Evaluation of [68Ga]Ga-PentixaFor PET Imaging for the Identification of Unilateral Adrenal Secretion of ALdosterON in Patients With Primary Aldosteronism

Официальное название

"Pilot Study for the Evaluation of [68Ga]Ga-PentixaFor PET Imaging for the Identification of Unilateral Adrenal Secretion of ALdosterON in Patients With Primary Aldosteronism"

Обзор

PentixaFor radiolabeled with 68Gallium (68Ga) is a radiopharmaceutical targeting the CXC chemokine receptor 4 (CXCR4) receptor. The CXCR4 receptor is expressed in zona glomerulosa of the adrenal cortex and in aldosterone producing adenoma (APA). The objective of this study will be to evaluate in 25 patients if \[68Ga\]Ga-PentixaFor positron emission tomography (\[68Ga\]Ga-PTF-PET) imaging allows for the discrimination of patients with lateralized or non-lateralized secretion of aldosterone in adrenal glands classified based on adrenal vein sampling (AVS).

Подробное описание

The identification of the cause of primary aldosteronism (PA) is critical because, in case of lateralized secretion of aldosterone, a surgical treatment can be offered to patients with the objective of full patient recovery, whereas in case of bilateral secretion, only a long-term medical treatment with mineralocorticoid receptor antagonists should be considered. The presence or absence of adrenal nodule on morphological imaging does not allow us to state on the lateralization or not of aldosterone secretion. Moreover, on one hand, the prevalence of adrenal incidentalomas, mostly non-secreting, can be detected in between 2 to 10% of general population. On the other hand, unilateral secretion of aldosterone exists in 30% of patients with normal adrenal glands on imaging. The AVS with measurements of the concentrations of aldosterone is the closest to a referral exam to confirm the diagnosis of lateralized secretion of aldosterone, but it is a complex and invasive procedure with only limited access to centers with expertise in invasive radiology and an important heterogeneity in interpretation. The development of noninvasive imaging approaches allowing for a more specific identification of lateralized vs. bilateral aldosterone secretion would, hence, have a major impact on the clinical management of these patients.

Вмешательства

• Комбинированный продукт [68Ga]Ga-PentixaFor PET imaging
  PET imaging of adrenal glands

Первичные конечные точки

• relevant biomarkers strongly associated with primary lateralized hyperaldosteronism [Срок оценки: 30 days after inclusion]

Вторичные конечные точки (9)

• Aldosterone-to-cortisol ratio between the two adrenal veins on AVS [Срок оценки: at inclusion]
• Lateralization index during AVS [Срок оценки: at baseline (during AVS day)]
• Ratio between the highest SUVmax among both adrenal glands and mean SUV of the liver on [68Ga]Ga-PTF-PET imaging [Срок оценки: 30 days after inclusion]
• Proportion of patients with persistence of PA [Срок оценки: 6 months after surgical adrenalectomy]
• CXCR4 expression levels by immuno-histology highest CXCR4 density [Срок оценки: 6 months after surgical adrenalectomy]
• Adenoma size on CT [Срок оценки: 30 days after inclusion]
• Adenoma size on histology [Срок оценки: 6 months after surgical adrenalectomy]
• Incidence of Treatment Emergent Adverse Events after [68Ga]Ga-PentixaFor injection (tolerability) [Срок оценки: 30 days after [68Ga]Ga-PentixaFor injection]
• Incidence of Treatment Emergent Serious Adverse Events after [68Ga]Ga-PentixaFor injection (Safety) [Срок оценки: 12 months after [68Ga]Ga-PentixaFor injection]

Критерии участия

Критерии включения

• Age ≥ 18 years old
• Signed written informed consent
• French Social Security affiliation
• For child-bearing aged women, effective form of contraception\*
• Diagnosis of primary aldosteronism:
• With or without adrenal nodule on morphological imaging (CT or Magnetic Resonance Imaging)
• With unilateral or bilateral aldosterone secretion confirmed by invasive AVS

• Such methods include: combined hormonal contraception, progestogen-only hormonal contraception, intrauterine device (IUD) or hormone-releasing system (IUS), bilateral tubal occlusion, vasectomised partner, condom, sexual abstinence.

Критерии исключения

• Pregnant or breastfeeding women
• Patient under legal protection (guardianship)
• Contraindication to the PET-CT
• Contraindication to the injection of \[68Ga\]Ga-PentixaFor
• Participation in another interventional study involving human participants or being in the exclusion period at the end of a previous study involving human participants, if applicable
• Patient on AME (state medical aid) (unless exemption from affiliation)
• Completed group: if the expected number of patients has been reached (15 patients) in the corresponding group of patients (with lateralized or non-lateralized PA).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Диагностика

Центры проведения

Франция · 2 центра

• hôpital Cochin — Paris
• Hôpital européen Georges Pompidou - APHP — Paris

Публикации

• Mulatero P, Monticone S, Deinum J, Amar L, Prejbisz A, Zennaro MC, Beuschlein F, Rossi GP, Nishikawa T, Morganti A, Seccia TM, Lin YH, Fallo F, Widimsky J. Genetics, prevalence, screening and confirmation of primary aldosteronism: a position statement and consensus of the Working Group on Endocrine Hypertension of The European Society of Hypertension. J Hypertens. 2020 Oct;38(10):1919-1928. doi: 1 PMID 32890264
• Amar L, Baguet JP, Bardet S, Chaffanjon P, Chamontin B, Douillard C, Durieux P, Girerd X, Gosse P, Hernigou A, Herpin D, Houillier P, Jeunemaitre X, Joffre F, Kraimps JL, Lefebvre H, Menegaux F, Mounier-Vehier C, Nussberger J, Pagny JY, Pechere A, Plouin PF, Reznik Y, Steichen O, Tabarin A, Zennaro MC, Zinzindohoue F, Chabre O. SFE/SFHTA/AFCE primary aldosteronism consensus: Introduction and handb PMID 27315757
• Mulatero P, Sechi LA, Williams TA, Lenders JWM, Reincke M, Satoh F, Januszewicz A, Naruse M, Doumas M, Veglio F, Wu VC, Widimsky J. Subtype diagnosis, treatment, complications and outcomes of primary aldosteronism and future direction of research: a position statement and consensus of the Working Group on Endocrine Hypertension of the European Society of Hypertension. J Hypertens. 2020 Oct;38(10): PMID 32890265
• Hyafil F, Pelisek J, Laitinen I, Schottelius M, Mohring M, Doring Y, van der Vorst EP, Kallmayer M, Steiger K, Poschenrieder A, Notni J, Fischer J, Baumgartner C, Rischpler C, Nekolla SG, Weber C, Eckstein HH, Wester HJ, Schwaiger M. Imaging the Cytokine Receptor CXCR4 in Atherosclerotic Plaques with the Radiotracer 68Ga-Pentixafor for PET. J Nucl Med. 2017 Mar;58(3):499-506. doi: 10.2967/jnumed.1 PMID 27789718
• Bluemel C, Hahner S, Heinze B, Fassnacht M, Kroiss M, Bley TA, Wester HJ, Kropf S, Lapa C, Schirbel A, Buck AK, Herrmann K. Investigating the Chemokine Receptor 4 as Potential Theranostic Target in Adrenocortical Cancer Patients. Clin Nucl Med. 2017 Jan;42(1):e29-e34. doi: 10.1097/RLU.0000000000001435. PMID 27819856
• Heinze B, Fuss CT, Mulatero P, Beuschlein F, Reincke M, Mustafa M, Schirbel A, Deutschbein T, Williams TA, Rhayem Y, Quinkler M, Rayes N, Monticone S, Wild V, Gomez-Sanchez CE, Reis AC, Petersenn S, Wester HJ, Kropf S, Fassnacht M, Lang K, Herrmann K, Buck AK, Bluemel C, Hahner S. Targeting CXCR4 (CXC Chemokine Receptor Type 4) for Molecular Imaging of Aldosterone-Producing Adenoma. Hypertension. PMID 29279316
• Kempers MJ, Lenders JW, van Outheusden L, van der Wilt GJ, Schultze Kool LJ, Hermus AR, Deinum J. Systematic review: diagnostic procedures to differentiate unilateral from bilateral adrenal abnormality in primary aldosteronism. Ann Intern Med. 2009 Sep 1;151(5):329-37. doi: 10.7326/0003-4819-151-5-200909010-00007. PMID 19721021
• Sam D, Kline GA, So B, Leung AA. Discordance Between Imaging and Adrenal Vein Sampling in Primary Aldosteronism Irrespective of Interpretation Criteria. J Clin Endocrinol Metab. 2019 Jun 1;104(6):1900-1906. doi: 10.1210/jc.2018-02089. PMID 30590677

Идентификаторы

NCT: NCT06478875 · APHP220881 · 2023-505507-22-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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