Ga-68-PSMA-11 PET/CT improves tumor detection and impacts management in patients with hepatocellular carcinoma (HCC)

Hirmas, Nader; Leyh, C; Sraieb, Miriam; Barbato, Francesco; Schaarschmidt, BM; Umutlu, L; Nader, Michael; Wedemeyer, H; Ferdinandus, Justin; Rischpler, Christoph; Herrmann, Ken; Costa, P.; Lange, CM; Weber, MM; Fendler, WP

doi:10.1055/s-0041-1726762

Cited by 5 publications

(9 citation statements)

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“…(8)(9)(10) Recent immunohistochemistry (IHC) reports suggest that there is higher-than-average expression of PSMA in HCC. (11) Anecdotal reports and retrospective studies (12)(13)(14) suggest that expression of PSMA in HCC can be detected noninvasively on 68 Ga-PSMA-11 PET. These data provide the rationale to prospectively investigate PSMA-targeted PET imaging as a foundational step toward the prospect of PSMA-targeted peptide receptor radionuclide therapy (PRRT) (e.g., 177 Lu-PSMA-617) in HCC.…”

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confidence: 99%

PSMA as a Theranostic Target in Hepatocellular Carcinoma: Immunohistochemistry and 68Ga‐PSMA‐11 PET Using Cyclotron‐Produced 68Ga

et al. 2021

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Prostate‐specific membrane antigen (PSMA) is a validated target for molecular diagnostics and targeted radionuclide therapy. Our purpose was to evaluate PSMA expression in hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and hepatic adenoma (HCA); investigate the genetic pathways in HCC associated with PSMA expression; and evaluate HCC detection rate with 68 Ga‐PSMA‐11 positron emission tomography (PET). In phase 1, PSMA immunohistochemistry (IHC) on HCC (n = 148), CCA (n = 111), and HCA (n = 78) was scored. In a subset (n = 30), messenger RNA (mRNA) data from the Cancer Genome Atlas HCC RNA sequencing were correlated with PSMA expression. In phase 2, 68 Ga‐PSMA‐11 PET was prospectively performed in patients with treatment‐naïve HCC on a digital PET scanner using cyclotron‐produced 68 Ga. Uptake was graded qualitatively and semi‐quantitatively using standard metrics. On IHC, PSMA expression was significantly higher in HCC compared with CCA and HCA ( P < 0.0001); 91% of HCCs (n = 134) expressed PSMA, which principally localized to tumor‐associated neovasculature. Higher tumor grade was associated with PSMA expression ( P = 0.012) but there was no association with tumor size ( P = 0.14), fibrosis ( P = 0.35), cirrhosis ( P = 0.74), hepatitis B virus ( P = 0.31), or hepatitis C virus ( P = 0.15). Overall survival tended to be longer in patients without versus with PSMA expression (median overall survival: 4.2 vs. 1.9 years; P = 0.273). FGF14 (fibroblast growth factor 14) mRNA expression correlated positively (rho = 0.70; P = 1.70 × 10 ‐5 ) and MAD1L1 (Mitotic spindle assembly checkpoint protein MAD1) correlated negatively with PSMA expression (rho = −0.753; P = 1.58 × 10 ‐6 ). Of the 190 patients who met the eligibility criteria, 31 patients with 39 HCC lesions completed PET; 64% (n = 25) lesions had pronounced 68 Ga‐PSMA‐11 standardized uptake value: SUV max (median [range] 9.2 [4.9‐28.4]), SUV mean 4.7 (2.4‐12.7), and tumor‐to‐liver background ratio 2 (1.1‐11). Conclusion: Ex vivo expression of PSMA in neovasculature of HCC translates to marked tumor avidity on 68 Ga‐PSMA‐11 PET, which suggests that PSMA has the potential as a theranostic target in patients with HCC.

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confidence: 99%

PSMA as a Theranostic Target in Hepatocellular Carcinoma: Immunohistochemistry and 68Ga‐PSMA‐11 PET Using Cyclotron‐Produced 68Ga

et al. 2021

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“…What distinguishes PSMA from other diagnostic markers of hepatic lesions is its potential theranostic applications. Recent studies have shown that PSMA-labeled radioligands can efficiently detect HCC and its metastasis and may affect HCC management 20–24. In some instances, PSMA-targeted PET in HCC was found to even be superior to conventional imaging techniques 21,23.…”

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confidence: 99%

“…Furthermore, lutetium-177-labeled PSMA shows promising results for successful endoradiotherapeutic treatment of metastatic hormone-sensitive and castration-resistant prostate cancer with survival benefits 12,13. Interestingly, PSMA PET avidity has also been reported to occur in nonprostatic malignancies to include glioblastoma,16 hematolymphoid malignancies,17,18 thyroid cancer,19 and HCC 20–24. For liver cancer, PSMA-targeted radioligands may have significant clinical implications as diagnostic imaging and management of HCC in cirrhotic patients remain challenging.…”

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confidence: 99%

“…12,13 Interestingly, PSMA PET avidity has also been reported to occur in nonprostatic malignancies to include glioblastoma, 16 hematolymphoid malignancies, 17,18 thyroid cancer, 19 and HCC. [20][21][22][23][24] For liver cancer, PSMA-targeted radioligands may have significant clinical implications as diagnostic imaging and management of HCC in cirrhotic patients remain challenging.…”

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PSMA Immunohistochemistry in Hepatic Neoplasms

Kmeid

Park²,

Chung

et al. 2022

American Journal of Surgical Pathology

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Accurate classification of well-differentiated hepatocellular neoplasms can be challenging especially in core biopsies. Prostatespecific membrane antigen (PSMA) has been shown to highlight tumor-associated neovasculature in many nonprostatic solid tumors including hepatocellular carcinoma (HCC). Archived 164 hepatectomies and explants with 68 HCCs, 31 hepatocellular adenoma (HA), 24 dysplastic nodules (DN), and 42 metastases were retrieved, and pathologic parameters were evaluated. Sensitivity, specificity, accuracy, positive, and negative predictive values for correct diagnosis of HCC were calculated for PSMA and CD34 immunostains in tissue sections and HCC tissue microarrays. PSMA positivity was defined as capillarized sinusoidal/tumor-associated vessel staining involving ≥ 5% of the tumor area. In all, 55/68 (80.9%) HCC and 37/ 42 (88.1%) of liver metastasis were PSMA positive. PSMA was negative in HA, DN, and background liver (100% specificity). CD34 had a 98.5% sensitivity but a 65.5% specificity in identifying HCC. PSMA sensitivity remained high in the HCC tissue microarray (89.7%). PSMA was more accurate than CD34 (95.5% vs. 69.7%) in distinguishing grade 1 HCC from HA and high-grade DN while retaining high sensitivity (80%). The degree of PSMA positivity in HCC was greater in older, male, and human immunodeficiency virus patients (P < 0.05). No associations were found between PSMA staining and other tumor parameters (P > 0.05). PSMA is a marker of neoangiogenesis with increased expression in both primary and metastatic hepatic malignancies. Neovascular PSMA expression is more specific and accurate than CD34 for differentiating HCC from benign and precursor hepatic lesions. Diagnostic and therapeutic utility of PSMA radioligands in malignant liver neoplasms warrant further clinical investigations.

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“…In HCC, 18 F-Fluoroethylcholine (surrogate for cell membrane biosynthesis) can be used [23,24]. Recently, the value of prostate specific membrane antigen (PSMA) ligand PET was evaluated in 40 HCC patients and demonstrated a high impact on the intended management approach [25].…”

Section: Patient Selection and Treatment Planning For Radioembolizationmentioning

confidence: 99%

Radioembolization, Principles and indications

Ahmadzadehfar

Ilhan²,

Lam

et al. 2022

Nuklearmedizin

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Ga-68-PSMA-11 PET/CT improves tumor detection and impacts management in patients with hepatocellular carcinoma (HCC)

Cited by 5 publications

References 0 publications

PSMA as a Theranostic Target in Hepatocellular Carcinoma: Immunohistochemistry and 68Ga‐PSMA‐11 PET Using Cyclotron‐Produced 68Ga

PSMA as a Theranostic Target in Hepatocellular Carcinoma: Immunohistochemistry and 68Ga‐PSMA‐11 PET Using Cyclotron‐Produced 68Ga

PSMA Immunohistochemistry in Hepatic Neoplasms

Radioembolization, Principles and indications

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