INTRODUCTION

Despite many advances in diagnosis and treatment of Cushing’s syndrome (CS) remains one of the key challenges of endocrinology in the 21st century [1]. Despite its low incidence (approximately 2–3 cases per million person-years), endogenous CS is often over-investigated because obesity, hypertension, and metabolic syndrome are common in the general population [2].

If suspected, CS is confirmed biochemically using one of the three established screening tests, urinary free cortisol (UFC), overnight dexamethasone suppression test and late-night salivary cortisol. Measurement of plasma adrenocorticotropic hormone (ACTH) distinguishes ACTH-independent (adrenal) CS from ACTH-dependent causes—Cushing’s disease (CD) and ectopic/paraneoplastic Cushing’s syndrome (ECS) [3].

Imaging, such as high-resolution magnetic resonance imaging (MRI) and thin-sliced computed tomography (CT), is used to clarify the origin of hypercortisolism, once biochemical testing has narrowed down the source of CS to either adrenal, pituitary and/or ECS. Especially the separation from CD and ECS can be challenging, since in both entities the tumor may be invisible by conventional imaging. In such instances, inferior petrosal sinus sampling (IPSS) is used [4] to confirm the pituitary origin of ACTH excess [1,3,5].

In case of CD, acquiring high-resolution thin-section images is of critical importance, particularly in diagnosing microadenomas. ACTH-secreting microadenomas (<1.0 cm) are typically small lesions more than 6 mm in diameter that can be visualized by 1.5 and 3.0 T gadolinium-enhanced MRI. Owing to its advantageous soft tissue contrast, MRI is the primary imaging technique used for the diagnosis of corticotroph tumors [4,6]. In a contemporary cohort, more than 70% had definite or probable abnormal MRI findings [7].

Positron emission tomography (PET) is recently gaining increasing importance in managing pituitary diseases [8,9]. Molecular and functional imaging—long established in other neuroendocrine tumors—can provide essential diagnostic information and, in selected patients, guide treatment decisions by delineating tumor receptor expression levels and altered metabolic pathways [10].

The biologic principle of PET imaging is based on corticotroph tumor metabolism and receptor expression, which is based on increased protein synthesis, hormone production, and glucose metabolism. These tumor specific features can be identified using specific radiopharmaceuticals, ideally in an early stage, even before becoming detectable by conventional imaging [11]. While PET images from PET/CT scanners can be merged with MRI data after PET acquisition, image acquisition with a PET/MRI device is advantageous, due to the reduced risk of misalignment between PET and MRI. For a successful coregistration of PET and MRI, a three-dimensional MRI with an extended field of view over the complete skull is useful. These MRI sequences are often not acquired in standard sella MRI protocols.

This article presents a focused literature review with a comprehensive analysis of the most commonly used radiotracers. Special emphasis is placed on recent advances and emerging radiotracers that are likely to reshape the diagnosis and management of CD.

METHODS AND SEARCH STRATEGY

This is a narrative review conducted in August 2025. Inclusion criteria were: (1) English language articles; (2) publication dates from January 1, 2000, to August 31, 2025; (3) original studies and reviews addressing PET/CT and PET/MRI in diagnosis of CD. Non-English articles were excluded. Retrieved articles were selected and analyzed for information on PET in pituitary disease.

RESULTS

[¹⁸F]fluorodeoxyglucose PET

[¹⁸F]fluorodeoxyglucose ([¹⁸F]FDG)-PET is an essential cornerstone in the work-up, diagnostic staging, and treatment evaluation of cancer [12–14]. Firmly established as an indispensable tool in a broad spectrum of solid and hematologic neoplasia, its role in pituitary adenomas is less well defined. In general, the physiological radiotracer uptake of the [¹⁸F]FDG in the pituitary gland is low [15]. Few studies reported an elevated [¹⁸F]FDG uptake in functional and non-functional pituitary adenomas, in hypophysitis and metastatic lesions of the pituitary [15–17]. An incidentally increased pituitary [¹⁸F]FDG uptake on PET was found in only 30 of 40,967 whole body [¹⁸F]FDG-PET scans (0.073%). Nineteen of these 30 patients underwent MRI, which showed a pituitary adenoma in 18/19 cases (94.7%). The intensity of the radiotracer uptake correlated with the adenoma size on MRI [15]. Histological diagnosis was obtained in three patients and included two growth hormone-secreting adenomas and one non-functioning adenoma [15].

[¹⁸F]FDG-PET has been also used for diagnosis of CD, with limited success (Table 1) [18–25]. In one of the first studies, [¹⁸F]FDG-PET was positive in seven of the 12 cases of CD (sensitivity 58%), not superior to pituitary MRI [18]. Subsequent studies found similarly low detection rates with 40% [20]. One study analyzed the effect of corticotropin-releasing hormone (CRH) stimulation on detection rates of corticotropinoma during [¹⁸F]FDG-PET. This study reported that intravenous CRH stimulation may lead to increased [¹⁸F]FDG uptake, and a limited increase in the rate of detection of corticotropinomas in

CD. However, the overall detection rate (sensitivity) remained at 59% with CRH stimulation [24]. In summary, [¹⁸F]FDG-PET appears to be of limited use in the visualization of corticotropinomas.

Somatostatin receptor based PET ([⁶⁸Ga]Ga-DOTATATE, [⁶⁸Ga]Ga-DOTANOC, and [⁶⁸Ga]Ga-DOTATOC)

Radiolabeled somatostatin analogues such as [⁶⁸Ga]Gallium-labeled DOTA-Tyr3-octreotate ([⁶⁸Ga]Ga-DOTATATE), [⁶⁸Ga] Gallium-labeled DOTA-Tyr3-octreotide ([⁶⁸Ga] Ga-DOTATOC), and [⁶⁸Ga]Gallium-labeled DOTA-1-Nal(3)-octreotide ([⁶⁸Ga]Ga-DOTANOC) are firmly established PET radiopharmaceuticals to diagnose neuroendocrine tumors based on somatostatin receptor (SSTR) expression. In all three compounds octreotide is conjugated to the [⁶⁸Ga]Ga-DOTA (tetraazacyclododecane-1,4,7,10-tetraacetic acid). Accordingly, they are suited for the detection of tumors causing ECS. They represent modified octreotide molecules combined with the radioactive gallium-68 isotope, which bind to SSTRs with an affinity similar to octreotide [3]. The different SSTR-targeting PET tracers show a varying binding profile to the SSTR-subtypes: [⁶⁸Ga]Ga-DOTATOC shows a high affinity to SSTR2 and a moderate affinity to SSTR5 and [⁶⁸Ga]Ga-DOTANOC a high affinity for SSTR2, SSTR3, and SSTR5. [⁶⁸Ga]Ga-DOTATATE shows a ten-fold stronger affinity to SSTR2 receptors than [⁶⁸Ga]Ga-DOTATOC and [⁶⁸Ga]Ga-DOTATOC, but almost no binding to SSTR5 [26]. While the healthy pituitary predominantly expresses SSTR2 and SSTR5, corticotroph tumors predominantly express SSTR5 followed by SSTR2. To our knowledge, there are no studies comparing the tracer avidity of different SSTR-targeting radiotracers in corticotroph adenoma. Available studies on SSTR imaging in corticotroph tumors is summarized in the following [26]: In a recent prospective head-to-head comparison of [⁶⁸Ga]Ga-DOTATATE PET with [¹⁸F]DOPA PET in 24 patients with the ECS from neuroendocrine tumors, which were confirmed by pathology and biochemical cure, [⁶⁸Ga]Ga-DOTATATE PET had a similar sensitivity as [¹⁸F]DOPA PET (sensitivity of 79% [95% confidence interval, 57%–92%] vs. 88% [95% confidence interval, 67%–97%]) [27]. However, the high SSTR uptake of the pituitary gland makes it difficult to delineate pathological uptake of a pituitary adenoma. In line with this, Tjornstrand et al. [28] and Wang et al. [22] reported a lower [⁶⁸Ga]Ga-DOTATOC and [⁶⁸Ga]Ga-DOTATATE uptake of corticotroph tumors compared to the uptake of normal pituitary tissue. By using a ratio of [¹⁸F]FDG maximum standardized uptake value (SUNmax) over [⁶⁸Ga]Ga-DOTATATE SUVmax, Wang et al. [22] developed an imaging methodology that resulted in 89% sensitivity and 96% specificity. An in vitro study analyzing the immunohistochemical staining of SSTR1–5 in 88 corticotroph PitNET and 30 biopsies of the nonadenomatous pituitary confirmed a lower SSTR2 and SSTR5 expression in corticotroph PitNETs compared to healthy pituitary tissue [29].

Amino acid PET ([¹¹C]methionine and [¹⁸F]fluorethyltyrosine)

With radiolabeled amino acids, the increased activity of the Ltype amino acid transporter (LAT1) in functional pituitary adenomas can be visualized. Amino acid PET is used primarily for neuro-oncologic imaging due to the favorable tumor-to-background ratio in the brain compared to the standard unspecific oncological tracer [¹⁸F]FDG. Amino acid PET with ¹¹C-methionine has been used for the detection of pituitary adenoma since the early 2000s. Since 2006, multiple small studies have investigated ¹¹C-methionine for the localization of ACTH-producing pituitary adenoma including between eight and 22 patients with PET imaging with first diagnosis or recurrent CD (Table 1) [19,21,30–37]. They found PET-positive lesions in the pituitary of 60% to 100% of included patients. Six studies compared the PET results to intraoperative or histopathologic results and found a correct prediction of the tumor localization in 89% to 100% (Table 1) [30,32–35,37]. Since 2021, two studies explored PET imaging of the pituitary with the fluorine-18 bound radiotracer [¹⁸F]fluorethyltyrosine [32,35]. In comparison to carbon-11, fluorine-18 shows logistic advantages (longer half-time, shorter positron range) and enables a broader availability of the radiotracer. Berkman et al. [32] reported a sensitivity and specificity of 100% of [¹⁸F]FET PET/MRI in comparison with intraoperative and histopathologic findings in nine patients with newly diagnosed corticotroph adenoma. Pruis et al. [35] included 22 MRI-negative patients, 15 of whom underwent surgery, and found a 100% concordance between the [¹⁸F]FET hotspot and the intraoperative findings. In 11 of the 15 operated patients, histopathologic analysis confirmed a corticotroph adenoma, whereas in four cases, the tissue obtained was insufficient for histopathological evaluation.

CXCR4-targeting PET ([⁶⁸Ga]Ga-PentixaFor)

The chemokine C-X-C motif chemokine ligand 12 (CXCL12) and its receptor C-X-C motif chemokine receptor 4 (CXCR4) play a key role in neuroimmune regulation of the anterior pituitary. Both have been implicated in autocrine and paracrine proliferation of pituitary tumor cells, and their overexpression in pituitary adenomas has been proposed as a potential molecular imaging marker [38,39].

The radiotracer [⁶⁸Ga]Ga-PentixaFor, a cyclic pentapeptide with high CXCR4 affinity, was initially used in PET/CT for ACTH-secreting pituitary tumors by Ding et al. [40], demonstrating a detection rate of 85.7% (six of seven cases). In a subsequent study using [⁶⁸Ga]Ga-PentixaFor PET/MRI, sensitivity was 92.7% (38 of 41 cases) [41], increasing to 100% when combined with contrast-enhanced MRI [41]. Among 43 cases, 23 had microadenomas <6 mm, 11 of which were undetectable on MRI. In nine of these, adenomas were confirmed surgically, and biochemical remission was achieved, while the remaining two cases represented false-positive PET/MRI findings. Studies describing PET imaging of the pituitary with [⁶⁸Ga]Ga-PentixaFor are summarized in Table 1 [18–25,28,30–37,40–45].

[⁶⁸Ga]Ga-PentixaFor SUVmax in pituitary CS correlated significantly with serum ACTH and cortisol, 24-hour UFC concentrations, and histologic CXCR4 immunoreactivity [40,41]. Maximum SUVmax was higher in ACTH-secreting pituitary adenomas than in normal pituitary gland and non-functioning adenomas [40,41], and using a PET SUVmax cutoff of 3.0 reliably distinguished ACTH-secreting adenomas from both, achieving 100% sensitivity and specificity [40]. CXCR4 overexpression is not exclusive to corticotropinomas and is also observed in growth hormone-secreting and non-functioning pituitary adenomas, as well as in various normal tissues, including lymph nodes, hematopoietic, and gastrointestinal cells [38,39].

Corticotropin-releasing hormone- and desmopressin-based molecular imaging

CRH is the primary regulator of ACTH secretion from the anterior pituitary, acting mainly through CRH receptor 1 (CRHR1). Both experimental and clinical studies have shown overexpression of CRHR1 in corticotropinomas compared with normal pituitary tissue [46–48]. Despite autonomous ACTH secretion, over 90% of corticotropinomas remain responsive to CRH, as evidenced by increases in plasma ACTH and cortisol following stimulation and by bilateral IPSS.

A novel tracer, [⁶⁸Ga]Ga-DOTA-CRH, in which CRH is conjugated to the [⁶⁸Ga]Ga-DOTA (tetraazacyclododecane-1,4,7,10-tetraacetic acid) has been proposed for imaging CD by targeting CRHR1 on corticotropinomas. In an initial study of 15 patients (six macroadenomas and nine microadenomas, five of which were <6 mm), PET/CT demonstrated 100% sensitivity (Table 1) [42]. In a subsequent study of 24 patients (seven macroadenomas, 17 microadenomas) [⁶⁸Ga]Ga-DOTA-CRH PET/CT achieved 100% diagnostic accuracy. Among these, 10 had microadenomas <6 mm, and in four cases no lesion was detectable on MRI [43]. Fusing [⁶⁸Ga]Ga-DOTA-CRH PET/CT with 3-Tesla MRI facilitated precise intraoperative navigation, accurately localizing tumors even in patients with negative MRI findings. However, high background pituitary uptake due to physiological CRHR1 and R2 expression can impede visualization of microadenomas <6 mm. Moreover, adenomas in the small subset of CD patients (<10%) who are unresponsive to CRH stimulation may not be identified.

Vasopressin 1b (V1b) receptor is strongly expressed in corticotropinomas, in contrast to its basal expression in normal pituitary tissue and minimal expression in other pituitary tumors [48,49]. This is supported by desmopressin-induced ACTH secretion in corticotropinomas, which is absent in healthy individuals and usually also in other conditions such as ECS [49]. Desmopressin binds selectively to the V1b receptor, and [⁶⁸Ga]Ga-mDesmo has been shown to target these receptors in corticotropinomas [50]. In an initial PET/CT study of 24 patients (17 microadenomas, seven macroadenomas), 10 had adenomas <6 mm, eight of which were undetectable or inconclusive on contrast-enhanced MRI; nonetheless, PET accurately localized all adenomas, achieving 100% sensitivity [44]. A major advantage of [⁶⁸Ga]Ga-mDesmo is the absence of physiological pituitary accumulation, reflecting minimal V1b receptor expression in normal pituitary gland [50].

CONCLUSIONS

Molecular imaging is emerging as a promising tool for confirming the presence of a corticotropinoma in patients who have a negative pituitary MRI or an equivocal MRI finding (lesion <6 mm) (Fig. 1). The most promising PET tracers are [¹¹C]methionine, [¹⁸F]fluorethyltyrosine, [⁶⁸Ga]Ga-PentixaFor, [⁶⁸Ga]GamDesmo, and [⁶⁸Ga]Ga-DOTA-CRH. The latter three are currently not widely available. Many pituitary tumors centers of excellence (PTCOE) therefore focus on [¹¹C]methionine and [¹⁸F] fluorethyltyrosine, and large prospective trials are currently under way to confirm the high detection rates described in retrospective and prospective observational studies (e.g., NCT07108244). PET/CT studies can be incorporated into neuronavigation to enable a targeted transsphenoidal surgery. Taken together, the data of molecular imaging could be the missing piece for localizing nearly all corticotropinomas, which will ultimately improve the remission rates of transsphenoidal surgery.

Article information

CONFLICTS OF INTEREST

Martin Reincke reports speaker’s honoraria and consulting by Novartis, Pfizer, Recordati Rare Disease, Ipsen, HRA Pharma, Crinetics, Lundbeck. Jun Thorsteinsdottir reports speaker’s honoraria and consulting by Recordati Rare Disease. Katharina Schilbach received speaker’s honoraria and consulting by Novo Nordisk, Pfizer, Recordati Rare Disease, Ipsen, Crinetics, Ascendis, Camurus and Pharmanovia. The other authors declare no competing interest in relation to this work.

Nathalie L. Albert has received honoraria for lectures, consultation or advisory board participation from ABX, Advanced Accelerator Applications, Carthera, ITM Oncologics, Medsir, Novartis, OncLive, Servier and Telix Pharmaceuticals, and research funding from Novocure, Servier and Telix Pharmaceuticals.

ACKNOWLEDGMENTS

This review has been supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation, Project number: 314061271-TRR 205 to Martin Reincke and Marily Theodoropoulou). Martin Reincke is supported by a grant of the Else Kröner-Fresenius Stiftung in support of the German Cushing’s Registry CUSTODES (2012_A103 and 2015_A228).

Fig. 1

Summary of available radiotracers for positron emission tomography (PET) imaging of the pituitary in Cushing’s disease. CXCR4, C-X-C motif chemokine receptor 4; CRH, corticotropin-releasing hormone; PET, positron emission tomography; CRHR1, corticotropin-releasing hormone receptor 1.

References

• 1. Reincke M, Fleseriu M. Cushing syndrome: a review. JAMA 2023;330:170–81.ArticlePubMed
• 2. Nieman LK, Biller BM, Findling JW, Newell-Price J, Savage MO, Stewart PM, et al. The diagnosis of Cushing’s syndrome: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2008;93:1526–40.ArticlePubMedPMC
• 3. Fleseriu M, Auchus R, Bancos I, Ben-Shlomo A, Bertherat J, Biermasz NR, et al. Consensus on diagnosis and management of Cushing’s disease: a guideline update. Lancet Diabetes Endocrinol 2021;9:847–75.PubMedPMC
• 4. Yang BT, Chong VF, Wang ZC, Xian JF, Chen QH. Sphenoid sinus ectopic pituitary adenomas: CT and MRI findings. Br J Radiol 2010;83:218–24.ArticlePubMedPMC
• 5. Gadelha M, Gatto F, Wildemberg LE, Fleseriu M. Cushing’s syndrome. Lancet 2023;402:2237–52.ArticlePubMed
• 6. Zheng B, Zhao Z, Zheng P, Liu Q, Li S, Jiang X, et al. The current state of MRI-based radiomics in pituitary adenoma: promising but challenging. Front Endocrinol (Lausanne) 2024;15:1426781.ArticlePubMedPMC
• 7. Cristante J, Lefournier V, Sturm N, Passagia JG, Gauchez AS, Tahon F, et al. Why we should still treat by neurosurgery patients with Cushing disease and a normal or inconclusive pituitary MRI. J Clin Endocrinol Metab 2019;104:4101–13.ArticlePubMedPDF
• 8. MacFarlane J, Bashari WA, Senanayake R, Gillett D, van der Meulen M, Powlson AS, et al. Advances in the imaging of pituitary tumors. Endocrinol Metab Clin North Am 2020;49:357–73.ArticlePubMed
• 9. Van Weehaeghe D, Lapauw B, Fraioli F, Cecchin D, Verger A, Guedj E, et al. EANM position on positron emission tomography in suspected functional pituitary neuroendocrine tumours. Eur J Nucl Med Mol Imaging 2024;51:2367–70.ArticlePubMedPDF
• 10. Bashari WA, Senanayake R, Fernandez-Pombo A, Gillett D, Koulouri O, Powlson AS, et al. Modern imaging of pituitary adenomas. Best Pract Res Clin Endocrinol Metab 2019;33:101278.ArticlePubMed
• 11. Bi WL, Laws ER. Metabolic imaging in the detection of growth hormone-secreting pituitary adenomas. World Neurosurg 2014;82:329–30.ArticlePubMed
• 12. Almuhaideb A, Papathanasiou N, Bomanji J. 18F-FDG PET/CT imaging in oncology. Ann Saudi Med 2011;31:3–13.ArticlePubMedPMC
• 13. Boellaard R, Delgado-Bolton R, Oyen WJ, Giammarile F, Tatsch K, Eschner W, et al. FDG PET/CT: EANM procedure guidelines for tumour imaging: version 2.0. Eur J Nucl Med Mol Imaging 2015;42:328–54.PubMed
• 14. Fletcher JW, Djulbegovic B, Soares HP, Siegel BA, Lowe VJ, Lyman GH, et al. Recommendations on the use of 18F-FDG PET in oncology. J Nucl Med 2008;49:480–508.ArticlePubMed
• 15. Jeong SY, Lee SW, Lee HJ, Kang S, Seo JH, Chun KA, et al. Incidental pituitary uptake on whole-body 18F-FDG PET/CT: a multicentre study. Eur J Nucl Med Mol Imaging 2010;37:2334–43.ArticlePubMedPDF
• 16. Stanly A, Sunny SS, Benjamin J, Asha HS, Mathew D, John JR, et al. Utility of F18-FDG PET/CT in the evaluation of pituitary uptake. World J Nucl Med 2024;23:234–41.ArticlePubMedPMC
• 17. Hyun SH, Choi JY, Lee KH, Choe YS, Kim BT. Incidental focal 18F-FDG uptake in the pituitary gland: clinical significance and differential diagnostic criteria. J Nucl Med 2011;52:547–50.ArticlePubMed
• 18. Alzahrani AS, Farhat R, Al-Arifi A, Al-Kahtani N, Kanaan I, Abouzied M. The diagnostic value of fused positron emission tomography/computed tomography in the localization of adrenocorticotropin-secreting pituitary adenoma in Cushing’s disease. Pituitary 2009;12:309–14.ArticlePubMedPDF
• 19. Ikeda H, Abe T, Watanabe K. Usefulness of composite methionine-positron emission tomography/3.0-tesla magnetic resonance imaging to detect the localization and extent of early-stage Cushing adenoma. J Neurosurg 2010;112:750–5.ArticlePubMed
• 20. Chittiboina P, Montgomery BK, Millo C, Herscovitch P, Lonser RR. High-resolution(18)F-fluorodeoxyglucose positron emission tomography and magnetic resonance imaging for pituitary adenoma detection in Cushing disease. J Neurosurg 2015;122:791–7.ArticlePubMedPMC
• 21. Feng Z, He D, Mao Z, Wang Z, Zhu Y, Zhang X, et al. Utility of 11C-methionine and 18F-FDG PET/CT in patients with functioning pituitary adenomas. Clin Nucl Med 2016;41:e130–4.ArticlePubMed
• 22. Wang H, Hou B, Lu L, Feng M, Zang J, Yao S, et al. PET/MRI in the diagnosis of hormone-producing pituitary microadenoma: a prospective pilot study. J Nucl Med 2018;59:523–8.ArticlePubMed
• 23. Zhou J, Ju H, Zhu L, Pan Y, Lv J, Zhang Y. Value of fluorine-18-fluorodeoxyglucose PET/CT in localizing the primary lesion in adrenocorticotropic hormone-dependent Cushing syndrome. Nucl Med Commun 2019;40:539–44.ArticlePubMed
• 24. Boyle J, Patronas NJ, Smirniotopoulos J, Herscovitch P, Dieckman W, Millo C, et al. CRH stimulation improves 18FFDG-PET detection of pituitary adenomas in Cushing’s disease. Endocrine 2019;65:155–65.ArticlePubMedPDF
• 25. Kim K, Kim DK, Moon JH, Kim EH, Kim SH, Ku CR, et al. Dexamethasone suppression for 18F-FDG PET/CT to localize ACTH-secreting pituitary tumors. Cancer Imaging 2023;23:85.ArticlePubMedPMCPDF
• 26. Pauwels E, Cleeren F, Bormans G, Deroose CM. Somatostatin receptor PET ligands: the next generation for clinical practice. Am J Nucl Med Mol Imaging 2018;8:311–31.PubMedPMC
• 27. Elenius H, McGlotten R, Hoang CD, Chen CC, Millo C, Gharib AM, et al. Prospective evaluation of 68Ga-DOTATATE and 18F-DOPA PET scans in detecting tumors causing ectopic ACTH syndrome. J Clin Endocrinol Metab 2025;110:e3794–802.ArticlePubMedPMCPDF
• 28. Tjornstrand A, Casar-Borota O, Heurling K, Scholl M, Gjertsson P, Ragnarsson O, et al. Pre- and postoperative 68 Ga-DOTATOC positron emission tomography for hormone-secreting pituitary neuroendocrine tumours. Clin Endocrinol (Oxf) 2021;94:956–67.ArticlePubMedPDF
• 29. Behling F, Honegger J, Skardelly M, Gepfner-Tuma I, Tabatabai G, Tatagiba M, et al. High expression of somatostatin receptors 2A, 3, and 5 in corticotroph pituitary adenoma. Int J Endocrinol 2018;2018:1763735.ArticlePubMedPMCPDF
• 30. Tang BN, Levivier M, Heureux M, Wikler D, Massager N, Devriendt D, et al. 11C-Methionine PET for the diagnosis and management of recurrent pituitary adenomas. Eur J Nucl Med Mol Imaging 2006;33:169–78.ArticlePubMedPDF
• 31. Koulouri O, Steuwe A, Gillett D, Hoole AC, Powlson AS, Donnelly NA, et al. A role for 11C-methionine PET imaging in ACTH-dependent Cushing’s syndrome. Eur J Endocrinol 2015;173:M107–20.ArticlePubMed
• 32. Berkmann S, Roethlisberger M, Mueller B, Christ-Crain M, Mariani L, Nitzsche E, et al. Selective resection of Cushing microadenoma guided by preoperative hybrid 18-fluoroethyl-L-tyrosine and 11-C-methionine PET/MRI. Pituitary 2021;24:878–86.ArticlePubMedPDF
• 33. Zhang F, He Q, Luo G, Long Y, Li R, Ding L, et al. The combination of 13N-ammonia and 11C-methionine in differentiation of residual/recurrent pituitary adenoma from the pituitary gland remnant after trans-sphenoidal Adenomectomy. BMC Cancer 2021;21:837.ArticlePubMedPMCPDF
• 34. Ishida A, Kaneko K, Minamimoto R, Hotta M, Inoshita N, Takano K, et al. Clinical decision-making based on 11Cmethionine PET in recurrent Cushing’s disease with equivocal MRI findings. J Neurosurg 2023;139:1671–80.ArticlePubMed
• 35. Pruis IJ, Verburg FA, Balvers RK, Harteveld AA, Feelders RA, Vernooij MW, et al. [18F]FET PET/MRI: an accurate technique for detection of small functional pituitary tumors. J Nucl Med 2024;65:688–92.ArticlePubMed
• 36. Furnica RM, Devuyst F, Mathey C, Constantinescu SM, De Herdt C, Alexopoulou O, et al. Diagnostic value of 11C-methionine PET-CT imaging in persistent or recurrent Cushing disease after surgery. J Clin Endocrinol Metab 2025;110:2845–52.ArticlePubMedPDF
• 37. Flaus A, Levigoureux E, Haesebaert J, Briet C, Castinetti F, Cristante J, et al. Prospective multicenter evaluation of [11C]methionine PET/MRI sensitivity compared with MRI for localizing small pituitary neuroendocrine tumor or pituitary adenoma in Cushing disease. J Nucl Med 2025;66:1575–80.ArticlePubMedPMC
• 38. Barbieri F, Thellung S, Wurth R, Gatto F, Corsaro A, Villa V, et al. Emerging targets in pituitary adenomas: role of the CXCL12/CXCR4-R7 system. Int J Endocrinol 2014;2014:753524.ArticlePubMedPMCPDF
• 39. Barbieri F, Bajetto A, Stumm R, Pattarozzi A, Porcile C, Zona G, et al. Overexpression of stromal cell-derived factor 1 and its receptor CXCR4 induces autocrine/paracrine cell proliferation in human pituitary adenomas. Clin Cancer Res 2008;14:5022–32.ArticlePubMedPDF
• 40. Ding J, Tong A, Hacker M, Feng M, Huo L, Li X. Usefulness of 68 Ga-Pentixafor PET/CT on diagnosis and management of Cushing syndrome. Clin Nucl Med 2022;47:669–76.ArticlePubMed
• 41. Wu Y, Wu Y, Yao B, Ren S, Wu S, Rui W, et al. Diagnostic accuracy and value of CXCR4-targeted PET/MRI using 68Ga-Pentixafor for tumor localization in Cushing disease. Radiology 2024;313:e233469.ArticlePubMed
• 42. Shukla J, Vatsa R, Walia R, Chhabra A, Rana N, Singh H, et al. Development of 68Ga DOTA-CRH for PET/CT imaging of ACTH-dependent Cushing’s disease: initial study. Cancer Biother Radiopharm 2021;36:642–50.ArticlePubMedPDF
• 43. Walia R, Gupta R, Bhansali A, Pivonello R, Kumar R, Singh H, et al. Molecular imaging targeting corticotropin-releasing hormone receptor for corticotropinoma: a changing paradigm. J Clin Endocrinol Metab 2021;106:e1816–26.ArticlePubMedPDF
• 44. Walia R, Chakraborty AM, Pandey S, Rana N, Kumar R, Ahuja C, et al. A novel molecular imaging technique using [68Ga]Ga-mDesmo PET-CT for localizing tumors in Cushing’s disease. Eur J Nucl Med Mol Imaging 2025;52:4558–68.ArticlePubMedPDF
• 45. Kim K, Kim D, Lee MH, Park YW, Ahn SS, Moon JH, et al. 68Ga-DOTATOC PET/CT in the localization of pituitary tumors in Cushing’s disease. Endocrinol Metab (Seoul) 2025;40:637–47.ArticlePubMedPMCPDF
• 46. Cassarino MF, Sesta A, Pagliardini L, Losa M, Lasio G, Cavagnini F, et al. Proopiomelanocortin, glucocorticoid, and CRH receptor expression in human ACTH-secreting pituitary adenomas. Endocrine 2017;55:853–60.ArticlePubMedPMCPDF
• 47. Dieterich KD, Gundelfinger ED, Ludecke DK, Lehnert H. Mutation and expression analysis of corticotropin-releasing factor 1 receptor in adrenocorticotropin-secreting pituitary adenomas. J Clin Endocrinol Metab 1998;83:3327–31.ArticlePubMed
• 48. de Keyzer Y, Rene P, Beldjord C, Lenne F, Bertagna X. Overexpression of vasopressin (V3) and corticotrophin-releasing hormone receptor genes in corticotroph tumours. Clin Endocrinol (Oxf) 1998;49:475–82.ArticlePubMedPDF
• 49. Luque RM, Ibanez-Costa A, Lopez-Sanchez LM, Jimenez-Reina L, Venegas-Moreno E, Galvez MA, et al. A cellular and molecular basis for the selective desmopressin-induced ACTH release in Cushing disease patients: key role of AVPR1b receptor and potential therapeutic implications. J Clin Endocrinol Metab 2013;98:4160–9.ArticlePubMed
• 50. Pandey S, Walia R, Kaur G, Pandav K, Rather I, Rana N, et al. Using the PET/CT radiotracer [68Ga]Ga-DOTA-mDesmo to target V1b receptors and localize corticotropinoma in Cushing’s disease. Commun Med (Lond) 2025;5:367.ArticlePubMedPMCPDF

Figure & Data

References

Citations

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