Evaluation of advanced hepatocellular carcinoma with 68Ga-PSMA PET/CT, a prospective study!

Introduction: Early and accurate diagnosis of HCC is essential for better patient care and their treatment. Triple phase computed tomography (CT), and magnetic resonance (MR) imaging corroborated with serum alpha-fetoprotein value are routinely done for diagnosis. In doubtful case, histopathological examination can help to characterize the histological subtypes, grading and differential diagnosis of tumors and is considered the gold standard for precise diagnosis. Imaging of hepatocellular carcinoma (HCC) at diagnosis is challenging & assessment of recurrence following treatment is also even harder. Positron emission tomography (PET) using ¹⁸F-Fluorodeoxyglucose (¹⁸F-FDG) has a limited role in evaluating patients with HCC. Since PSMA expression in advanced hepatocellular carcinoma is a known phenomenon. PSMA receptors are located in the endothelium and have shown their correlation with VEGF expression in highly vascular tumors. There are a few studies and case reports that have documented radiotracer uptake at the involved segment of liver in patients with primary hepatocellular carcinoma. Therefore, we planned the present study to evaluate the role of ⁶⁸Ga-PSMA in HCC patients and compare with conventional imaging (CECT/MRI).

Methods: Radiologically and/or histopathologically confirmed patients of HCC were prospectively included in this study. PSMA. The cases having doubtful diagnosis on conventional imaging & histopathology were excluded from the study. Imaging was performed after 30-45mins of intravenous injection of 3-5mCi of Ga-68 PSMA on dedicated PET/CT scanners. All the patients had undergone CECT and/or MRI scan and estimation of serum alpha-fetoprotein, as part of routine workup prior to PSMA PET/CT. Acquired whole-body PET/CTs were analysed both visually and quantitatively by two experienced nuclear medicine physicians.

Results: Forty-one (41) patients (36 male, 5 female) with mean age 53.9 ± 10.9 years of known HCC underwent ⁶⁸Ga-PSMA PET/CT. In 41 patients, there were 108 lesions on conventional imaging, out of 108 lesions 84 lesions were positive in PSMA scan. Of 41 patients, 18 patients had single lesion on CECT/MRI and 23 patients had multifocal (>2) lesions in liver. On ⁶⁸Ga-PSMA scan, 38 of 41 patients were positive on (in atleast one liver lesion). Of the 18 patients with single lesion on CT/MRI, 16 showed concordant single lesion on PSMA while 2 patients showed additional liver lesions (one patients showed 2 additional lesions and other showed >2 additional lesions) on PSMA scan.

Of the 23 patients with multiple hepatic lesions on CT/MRI, no PSMA uptake was observed in 3 patients; 7 patients showed PSMA uptake only in single liver lesion and 13 patients had PSMA uptake in multiple lesions. Spearman correlation coefficient applied on tumor marker (Serum alpha-feto-protein) and tumor SUVmax in PSMA PET/CT was 0.070 and p value to know the study significance was 0.692. Thus, there was no correlation observed between S.AFP level and SUVmax. of tumor on ⁶⁸Ga-PSMA PET/CT.

Assuming conventional imaging as gold standard, sensitivity of 92.6% and positive predictive value of 100% was observed in PSMA scan.

Conclusions: ⁶⁸Ga- PSMA PET/CT may be useful as complimentary modality to conventional imaging for lesion characterization, the staging and/or restaging and response evaluation after therapy for advanced HCC with an added advantage of being used as a theranostic modality in patients with limited therapeutic options particularly when expressing PSMA with high tumor to background ratio (>1). Alternatively, ⁶⁸Ga-PSMA PET with contrast enhanced CT may be used alone as a substitute of CECT/MRI for detection of advanced hepatocellular carcinoma in certain circumstances.