A novel molecular imaging probe [99mTc]Tc-HYNIC-FAPI targeting cancer-associated fibroblasts

Abstract

Fibroblast activation protein (FAP) is higher expressed on cancer-associated fibroblasts (CAFs) in most malignant epithelial neoplasms, which is lower expressed in normal tissues. As a promising small molecular probe, FAP inhibitor (FAPI) shows the specific binding to FAP. This study aimed to explore a novel molecular probe [99mTc]Tc-HYNIC-FAPI targeting CAFs. The in vitro characteristics of the probe were also evaluated. The FAPI targeting FAP was designed, synthesized and conjugated with the chelator 6-hydrazinylnicotinic acid (HYNIC) for radiolabeling with 99mTc. The radiolabeling yield, radiochemical purity and stability were evaluated by Instant thin-layer chromatography (ITLC) and High performance liquid chromatography (HPLC). Lipophilicity was performed by the distribution coefficient test. The binding and migration ability of the probe was assessed using the FAP transfected tumor cell line. The radiolabeling yield of [99mTc]Tc-HYNIC-FAPI was (97.29 ± 0.46) %. The radiochemical purity was more than 90% and kept stable until 6 h. The radioligand was shown as lower lipophilicity, of which logD7.4 value was − 2.38 $$\pm$$ ± 0.13. In vitro experiments, the results indicated that the probe showed binding properties, and inhibited the migration of tumor cells. The novel [99mTc]Tc-HYNIC-FAPI probe was successfully radiosynthesized and exhibited good radiochemical purity, stability and in vitro binding ability to tumor cells. The [99mTc]Tc-HYNIC-FAPI will be a promising SPECT/CT imaging probe.

99mTc-HYNIC-FAPI-46 SPECT/CT Uptake in Lactating Breasts

“…The decision was made at least partly due to her family history of multiple endocrine neoplasia type 2A in her brother, which could be finally detected using the FAPI scan along with lower costs as compared with 68 Ga-FAPI PET/CT scan. [1][2][3][4] One hour after IV injection of 740 MBq of 99m Tc-HYNIC-FAPI-46, whole-body planar scintigraphy was performed using a dual-head gamma camera parallel-hole collimator (12 cm/min table speed, 140 keV energy window with 10% width). On the whole-body image, 2 areas of abnormal increased activity were noted in both lower thoracic regions more prominent on the right side (A), which were located in both breasts more noticeable on the right side on SPECT/CT images (B-G).…”

“…Because her cervical ultrasound and abdominal MRI showed inconclusive findings in the neck and liver, the team decided to perform 99m Tc-HYNIC-FAPI-46 imaging. The decision was made at least partly due to her family history of multiple endocrine neoplasia type 2A in her brother, which could be finally detected using the FAPI scan along with lower costs as compared with 68 Ga-FAPI PET/CT scan 1–4 . One hour after IV injection of 740 MBq of 99m Tc-HYNIC-FAPI-46, whole-body planar scintigraphy was performed using a dual-head gamma camera parallel-hole collimator (12 cm/min table speed, 140 keV energy window with 10% width).…”