Proof of Concept: Evidence of Metastatic Pancreatic Ductal Adenocarcinoma Demonstrating PSMA Uptake on 68Ga-PSMA-11 PET/CT

INTRODUCTION

Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein abundantly expressed in prostate carcinoma and increasingly recognized in the neovasculature of various solid tumors.^[1-7] However, until now, no published evidence exists of PSMA uptake in metastatic lesions of pancreatic ductal adenocarcinoma. We present the case of a metastatic pancreatic ductal adenocarcinoma where metastatic sites demonstrated PSMA uptake, providing the first imaging proof-of-concept in this clinical context.

CASE REPORT

A 70-year-old male with pancreatic ductal adenocarcinoma underwent Whipple’s procedure and adjuvant chemotherapy (7 cycles of gemcitabine with capecitabine) in 2021 and recurred after 3 years, for which he received 6 cycles of NAB paclitaxel chemotherapy. As part of routine restaging, he underwent 18F-fluorodeoxyglucose positron emission tomography omputed tomography (18F-FDG PET CT), which demonstrated recurrence at the anastomotic site and metastatic liver lesions, left supraclavicular and paratracheal lymph nodes, and widespread bony lesions. Fine needle aspiration cytology from the left supraclavicular lymph node showed adenocarcinoma cells. Tumour markers were elevated with S.CA 19.9: 6672 U/ml(0-37U/ml) and S. Carcinoembryonic antigen: 143ng/ml(0-5ng/ml). As a part of an ongoing study following due ethics committee approval (AIIMSA00227/13.12.2023, RT-09/18.01.2024), written informed consent was taken from the patient to undergo 68Ga-PSMA-11 PET/CT to assess PSMA expression in the disease sites. The imaging findings on ⁶⁸GaPSMA-11 PET/CT and ¹⁸F-FDG PET/CT are shown in Fig 1.

Close

Fig 1:

(a) Maximum intensity projection (MIP) image from 68Ga-prostate-specific membrane antigen (PSMA)-11 positron emission tomography computed tomography (PET/CT) demonstrates moderate-to-intense, heterogeneous PSMA uptake in the disease sites- (b and c- Axial fused and CT images ; white arrow in b) gastrojejunostomy anastomotic site; (d-e - Axial fused and CT images) in the metastatic bony lesions in sacrum and ( f-g- Axial fused and CT images) in D3 of the thoracic vertebra. (h) MIP image from 18F-fluorodeoxyglucose PET/CT, which established the metastatic nature of the disease, shows widespread FDG-avid disease, and overall concordant distribution is noted between the two tracers

Export to PPT

These findings represent the first demonstration of PSMA uptake in metastatic pancreatic ductal adenocarcinoma lesions.

DISCUSSION

This case provides proof of concept that 68 Ga-PSMA-11 PET can detect metastatic pancreatic ductal adenocarcinoma. PSMA expression in tumour neovasculature is the likely mechanism explaining tracer uptake.^[8,9] Previous published literature states that histopathologically, there is lack of PSMA expression in the pancreatic ductal adenocarcinoma tumour cells, but there is PSMA expression in the tumour-associated neovasculature.^[8,10,11]

PSMA expression is noted intumor-associated neovasculature in many different nonprostatic solid malignancies, and a few also express PSMA on the tumour cells.^[2] Many studies have highlighted imaging evidence of in vivo PSMA uptake in a range of these nonprostatic malignancies, including thyroid, renal, salivary gland tumours, breast, and gliomas,^{[1,2,6,12-15]} and even in primary malignant pancreatic tumours.^[7] However, scan-based evidence in metastatic pancreatic ductal adenocarcinoma lesions is scarcely seen.

This case highlights two important issues. From an imaging standpoint, 68Ga-PSMA-11 PET contributes to staging and disease burden assessment in metastatic pancreatic ductal adenocarcinoma.

From a theranostic perspective, uptake in metastatic lesions raises the possibility of targeted radionuclide therapy with 177Lu-PSMA-617. This proof-of-concept opens the door to systematic studies evaluating the same.

CONCLUSION

Metastatic pancreatic ductal adenocarcinoma shows PSMA positivity on 68Ga-PSMA-11 PET/CT, which helps in disease burden assessment and opens up further exploration of PSMA as a thernostic target in the metastatic setting.