A Novel Radioimmune 99mTc-Labeled Tracer for Imaging Sphingosine 1-Phosphate Receptor 1 in Tumor Xenografts: An In Vitro and In Vivo Study.
Sphingosine-1-phosphate (S1P) is a phospholipid that regulates pleiotropic biological activities and exerts extracellular functions by binding to five specific G-protein-coupled receptors, S1P receptors (S1PR) 1-5. When activated by S1P, S1PR promote the proliferation and invasion of tumor cells by inducing the formation of new blood vessels. We developed and assessed a new monoclonal antibody imaging probe 99mTc-HYNIC-S1PR1mAb, to explore the feasibility of targeting the S1PR1 in vitro and in vivo. S1PR1mAb was prepared and followed by technetium-99m labeling with succinimidyl 6-hydraziniumnicotinate hydrochloride. Cell uptake and blocking studies were performed to investigate the binding specificity of 99mTc-HYNIC-S1PR1mAb in vitro. 99mTc-HYNIC-S1P1mAb was also tested in vivo in mice xenografted with SK-HEP-1 (high-expression of S1PR1) and MCF-7 (low-expression of S1PR1) using single-photon emission-computed tomography (SPECT). Ex vivo gamma counting of tissues from tumor-bearing mice was used to evaluate 99mTc-HYNIC-S1PR1mAb biodistribution. The biodistribution study results showed significantly higher uptake in SK-HEP-1 tumors than in MCF-7 tumors (P < 0.001). Reduced uptake of 99mTc-HYNIC-S1PR1mAb in SK-HEP-1 was observed in tumor-bearing nude mice pretreated with fingolimod, which binds competitively to the receptors, especially S1PR1. 99mTc-HYNIC-S1PR1mAb can be synthesized and specifically targeted to S1PR1 in vitro and in vivo, allowing S1PR1 expression assessment with SPECT imaging.
['Ye|Min|M|', 'Gai|Yongkang|Y|', 'Ji|Hao|H|', 'Jiang|Yaqun|Y|', 'Qiao|Pengxin|P|', 'Wang|Wenxia|W|', 'Zhang|Yongxue|Y|', 'Xia|Xiaotian|X|', 'Lan|Xiaoli|X|']
D000818:Animals D000911:Antibodies, Monoclonal D001692:Biological Transport D045744:Cell Line, Tumor D005260:Female D064593:Heterografts D006801:Humans D061986:MCF-7 Cells D051379:Mice D008807:Mice, Inbred BALB C D008819:Mice, Nude D011849:Radioactive Tracers D000081025:Sphingosine-1-Phosphate Receptors D013667:Technetium D014018:Tissue Distribution D015899:Tomography, Emission-Computed, Single-Photon D023041:Xenograft Model Antitumor Assays
radioimmune 99mTc-HYNIC-S1PR1mAb SK-HEP-1 SPECT MCF-7 (breast cancer) sphingosin-1-phosphate receptor 1 sphingosine-1 phosphate