2. Academic Validation
  3. Fibroblast activation protein targeted therapy using [177Lu]FAPI-46 compared with [225Ac]FAPI-46 in a pancreatic cancer model

Fibroblast activation protein targeted therapy using [177Lu]FAPI-46 compared with [225Ac]FAPI-46 in a pancreatic cancer model

  • Eur J Nucl Med Mol Imaging. 2022 Feb;49(3):871-880. doi: 10.1007/s00259-021-05554-2.
Yuwei Liu 1,  Tadashi Watabe 2 3,  Kazuko Kaneda-Nakashima 4 5,  Yoshifumi Shirakami 4,  Sadahiro Naka 6,  Kazuhiro Ooe 1 4,  Atsushi Toyoshima 4,  Kojiro Nagata 7,  Uwe Haberkorn 8 9 10,  Clemens Kratochwil 8,  Atsushi Shinohara 4 11,  Jun Hatazawa 4 12,  Frederik Giesel 4 8 13
Affiliations

Affiliations

  • 1 Department of Nuclear Medicine and Tracer Kinetics, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
  • 2 Department of Nuclear Medicine and Tracer Kinetics, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan. watabe@tracer.med.osaka-u.ac.jp.
  • 3 Institute for Radiation Sciences, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan. watabe@tracer.med.osaka-u.ac.jp.
  • 4 Institute for Radiation Sciences, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
  • 5 Core for Medicine and Science Collaborative Research and Education, Project Research Center for Fundamental Sciences, Graduate School of Science, Osaka University, Suita, Osaka, Japan.
  • 6 Department of Radiology, Osaka University Hospital, Suita, Osaka, Japan.
  • 7 Radioisotope Research Center, Institute for Radiation Sciences, Osaka University, Suita, Osaka, Japan.
  • 8 Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany.
  • 9 Clinical Cooperation Unit Nuclear Medicine DKFZ, Heidelberg, Germany.
  • 10 Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL), Heidelberg, Germany.
  • 11 Department of Chemistry, Graduate School of Science, Osaka University, Toyonaka, Osaka, Japan.
  • 12 Research Center for Nuclear Physics, Osaka University, Suita, Osaka, Japan.
  • 13 Department of Nuclear Medicine, University Hospital Düsseldorf, Düsseldorf, Germany.
PMID: 34537893 DOI: 10.1007/s00259-021-05554-2
Abstract

Purpose: Fibroblast activation protein (FAP), which has high expression in cancer-associated fibroblasts of epithelial cancers, can be used as a theranostic target. Our previous study used 64Cu and 225Ac-labelled FAP inhibitors (FAPI-04) for a FAP-expressing pancreatic Cancer xenograft imaging and therapy. However, the optimal therapeutic radionuclide for FAPI needs to be investigated further. In this study, we evaluated the therapeutic effects of beta-emitter (177Lu)-labelled FAPI-46 and alpha-emitter (225Ac)-labelled FAPI-46 in pancreatic Cancer models.

Methods: PET scans (1 h post injection) were acquired in PANC-1 xenograft mice (n = 9) after the administration of [18F]FAPI-74 (12.4 ± 1.7 MBq) for the companion imaging. The biodistribution of [177Lu]FAPI-46 and [225Ac]FAPI-46 were evaluated in the xenograft model (total n = 12). For the determination of treatment effects, [177Lu]FAPI-46 and [225Ac]FAPI-46 were injected into PANC-1 xenograft mice at different doses: 3 MBq (n = 6), 10 MBq (n = 6), 30 MBq (n = 6), control (n = 4) for [177Lu]FAPI-46, and 3 kBq (n = 3), 10 kBq (n = 2), 30 kBq (n = 6), control (n = 7) for [225Ac]FAPI-46. Tumour sizes and body weights were followed.

Results: [18F]FAPI-74 showed rapid clearance by the kidneys and high accumulation in the tumour and intestine 1 h after administration. [177Lu]FAPI-46 and [225Ac]FAPI-46 also showed rapid clearance by the kidneys and relatively high accumulation in the tumour at 3 h. Both [177Lu]FAPI-46 and [225Ac]FAPI-46 showed tumour-suppressive effects, with a mild decrease in body weight. The treatment effects of [177Lu]FAPI-46 were relatively slow but lasted longer than those of [225Ac]FAPI-46.

Conclusion: This study suggested the possible application of FAPI radioligand therapy in FAP-expressing pancreatic Cancer. Further evaluation is necessary to find the best radionuclide with shorter half-life, as well as the combination with therapies targeting tumour cells directly.

Keywords

Actinium; FAPI; Fibroblast activation protein; Lutetium; Pancreatic cancer.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-147173
    99.84%, PET Tracer
    FAP