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Here, we synthesized a bone pH sensor by labeling alendronate with the H+\u2010sensitive dye fluorescein isothiocyanate (Aln\u2010FITC). Aln\u2010FITC showed selective affinity for hydroxyapatite (HAp) rather than other calcium materials. An in vivo biodistribution study showed that Aln\u2010FITC can be rapidly and specifically delivered to rat bones after caudal vein injection, and the fluorescence lasted for at least 12\u2009h. The fluorescence intensity of Aln\u2010FITC binding to HAp linearly decreased when the pH changed from 6 to 12. This finding was further confirmed on bone blocks and perfused bone when the pH changed from 6.8 to 7.4, indicating unique pH\u2010responsive characteristics in the bone microenvironment. Aln\u2010FITC was then preliminarily applied to evaluate the changes in bone pH in a nude mouse acidosis model. Our results demonstrated that Aln\u2010FITC might have the potential for minimally invasive and real\u2010time in vivo bone pH sensing in preclinical studies of bone healing, metabolism, and cancer mechanisms.<\/jats:p>","DOI":"10.1155\/2020\/4012194","type":"journal-article","created":{"date-parts":[[2020,5,20]],"date-time":"2020-05-20T23:34:18Z","timestamp":1590017658000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["FITC\u2010Labeled Alendronate as an In Vivo Bone pH Sensor"],"prefix":"10.1155","volume":"2020","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1768-1140","authenticated-orcid":false,"given":"Yuzhou","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiru","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0224-6640","authenticated-orcid":false,"given":"Jinlin","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3274-7550","authenticated-orcid":false,"given":"Sheng","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,5,20]]},"reference":[{"key":"e_1_2_9_1_2","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/138.2.415S"},{"key":"e_1_2_9_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.820281209"},{"key":"e_1_2_9_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrep.2017.02.001"},{"key":"e_1_2_9_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.10050"},{"key":"e_1_2_9_5_2","doi-asserted-by":"publisher","DOI":"10.3892\/or.2016.4997"},{"key":"e_1_2_9_6_2","first-page":"5670","article-title":"Noninvasive measurement of interstitial pH profiles in normal and neoplastic tissue using fluorescence ratio imaging microscopy","volume":"54","author":"Martin G. 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