising calcitonin (doubling time of ~9 months, raised from 36 to 107 ng/mL) and carcinoembryonic antigen level (27 ng/mL). He had recurrence for the second time, and options of surgery and radiotherapy were already exhausted. Option of using vandetanib/cabozantinib was unavailable. The patient also had a negative metaiodobenzylguanidine (MIBG) scan and somatostatin receptor PET/CT [Figure 1b and e], which ruled out 131I MIBG and 177Lu DOTATATE therapy. To explore the possibility of using 177Lu-DKFZ-PSMA 617 therapy, he underwent a 68Ga-PSMA PET/CT, which showed soft-tissue density lesion in the left paratracheal region, extending into tracheoesophageal groove with increased PSMA uptake [Figure 1c and f] “SUVmax-19.7, SUVmax liver-8.0”. The same mass was fluorodeoxyglucose positive [Figure 1a] but showed no significant uptake on 68Ga DOTANOC uptake [Figure 1b and e]. Further studies will help ascertain the utility of 177Lu-PSMA-DKFZ-617 in such patients with exhausted treatment options.

Figure 1

Maximum intensity projection images of 18F-fluorodeoxyglucose (a), 68Ga-DOTANOC (b), 68Ga-prostate-specific membrane antigen positron emission tomography/computed tomography (c), revealing increased uptake of 18F-fluorodeoxyglucose and 68Ga prostate-specific membrane antigen in the left paratracheal recurrent soft-tissue lesion, but no significant uptake on scan and somatostatin receptor positron emission tomography/computed tomography (thin black arrow). Axial computed tomography (d), fused 68Ga-DOTANOC (e), and 68Ga-prostate-specific membrane antigen positron emission tomography/computed tomography (f) images reveal soft-tissue density lesion in the left paratracheal region, extending into tracheoesophageal groove (d) with increased prostate-specific membrane antigen uptake (black arrow, “SUVmax-19.7, SUVmax liver-8.0”)

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