Differentiating benign and malignant pancreatic masses: Ga-68 PSMA PET/CT as a new diagnostic avenue

Background: Despite recent advances in the multimodal treatment of pancreatic ductal adenocarcinoma (PDAC), overall survival remains poor with a 5-year cumulative survival of approximately 10%. Neoadjuvant (chemo- and/or radio-) therapy is increasingly incorporated in treatment strategies for patients with (borderline) resectable and locally advanced disease. Neoadjuvant therapy aims to improve radical resection rates by reducing tumor mass and (partial) encasement of important vascular structures, as well as eradicating occult micrometastases. Results from recent multicenter clinical trials evaluating this approach demonstrate prolonged survival and increased complete surgical resection rates (R0). Currently, tumor response to neoadjuvant therapy is monitored using computed tomography (CT) following the RECIST 1.1 criteria. Accurate assessment of neoadjuvant treatment response and tumor resectability is considered a major challenge, as current conventional imaging modalities provide limited accuracy and specificity for discrimination between necrosis, fibrosis, and remaining vital tumor tissue. As a consequence, resections with tumor-positive margins and subsequent early locoregional tumor recurrences are observed in a substantial number of patients following surgical resection with curative intent. Of these patients, up to 80% are diagnosed with recurrent disease after a median disease-free interval of merely 8 months. These numbers underline the urgent need to improve imaging modalities for more accurate assessment of therapy response and subsequent re-staging of disease, thereby aiming to optimize individual patient’s treatment strategy. In cases of curative intent resection, additional intra-operative real-time guidance could aid surgeons during complex procedures and potentially reduce the rate of incomplete resections and early (locoregional) tumor recurrences. In recent years intraoperative imaging in cancer has made a shift towards tumor-specific molecular targeting. Several important molecular targets have been identified that show overexpression in PDAC, for example: CA19.9, CEA, EGFR, VEGFR/VEGF-A, uPA/uPAR, and various integrins. Tumor-targeted PET/CT combined with intraoperative fluorescence imaging, could provide valuable information for tumor detection and staging, therapy response evaluation with re-staging of disease and intraoperative guidance during surgical resection of PDAC. Methods: A literature search in the PubMed database and (inter)national trial registers was conducted, focusing on studies published over the last 15 years. Data and information of eligible articles regarding PET/CT as well as fluorescence imaging in PDAC were reviewed. Areas covered: This review covers the current strategies, obstacles, challenges, and developments in targeted tumor imaging, focusing on the feasibility and value of PET/CT and fluorescence imaging for integration in the work-up and treatment of PDAC. An overview is given of identified targets and their characteristics, as well as the available literature of conducted and ongoing clinical and preclinical trials evaluating PDAC-targeted nuclear and fluorescent tracers.

Section: Molecular Targets In Pancreatic Ductal Adenocarcinoma (Pdac)mentioning

confidence: 99%

Section: Positron Emission Tomography—computed Tomography (Pet/ct)mentioning

confidence: 99%

Section: Table A1mentioning

confidence: 99%

See 1 more Smart Citation

Overview and Future Perspectives on Tumor-Targeted Positron Emission Tomography and Fluorescence Imaging of Pancreatic Cancer in the Era of Neoadjuvant Therapy

Dam

Vuijk

Stibbe

et al. 2021

“…Radiolabelled PSMA-targeted PET-CT has proven highly successful for the primary staging and restaging of prostate cancer patients and is currently being implemented worldwide [ 55 , 56 ]. PSMA expression can be imaged by labelling small inhibitor molecules with PET radionuclides, i.e., 18 F or 68 Ga [ 57 ] ( Figure 1 and Table 1 ).…”

Section: Part 1: Tumour-targeted Tracers For the Detection Of Pancreatic Cancermentioning

confidence: 99%

Molecular Targeted Positron Emission Tomography Imaging and Radionuclide Therapy of Pancreatic Ductal Adenocarcinoma

Poels

Vuijk

Vahrmeijer

et al. 2021

Pancreatic ductal adenocarcinoma (PDAC) has an inauspicious prognosis, mainly due to difficulty in early detection of the disease by the current imaging modalities. The upcoming development of tumour-specific tracers provides an alternative solution for more accurate diagnostic imaging techniques for staging and therapy response monitoring. The future goal to strive for, in a patient with PDAC, should definitely be first to receive a diagnostic dose of an antibody labelled with a radionuclide and to subsequently receive a therapeutic dose of the same labelled antibody with curative intent. In the first part of this paper, we summarise the available evidence on tumour-targeted diagnostic tracers for molecular positron emission tomography (PET) imaging that have been tested in humans, together with their clinical indications. Tracers such as radiolabelled prostate-specific membrane antigen (PSMA)—in particular, 18F-labelled PSMA—already validated and successfully implemented in clinical practice for prostate cancer, also seem promising for PDAC. In the second part, we discuss the theranostic applications of these tumour-specific tracers. Although targeted radionuclide therapy is still in its infancy, lessons can already be learned from early publications focusing on dose fractioning and adding a radiosensitiser, such as gemcitabine.

“…In this context, PET/CT could provide useful information aimed at improving diagnosis considering its high sensitivity but not replacing other imaging techniques due to low specificity [25]. In a retrospective study by Ergul et al, PET/CT showed a sensitivity and specificity of 100% and 89.5% in the differential diag-nosis between malignant and benign lesions [26], while in a recent prospective study by Krishnaraju et al, sensitivity and specificity decreased to 89% and 57%, respectively [27]. It has been reported a possible increase of the diagnostic performance of PET/CT by using SUV cut-off and FDG uptake pattern to discriminate benign vs. malignant lesions [28,29].…”

Section: The Role Of 18 F-fdg Pet/ct In Pc Differential Diagnosismentioning

confidence: 99%

The Role of Positron Emission Tomography/Computed Tomography (PET/CT) for Staging and Disease Response Assessment in Localized and Locally Advanced Pancreatic Cancer

Ghidini

Vuozzo

Galassi

et al. 2021

Pancreatic Cancer (PC) has a poor prognosis, with a 5-year survival rate of only 9%. Even after radical surgical procedures, PC patients have poor survival rates, with a high chance of relapse (70–80%). Imaging is involved in all aspects of the clinical management of PC, including detection and characterization of primary tumors and their resectability, assessment of vascular, perineural and lymphatic invasion and detection of distant metastases. The role of Positron Emission Tomography/Computed Tomography (PET/CT) in detecting PC is still controversial, with the international guidelines not recommending its routine use. However, in resectable PC, PET/CT may play a role in assessing PC stage and grade and potential resectability after neoadjuvant treatment. Quantitative image analysis (radiomics) and new PET/CT radiotracers account for future developments in metabolic imaging and may further improve the relevance of this technique in several aspects of PC. In the present review, the current state of the art and future directions of PET/CT in resectable PC are presented.