{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T01:15:35Z","timestamp":1791249335178,"version":"4.1.0"},"reference-count":19,"publisher":"BMJ","issue":"8","license":[{"start":{"date-parts":[[2022,8,23]],"date-time":"2022-08-23T00:00:00Z","timestamp":1661212800000},"content-version":"unspecified","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["80-87700-98-22190"],"award-info":[{"award-number":["80-87700-98-22190"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]},{"name":"PentixaPharm GmbH","award":["N\/a"],"award-info":[{"award-number":["N\/a"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2022,7,22]]},"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Primary aldosteronism (PA) is the most common form of secondary hypertension. It is caused by overproduction of aldosterone by either a unilateral aldosterone-producing adenoma (APA) or by bilateral adrenal hyperplasia (BAH). Distinction is crucial, because PA is cured by adrenalectomy in APA and is treated by mineralocorticoid receptor antagonists in BAH. The distinction is currently made by adrenal vein sampling (AVS). AVS is a costly, invasive and complex technical procedure with limited availability and is not superior in terms of outcomes to CT scan-based diagnosis. Thus, there is a need for a cheaper, non-invasive and readily available diagnostic tool in PA. We propose a new diagnostic imaging modality employing the positron emission tomography (PET) tracer [\n                      <jats:sup>68<\/jats:sup>\n                      Ga]Ga-PentixaFor. This tracer has high focal uptake in APAs, whereas low uptake was shown in patients with normal adrenals. Thus, [\n                      <jats:sup>68<\/jats:sup>\n                      Ga]Ga-PentixaFor PET\/CT is an imaging modality with the potential to improve subtyping of PA. It is readily available, safe and, as an out-patient procedure, much cheaper diagnostic method than AVS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>\n                      We present a two-step randomised controlled trial (RCT) protocol in which we assess the accuracy of [\n                      <jats:sup>68<\/jats:sup>\n                      Ga]Ga-PentixaFor PET\/CT in the first step and compare [\n                      <jats:sup>68<\/jats:sup>\n                      Ga]Ga-PentixaFor PET\/CT to AVS in the second step. In the first step, the concordance will be determined between [\n                      <jats:sup>68<\/jats:sup>\n                      Ga]Ga-PentixaFor PET\/CT and AVS and a concordance probability is calculated with a Bayesian prediction model. In the second step, we will compare [\n                      <jats:sup>68<\/jats:sup>\n                      Ga]Ga-PentixaFor PET\/CT and AVS for clinical outcome and intensity of hypertensive drug use defined as daily defined doses in a RCT.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>Ethics approval was acquired from the medical ethical committee East-Netherlands (METC Oost-Nederland). Results will be disseminated through peer-reviewed articles.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>NL9625.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2022-060779","type":"journal-article","created":{"date-parts":[[2022,8,23]],"date-time":"2022-08-23T12:22:32Z","timestamp":1661257352000},"page":"e060779","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":20,"title":["CXCR4-directed [\n                    <sup>68<\/sup>\n                    Ga]Ga-PentixaFor PET\/CT versus adrenal vein sampling performance: a study protocol for a randomised two-step controlled diagnoStic Trial Ultimately comparing hypertenSion outcome in primary aldosteronism (CASTUS)"],"prefix":"10.1136","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7975-8484","authenticated-orcid":false,"given":"Amir Hossein","family":"Chaman Baz","sequence":"first","affiliation":[{"name":"Urology, Radboudumc, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elle","family":"van de Wiel","sequence":"additional","affiliation":[{"name":"Urology, Radboudumc, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Groenewoud","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Biostatistics and Health Technology Assessment, Radboud University Medical Center, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Arntz","sequence":"additional","affiliation":[{"name":"Radiology, Radboudumc, Nijmegen, Gelderland, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Gotthardt","sequence":"additional","affiliation":[{"name":"Nuclear Medicine, Radboudumc, Nijmegen, Gelderland, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaap","family":"Deinum","sequence":"additional","affiliation":[{"name":"Internal Medicine, Radboudumc, Nijmegen, Gelderland, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Langenhuijsen","sequence":"additional","affiliation":[{"name":"Urology, Radboudumc, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2022,8,23]]},"reference":[{"key":"2025120617525275000_12.8.e060779.1","doi-asserted-by":"publisher","DOI":"10.3399\/bjgp18X694589"},{"key":"2025120617525275000_12.8.e060779.2","unstructured":"Prevalentie hypertensie in huisartsenpraktijk: Volksgezondheid en Zorg, 2019. Available: https:\/\/www.volksgezondheidenzorg.info\/onderwerp\/bloeddruk\/cijfers-context\/huidige-situatie"},{"key":"2025120617525275000_12.8.e060779.3","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/S2213-8587(17)30319-4","article-title":"Cardiovascular events and target organ damage in primary aldosteronism compared with essential hypertension: a systematic review and meta-analysis","volume":"6","author":"Monticone","year":"2018","journal-title":"Lancet Diabetes Endocrinol"},{"key":"2025120617525275000_12.8.e060779.4","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1210\/jc.2017-01442","article-title":"Quality of life in primary aldosteronism: a comparative effectiveness study of adrenalectomy and medical treatment","volume":"103","author":"Velema","year":"2018","journal-title":"J Clin Endocrinol Metab"},{"key":"2025120617525275000_12.8.e060779.5","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2015-4061"},{"key":"2025120617525275000_12.8.e060779.6","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1001\/jamacardio.2018.2003","article-title":"Incidence of atrial fibrillation and mineralocorticoid receptor activity in patients with medically and surgically treated primary aldosteronism","volume":"3","author":"Hundemer","year":"2018","journal-title":"JAMA Cardiol"},{"key":"2025120617525275000_12.8.e060779.7","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013-4146"},{"key":"2025120617525275000_12.8.e060779.8","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2007-2055"},{"key":"2025120617525275000_12.8.e060779.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.surg.2004.06.051"},{"key":"2025120617525275000_12.8.e060779.10","unstructured":"George P , Chrousos AS , Kyritsi EM . Hyperaldosteronism workup, 2020. Available: https:\/\/emedicine.medscape.com\/article\/920713-workup#c8"},{"key":"2025120617525275000_12.8.e060779.11","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/S2213-8587(16)30100-0","article-title":"Adrenal vein sampling versus CT scan to determine treatment in primary aldosteronism: an outcome-based randomised diagnostic trial","volume":"4","author":"Dekkers","year":"2016","journal-title":"Lancet Diabetes Endocrinol"},{"key":"2025120617525275000_12.8.e060779.12","doi-asserted-by":"crossref","DOI":"10.1007\/s00259-022-05849-y","article-title":"CXCR4-targeted theranostics in oncology","author":"Buck","year":"2022","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"2025120617525275000_12.8.e060779.13","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1161\/HYPERTENSIONAHA.117.09975","article-title":"Targeting CXCR4 (CXC chemokine receptor type 4) for molecular imaging of aldosterone-producing adenoma","volume":"71","author":"Heinze","year":"2018","journal-title":"Hypertension"},{"key":"2025120617525275000_12.8.e060779.14","doi-asserted-by":"crossref","first-page":"2656","DOI":"10.1007\/s00259-020-04722-0","article-title":"Imaging CXCR4 expression in patients with suspected primary hyperaldosteronism","volume":"47","author":"Ding","year":"2020","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"2025120617525275000_12.8.e060779.15","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1016\/S2213-8587(17)30135-3","article-title":"Outcomes after adrenalectomy for unilateral primary aldosteronism: an international consensus on outcome measures and analysis of remission rates in an international cohort","volume":"5","author":"Williams","year":"2017","journal-title":"Lancet Diabetes Endocrinol"},{"key":"2025120617525275000_12.8.e060779.16","doi-asserted-by":"crossref","first-page":"205031211667172","DOI":"10.1177\/2050312116671725","article-title":"Sf-36 total score as a single measure of health-related quality of life: Scoping review","volume":"4","author":"Lins","year":"2016","journal-title":"SAGE Open Med"},{"key":"2025120617525275000_12.8.e060779.17","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1530\/EC-19-0026","article-title":"A disease-specific quality of life questionnaire for primary aldosteronism","volume":"8","author":"Velema","year":"2019","journal-title":"Endocr Connect"},{"key":"2025120617525275000_12.8.e060779.18","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1016\/S2213-8587(17)30135-3","article-title":"Outcomes after adrenalectomy for unilateral primary aldosteronism: an international consensus on outcome measures and analysis of remission rates in an international cohort","volume":"5","author":"Williams","year":"2017","journal-title":"Lancet Diabetes Endocrinol"},{"key":"2025120617525275000_12.8.e060779.19","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-151-5-200909010-00007"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2022-060779","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,7]],"date-time":"2025-12-07T01:52:58Z","timestamp":1765072378000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2022-060779"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8]]},"references-count":19,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2022,8,23]]},"published-print":{"date-parts":[[2022,8]]}},"alternative-id":["10.1136\/bmjopen-2022-060779"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2022-060779","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8]]}}}