文摘
Purpose Follicle-stimulating hormone receptor (FSHR) is overexpressed in primary and metastatic tumor. Molecular imaging of FSHR is beneficial for prognosis and therapy of cancer. FSHβ(33-3) (YTRDLVYKDPARPKIQKTCTF), denoted as FSH1, is a FSHR antagonist. In the present study, maleimide-NOTA conjugate of FSH1 (NOTA-MAL-FSH1) was designed and labeled with [18F] aluminum fluoride. The resulting tracer, 18F-Al-NOTA-MAL-FSH1, was preliminarily evaluated in PET imaging of FSHR-positive tumor. Procedures NOTA-MAL-FSH1 was synthesized and radiolabeled with Al18F complex. The tumor-targeting potential and pharmacokinetic profile of the 18F-labeled compound were evaluated in vitro and in vivo using a PC3 human prostate tumor model. Results 18F-Al-NOTA-MAL-FSH1 can be efficiently produced within 30?min with a non-decay-corrected yield of 48.6?±-.1?% and a radiochemical purity of more than 95?%. The specific activity was at least 30?GBq/μmol. The radiotracer was stable in phosphate-buffered saline and human serum for at least 2?h. The IC50 values of displacement 18F-Al-NOTA-MAL-FSH1 with FSH1 were 252?±-.12?nM. The PC3 human prostate tumor xenografts were clearly visible with high contrast after injection of 18F-Al-NOTA-MAL-FSH1 via microPET. At 30, 60 and 120?min postinjection, the tumor uptakes were 2.98?±-.29?% injected dose (ID)/g, 2.53?±-.20?%ID/g and 1.36?±-.12?%ID/g, respectively. Dynamic PET scanning showed that tumor uptake reached a plateau by about 6?min. Heart peaked earlier and then cleared quickly. Biodistribution studies confirmed that the normal organs except kidney uptakes were all below 1?%ID/g at 1?h p.i. The tumor-to-blood and tumor-to-muscle ratio at 10?min, 0.5, 1, and 2?h after injection were 1.64?±-.36, 2.97?±-.40, 9.31?±-.06, and 13.59?±-.33 and 7.05?±-.10, 10.10?±-.48, 16.17?±-.29, and 30.88?±-.67, respectively. The tracer was excreted mainly through the renal system, as evidenced by high levels of radioactivity in the kidneys. FSHR-binding specificity was also demonstrated by reduced tumor uptake of 18F-Al-NOTA-MAL-FSH1 after coinjection with an excess of unlabeled FSH1 peptide. Conclusion NOTA-MAL-FSH1 could be labeled rapidly and efficiently with 18F using one step method. Favorable preclinical data suggest that 18F-Al-NOTA-MAL-FSH1 may be a suitable radiotracer for the non-invasive visualization of FSHR positive tumor in vivo.