Impact of FAPI-PET/CT on Target Volume Definition in Radiation Therapy of Locally Recurrent Pancreatic Cancer

Liermann, Jakob; Syed, Mustafa; Ben‐Josef, Edgar; Schubert, Kai; Schlampp, Ingmar; Sprengel, Simon David; Ristau, Jonas; Weykamp, Fabian; Röhrich, Manuel; Koerber, Stefan A.; Haberkorn, Uwe; Debus, Jürgen; Herfarth, Klaus; Giesel, Frederik L.; Naumann, Patrick

doi:10.3390/cancers13040796

Cited by 34 publications

(22 citation statements)

References 32 publications

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“…FAPI-PET/CT may be a better method of facilitating the radiotherapeutic management of PDACs based on its more accurate depiction of the tumor extent. FAPI-PET/CT also showed an improved target volume definition and consistency compared with contrast-enhanced CT [ 105 ].…”

Section: Malignant Conditionsmentioning

confidence: 99%

FAP and FAPI-PET/CT in Malignant and Non-Malignant Diseases: A Perfect Symbiosis?

Dendl

Koerber

Kratochwil

et al. 2021

Cancers

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A fibroblast activation protein (FAP) is an atypical type II transmembrane serine protease with both endopeptidase and post-proline dipeptidyl peptidase activity. FAP is overexpressed in cancer-associated fibroblasts (CAFs), which are found in most epithelial tumors. CAFs have been implicated in promoting tumor cell invasion, angiogenesis and growth and their presence correlates with a poor prognosis. However, FAP can generally be found during the remodeling of the extracellular matrix and therefore can be detected in wound healing and benign diseases. For instance, chronic inflammation, arthritis, fibrosis and ischemic heart tissue after a myocardial infarction are FAP-positive diseases. Therefore, quinoline-based FAP inhibitors (FAPIs) bind with a high affinity not only to tumors but also to a variety of benign pathologic processes. When these inhibitors are radiolabeled with positron emitting radioisotopes, they provide new diagnostic and prognostic tools as well as insights into the role of the microenvironment in a disease. In this respect, they deliver additional information beyond what is afforded by conventional FDG PET scans that typically report on glucose uptake. Thus, FAP ligands are considered to be highly promising novel tracers that offer a new diagnostic and theranostic potential in a variety of diseases.

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Section: Malignant Conditionsmentioning

confidence: 99%

FAP and FAPI-PET/CT in Malignant and Non-Malignant Diseases: A Perfect Symbiosis?

Dendl

Koerber

Kratochwil

et al. 2021

Cancers

Self Cite

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“…Geist et al (51) Hepatic lesions 8 Dynamic 68 Ga-FAPI PET scan allows differentiation between hepatocellular carcinoma and non-HCC lesions Röhrich et al (52) Pancreatic ductal adenocarcinomas 19 68 Ga-FAPI PET/CT allowed restaging in half of the patients with PDAC and the majority of patients with recurrent disease compared with standard-of-care imaging. Liermann et al (53) Pancreatic cancer 7 FAPI PET/CT seems to be a superior imaging modality to contrast-enhanced CT, which is the current gold standard in pancreatic cancer with the potential as a tool for automatic target volume definition before radiotherapy. Kömek et al (54) Breast cancer 20 68 Ga-FAPI04 PET/CT is superior to 18F-FDG PET/CT in detecting primary tumors and metastases in breast cancer patients.…”

Section: Syed Et Al (36)mentioning

confidence: 99%

“…In another study, Liermann et al. ( 53 ) compared 68 Ga-FAPI04 PET/CT with ceCT in seven recurrent pancreatic patients for radiotherapy planning. However, both studies did not use 18 F-FDG PET/CT for comparison.…”

Section: Fibroblast Activation Protein-targeted Imaging In Oncologymentioning

confidence: 99%

Fibroblast-Activated Protein Inhibitor PET/CT: Cancer Diagnosis and Management

2021

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Fibroblast activation protein (FAP), overexpressed on cancer-associated fibroblasts (CAFs), is a novel target for molecular imaging of various tumors. Recently, the development of several small-molecule FAP inhibitors for radiolabeling with 68Ga has resulted in the emergence of studies evaluating its clinical role in cancer imaging. Preliminary findings have demonstrated that, in contrast to radiotracers taking advantage of cancer-specific targets such as PSMA and DOTATATE, FAPs as a target are the most promising that can compete with 18FDG in terms of widespread indications. They also have the potential to overcome the shortcomings of 18FDG, particularly false-positive uptake due to inflammatory or infectious processes, low sensitivity in certain cancer types, and radiotherapy planning. In addition, the attractive theranostic properties may facilitate the treatment of many refractory cancers. This review summarizes the current FAP variants and related clinical studies, focusing on radiopharmacy, dosimetry, and diagnostic and theranostic applications.

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“…In conclusion, the use of 68 Ga-FAPI PET/CT showed promising results to improve diagnosis and (re)staging of PDAC, and might in the future be combined with FAP-targeted therapies (e.g., radionuclide therapy), which has already been evaluated in the preclinical setting by Lui et al, demonstrating a significant tumor suppressing effect using 177 Lu-FAPI-46 and 225 Ac-FAPI-46 in PANC-1 xenograft mouse models. [ 167 , 168 , 169 ].…”

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

confidence: 99%

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

Cancers

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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.

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Impact of FAPI-PET/CT on Target Volume Definition in Radiation Therapy of Locally Recurrent Pancreatic Cancer

Cited by 34 publications

References 32 publications

FAP and FAPI-PET/CT in Malignant and Non-Malignant Diseases: A Perfect Symbiosis?

FAP and FAPI-PET/CT in Malignant and Non-Malignant Diseases: A Perfect Symbiosis?

Fibroblast-Activated Protein Inhibitor PET/CT: Cancer Diagnosis and Management

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

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