Abstract
1047
Background: Fibroblast activation protein (FAP) is overexpressed in cancer associated fibroblasts, which is known to promote tumor growth and progression. Since it is expressed in many human epithelial cancers but not in normal organs, FAP can be used as an excellent target for the theranostics in oncology. Based on a FAP inhibitor (FAPI), our collaborator recently demonstrated [68Ga]FAPI-04 PET can be used for a cancer specific diagnosis in patients with various cancers. This time, we used [64Cu]FAPI-04 to evaluate the biodistribution in mice with human pancreatic cancer xenografts.
Methods: Male nude mice (body weight = 22.5 ± 1.2 g) were prepared by subcutaneous injection with human pancreatic cancer cells (PANC-1 or MIAPaCa2, n=4 for each, respectively). Tumor xenograft mice were investigated using a small animal PET scanner (Siemens Inveon PET/CT) three weeks after the implantation under isoflurane anesthesia. After intravenous injection of [64Cu]FAPI-04 (7.21 ± 0.46 MBq), dynamic scan was acquired in one mouse of PANC-1 group and delayed PET scans were acquired 2hrs after injection in all mice. Regions of interest were placed on the tumor, muscle, heart, liver, intestine, kidneys and bladder using PMOD (Ver 3.6). Immunohistochemical staining was performed for the tumor xenograft using FAP-alpha antibody (Abcam).
Results: Dynamic imaging showed a fast clearance through kidneys and a slow washout of the tumors. In the delayed PET imaging, both of PANC-1 and MIAPaCa2 xenograft models showed mild uptake in the tumors and relatively high uptake in the liver and intestine. The SUVmean of delayed scan were 0.23 ± 0.07 in the PANC-1 xenograft, 0.17 ± 0.03 in the MIAPaCa2 xenograft, 0.04 ± 0.03 in the muscle, 0.10 ± 0.03 in the heart, 0.91 ± 0.23 in the liver, 0.32 ± 0.17 in the intestine, 0.52 ± 0.48 in the kidneys, and 26.72±31.11 in the bladder, respectively. Immunohistochemical staining using FAP-alpha antibody revealed the abundant FAP expression in both PANC-1 and MIAPaCa2 xenografts.
Conclusions: This study showed the feasibility of [64Cu]FAPI-04 for the diagnosis of FAP-expressing pancreatic cancer. Since the half-life of 64Cu (12.7 hrs) is longer than 68Ga (68mins), it’s possible to trace the biodistribution of FAPI-04 for a longer time, which enables precise pre-treatment evaluation for the targeted radionuclide therapy using Lu-177 (6.7 days) or 225Ac (10 days).Fig.1 Delayed PET imaging of PANC-1 and MIAPaCa2 xenograft models.Fig.2 The uptake in the tumor and normal organs at the delayed PET scan.Fig.3 Immunohistochemical staining of the PANC-1 tumor xenograft using FAP-alpha antibody (left: low magnification, right: high magnification).