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The DAT is expressed not only at the plasma membrane of dopaminergic neurons, but is also trafficking within the cytoplasm. It has been well documented that the striatal [\n                    <jats:sup>123<\/jats:sup>\n                    I]I-FP-CIT binding is lower in disorders neuropathologically characterized by DAT loss induced by degeneration of nigrostriatal dopaminergic neurons (e.g., Parkinson\u2019s disease).\n                    <jats:italic>In addition<\/jats:italic>\n                    , in studies in subjects without dopaminergic degeneration it has been suggested that\n                    <jats:italic>subtle<\/jats:italic>\n                    lower striatal binding can be induced by down-regulation of the DAT. However, theoretically, down-regulation can only be measured if [\n                    <jats:sup>123<\/jats:sup>\n                    I]I-FP-CIT binds predominantly to the DAT expressed at the plasma membrane, but not due to binding to the internalized DAT. We therefore looked into the literature to find support or opposition for this postulate. In this brief narrative review, we found indirect evidence that tracers like [\n                    <jats:sup>123<\/jats:sup>\n                    I]I-FP-CIT binds predominantly to the DAT expressed on plasma membrane of nigrostriatal dopaminergic neurons.\n                  <\/jats:p>","DOI":"10.1007\/s12149-025-02140-6","type":"journal-article","created":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T10:15:56Z","timestamp":1765016156000},"page":"101-107","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The radiotracer [123I]I-FP-CIT binds preferentially to the dopamine transporter expressed at the plasma membrane of nigrostriatal dopaminergic neurons: a new concept"],"prefix":"10.1007","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6378-7638","authenticated-orcid":false,"given":"Jan","family":"Booij","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6223-3454","authenticated-orcid":false,"given":"Youssef","family":"Chahid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2258-5639","authenticated-orcid":false,"given":"Eric A.","family":"Reits","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0020-3807","authenticated-orcid":false,"given":"Ulrik","family":"Gether","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,6]]},"reference":[{"key":"2140_CR1","doi-asserted-by":"publisher","first-page":"S27","DOI":"10.2967\/jnumed.121.263197","volume":"63","author":"ED Wallert","year":"2022","unstructured":"Wallert ED, van de Giessen E, Knol RJJ, Beudel M, de Bie RMA, Booij J. 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