The role of [99mTc]Tc-HFAPi SPECT/CT in patients with malignancies of digestive system: first clinical experience

Abstract

Background Recently, PET/CT imaging with radiolabelled FAP inhibitors (FAPIs) has been widely evaluated in diverse diseases. However, rare report has been published using SPECT/CT, a more available imaging method, with [99mTc]Tc-labelled FAPI. In this study, we evaluated the potential effect of [99mTc]Tc-HFAPi in clinical analysis for digestive system tumours. Methods This is a single-centre prospective diagnostic efficiency study (Ethic approved No.: XJTU1AF2021LSK-021 of the First Affiliated Hospital of Xi’an Jiaotong University and ChiCTR2100048093 of the Chinese Clinical Trial Register). Forty patients with suspected or confirmed digestive system tumours underwent [99mTc]Tc-HFAPi SPECT/CT between January and June 2021. For dynamic biodistribution and dosimetry estimation, whole-body planar scintigraphy was performed at 10, 30, 90, 150, and 240 min post-injection in four representative patients. Optimal acquisition time was considered in all the patients at 60–90 min post-injection, then quantified or semi-quantified using SUVmax and T/B ratio was done. The diagnostic performance of [99mTc]Tc-HFAPi was calculated and compared with those of contrast-enhanced CT (ceCT) using McNemar test, and the changes of tumour stage and oncologic management were recorded. Results Physiological distribution of [99mTc]Tc-HFAPi was observed in the liver, pancreas, gallbladder, and to a lesser extent in the kidneys, spleen and thyroid. Totally, 40 patients with 115 lesions were analysed. The diagnostic sensitivity of [99mTc]Tc-HFAPi for non-operative primary lesions was similar to that of ceCT (94.29% [33/35] vs 100% [35/35], respectively; P = 0.5); in local relapse detection, [99mTc]Tc-HFAPi was successfully detected in 100% (n = 3) of patients. In the diagnosis of suspected metastatic lesions, [99mTc]Tc-HFAPi exhibited higher sensitivity (89.66% [26/29] vs 68.97% [20/29], respectively, P = 0.03) and specificity (97.9% [47/48] vs 85.4% [41/48], respectively, P = 0.03) than ceCT, especially with 100% (24/24) specificity in the diagnosis of liver metastases, resulting in 20.0% (8/40) changes in TNM stage and 15.0% (6/40) changes in oncologic management. Conclusion [99mTc]Tc-HFAPi demonstrates a greater diagnostic efficiency than ceCT in the detection of distant metastasis, especially in identifying liver metastases.

Synthesis and Preliminary Study of 99mTc-Labeled HYNIC-FAPi for Imaging of Fibroblast Activation Proteins in Tumors

“…These have only been applied in ovarian, pancreatic, and digestive cancers. 16,27 In this study, the hydrazine nicotinamide structure (HYNIC) was used as a chelator for 99m Tc, and after coupling with the FAP targeting molecule FAPI-04, HYNIC-FAPI-04 (HFAPi) was obtained.…”

“…The superior value of 68 Ga-FAPI PET/CT over 18 F-FDG in detecting primary and metastatic lesions in breast cancers has been reported. , Most radiotracers are limited to PET imaging, and few have been studied for SPECT imaging. These have only been applied in ovarian, pancreatic, and digestive cancers. , In this study, the hydrazine nicotinamide structure (HYNIC) was used as a chelator for 99m Tc, and after coupling with the FAP targeting molecule FAPI-04, HYNIC-FAPI-04 (HFAPi) was obtained.…”

99mTc-HFAPi imaging identifies early myocardial fibrosis in the hypertensive heart

“…In addition, 18 F-labeled or 68 Ga-labeled FAPI has a shorter half-life. 99m Tc-HFAPi has good target organ uptake, rapid renal clearance, and lower uptake in normal organs, resulting in a higher target-to-background ratio and better imaging time window [15]. However, 99m Tc-HFAPi also has some shortcomings, such as the low resolution of SPECT image acquisition, and the lack of standardization of imaging time points and myocardial image analysis methods.…”

“…In clinical application, radiochemical purity was more than 95%. The reaction mixture was filtered through a 0.20 mm Millex-LG filter (EMD Millipore, Burlington, Massachusetts, USA) before the injection of reagents [15].…”

“…Moreover, all the FAPI studies to date applied 18 F-labeled or 68 Ga-labeled FAPI, limiting its extensive application in clinical settings. To reduce the cost and facilitate a widespread application of FAPI imaging, we labeled and synthesized 99m Tc-HFAPi [15], which is easy to prepare and can be imaged using single-photon emission computed tomography (SPECT).…”