Longitudinal MicroSPECT Imaging of Systemic Sclerosis Model Mice with [^99mTc]Tc-HYNFA via Folate Receptor Targeting

Noninvasive single-photon emission computed tomography (SPECT) imaging with [^99mTc]Tc-HYNFA via folate receptor (FR) targeting was proposed to assess the inflammation and therapeutic effect of systemic sclerosis (SSc) in model mice. The radiochemical yield and purity of [^99mTc]Tc-HYNFA were over 95%, with a specific activity of about 9.36 ± 0.17 MBq/nmol. At the end of induction, the uptake ratios of bleomycin-injected regions on the back-to-muscle (R/M) and lung-to-muscle (L/M) derived from SPECT images were 7.27 ± 0.50 and 4.25 ± 0.15, respectively. The radioactivity uptakes could be blocked by excessive folic acid (FA), and R/M and L/M obviously decreased to 2.78 ± 0.57 and 2.51 ± 0.79, respectively. R/M (2.22 ± 0.71) and L/M (1.62 ± 0.28) decreased very close to those of the control mice group (R/M = 1.99 ± 0.36, L/M = 1.50 ± 0.14) when macrophages had been depleted in advance. After being treated with cyclophosphamide (CTX) or methotrexate (MTX), R/M and L/M decreased to 3.58 ± 0.52 and 2.03 ± 0.32 (CTX treatment) or 2.48 ± 0.64 and 1.83 ± 0.06 (MTX treatment). R/M and L/M were highly correlated with pathological changes. The trend of hydroxyproline content in lungs at the later non-inflammatory phase of each group was similar to the uptake values of the lung in the 4th week from the beginning of induction. [^99mTc]Tc-HYNFA had an ideal uptake in SSc lesions. R/M and L/M had a high consistency with pathological changes. SPECT imaging-targeted FR could monitor the therapeutic effect of CTX and MTX. It is expected to be an effective means to evaluate SSc.