Adrenal Bez Kitlelerini Değerlendirmede Nükleer Tıp Yöntemleri
Özet
Adrenal bez kitlelerinin değerlendirilmesinde nükleer tıp yöntemlerinin ve radyofarmasötiklerin rolünü inceleyen bu çalışmada, BT ve MRG gibi morfolojik görüntüleme tekniklerinin yaygınlaşmasıyla rastlantısal adrenal kitle saptanma oranının yaklaşık %5'e yükseldiği belirtilmektedir. Bu kitlelerin iyi huylu veya kötü huylu ayrımı ile hormonal aktivitelerinin belirlenmesinde, enzim ve reseptörleri hedef alan nükleer-moleküler fonksiyonel görüntüleme (SPECT/BT ve PET/BT) yöntemleri kritik öneme sahiptir. Fonksiyonel nükleer tıp mekanizmaları; adrenal korteks ve medulla görüntüleme, artmış glukoz metabolizması ve artmış reseptör ekspresyonu olmak üzere dört ana başlık altında ele alınmaktadır. Korteks lezyonlarında NP-59 gibi kolesterol analogları ve 11C-MTO gibi PET ajanları tercih edilirken; medulladan köken alan feokrositoma ve nöroblastom gibi lezyonların tanı ve takibinde MIBG sintigrafisi ile 18F-DOPA/DPA gibi gelişmiş PET radyoizotoplarından yararlanılmaktadır. Ayrıca, onkolojik rutinlerde sıklıkla kullanılan 18F-FDG PET/BT yüksek metabolik aktiviteyi göstererek malignite ayrımına katkı sağlarken, somatostatin reseptör hedefli 68Ga-DOTA peptidleri ve CXCR4'ü hedefleyen 68Ga-Pentixafor gibi yeni ajanlar teranostik potansiyelleriyle öne çıkmaktadır.
The nuclear medicine methods and radiopharmaceuticals utilized in evaluating adrenal gland masses are thoroughly examined in this study, which highlights that the detection rate of incidental adrenal masses has increased to approximately 5% due to the widespread use of morphological imaging techniques like CT and MRI. Nuclear-molecular functional imaging methods (SPECT/CT and PET/CT), targeting enzymes and receptors, are of critical importance in differentiating between benign and malignant masses and determining their hormonal activity. The functional nuclear medicine mechanisms are discussed under four main headings: adrenal cortex and medulla imaging, increased glucose metabolism, and increased receptor expression. For cortical lesions, cholesterol analogs like NP-59 and PET agents like 11C-MTO are preferred; whereas MIBG scintigraphy and advanced PET radioisotopes such as 18F-DOPA/DPA are used for the diagnosis and follow-up of medulla-originating lesions like pheochromocytoma and neuroblastoma. Furthermore, 18F-FDG PET/CT, frequently used in oncological routines, contributes to malignancy differentiation by demonstrating high metabolic activity, while novel agents targeting somatostatin receptors like 68Ga-DOTA peptides and CXCR4-targeting 68Ga-Pentixafor stand out for their theranostic potential.
Referanslar
Song JH, Chaudhry FS, Mayo-Smith WW. The incidental adrenal mass on CT: prevalence of adrenal disease in 1,049 consecutive adrenal masses in patients with no known malignancy. American journal of roentgenology. 2008 May;190(5):1163-8. doi: 10.2214/AJR.07.2799. PMID: 18430826.
Gust L, Taieb D, Beliard A, et al. Preoperative 18FFDG uptake is strongly correlated with malignancy, Weiss score, and molecular markers of aggressiveness in adrenal cortical tumors. World journal of surgery. 2012;36 (6): 1406–10.
Hahner S, Kreissl MC, Fassnacht M, et al. [131I] iodometomidate for targeted radionuclide therapy of advanced adrenocortical carcinoma. The Journal of Clinical Endocrinology & Metabolism. 2012;97(3): 914–22.
Yalniz C, Morani AC, Waguespack SG, et al. Imaging of adrenalrelated endocrine disorders. Radiologic clinics of North America. 2020; 58: 1099–1113.
Barzon L, Sonino N, Fallo F, et al. Prevalence and natural history of adrenal incidentalomas. European journal of endocrinology. 2003;149(4): 273–85.
Wang T, Satoh F, Morimoto R, et al. Gene expression profiles in aldosterone-producing adenomas and adjacent adrenal glands. European journal of endocrinology. 2011;164(4): 613–9.
NIH state-of-the-science statement on management of the clinically inapparent adrenal mass ("incidentaloma"). NIH consensus and state-of-the-science statements. 2002;19(2): 1– 25.
Kloos RT, Gross MD, Francis IR, et al. Incidentally discovered adrenal masses. Endocrine reviews. 1995;16: 460–84.
Aron DC. The adrenal incidentaloma: disease of modern technology and public health problem. Reviews in endocrine & metabolic disorders. 2001;2: 335–42.
Bovio S, Cataldi A, Reimondo G, et al. Prevalence of adrenal incidentaloma in a contemporary computerized tomography series. Journal of endocrinological investigation. 2006;29: 298–302.
Kebebew E. Adrenal incidentaloma. The New England journal of medicine. 2021;384(16): 1542–51.
Sherlock M, Scarsbrook A, Abbas A, et al. Adrenal Incidentaloma. Endocrine reviews. 2020;41(6): 775-820.
Fassnacht M, Arlt W, Bancos I, et al. Management of adrenal incidentalomas: european society of endocrinology clinical practice guideline in collaboration with the European network for the study of adrenal tumors. European journal of endocrinology. 2016;175(2): G1–G34.
Rubello D, Bui C, Casara D, et al. Functional scintigraphy of the adrenal gland. European journal of endocrinology. 2002;147(1): 13–28.
Wong KK, Fig LM, Youssef E, et al. Endocrine scintigraphy with hybrid SPECT/CT. Endocrine reviews. 2014;35: 717–746.
Yen RF, Wu VC, Liu KL, et al. 131I-6beta-iodomethyl-19-norcholesterol SPECT/CT for primary aldosteronism patients with inconclusive adrenal venous sampling and CT results. Journal of Nuclear Medicine. 2009;50 (10): 1631–7.
Mendichovszky IA, Powlson AS, Manavaki R, et al. Targeted Molecular Imaging in Adrenal Disease-An Emerging Role for Metomidate PET-CT. Diagnostics (Basel). 2016 Nov 18;6(4):42. doi: 10.3390/diagnostics6040042. PMID: 27869719; PMCID: PMC5192517.
Hahner S, Stuermer A, Kreissl M, et al. [123 I]Iodometomidate for molecular imaging of adrenocortical cytochrome P450 family 11B enzymes. The Journal of Clinical Endocrinology & Metabolism. 2008;93(6): 2358–65.
Hahner S, Kreissl MC, Fassnacht M, et al. Functional characterization of adrenal lesions using [123I]IMTO-SPECT/CT. The Journal of Clinical Endocrinology & Metabolism. 2013;98(4): 1508–18.
Werner RA, Schirbel A, Buck AK, et al. Adrenal functional imaging. Presse Medicale. 2022 Feb 4;51(2): 104114. doi: 10.1016/j.lpm.2022.104114. Epub ahead of print. PMID: 35131316.
Jonson SD, Welch MJ. Synthesis, biological evaluation, and baboon PET imaging of the potential adrenal imaging agent cholesteryl-p-[18F]fluorobenzoate. Nuclear Medicine and Biology. 1999 Jan;26(1): 131-8. doi: 10.1016/s0969-8051(98)00081-x. PMID: 10096513.
Weber MM, Lang J, Abedinpour F, et al. Different inhibitory effect of etomidate and ketoconazole on the human adrenal steroid biosynthesis. The Clinical investigator. 1993;71(11): 933–8.
Fassnacht M, Hahner S, Beuschlein F, et al. New mechanisms of adrenostatic compounds in a human adrenocortical cancer cell line. European journal of clinical investigation. 2000;30(Suppl 3): 76–82.
Bergstrom M, Bonasera TA, Lu L, et al. In vitro and in vivo primate evaluation of carbon-11-etomidate and carbon-11-metomidate as potential tracers for PET imaging of the adrenal cortex and its tumors. Journal of Nuclear Medicine. 1998;39(6): 982–9.
Bergstrom M, Juhlin C, Bonasera TA, et al. PET imaging of adrenal cortical tumors with the 11beta-hydroxylase tracer 11Cmetomidate. Journal of Nuclear Medicine. 2000;41(2): 275–82.
O’Shea PM, O’Donoghue D, Bashari W, et al. (11) C-Metomidate PET/CT is a useful adjunct for lateralization of primary aldosteronism in routine clinical practice. Clinical endocrinology. 2019; 90: 670–679.
Hennings J, Lindhe O, Bergstrom M, et al. [11C] metomidate positron emission tomography of adrenocortical tumors in correlation with histopathological findings. The Journal of Clinical Endocrinology & Metabolism. 2006;91(4): 1410–4.
Burton TJ, Mackenzie IS, Balan K, et al. Evaluation of the sensitivity and specificity of (11)C-metomidate positron emission tomography (PET)-CT for lateralizing aldosterone secretion by Conn's adenomas. The Journal of Clinical Endocrinology & Metabolism. 2012;97(1): 100–9.
Soinio M, Luukkonen AK, Seppänen M, et al. Functional imaging with 11C-metomidate PET for subtype diagnosis in primary aldosteronism. European journal of endocrinology. 2020 Dec;183(6): 539-550. doi: 10.1530/EJE-20-0532. PMID: 33055298; PMCID: PMC8045447.
Hennings J, Hellman P, Ahlstrom H, et al. Computed tomography, magnetic resonance imaging and 11C-metomidate positron emission tomography for evaluation of adrenal incidentalomas. European journal of radiology. 2009;69: 314–23.
Minn H, Salonen A, Friberg J, et al. Imaging of adrenal incidentalomas with PET using (11)C-metomidate and (18)F-FDG. Journal of Nuclear Medicine. 2004;45: 972–9.
Khan TS, Sundin A, Juhlin C, et al. 11Cmetomidate PET imaging of adrenocortical cancer. European journal of nuclear medicine and molecular imaging. 2003;30: 403–10.
Bongarzone S, Basagni F, Sementa T, et al. Development of [(18)F]FAMTO: a novel fluorine-18 labelled positron emission tomography (PET) radiotracer for imaging CYP11B1 and CYP11B2 enzymes in adrenal glands. Nuclear medicine and biology. 2019;68–69: 14–21.
Abe T, Naruse M, Young WF, et al. A Novel CYP11B2- specific imaging agent for detection of unilateral subtypes of primary aldosteronism. The Journal of Clinical Endocrinology & Metabolism. 2016;101(3): 1008–15.
Ding J, Zhang Y, Wen J, et al. Imaging CXCR4 expression in patients with suspected primary hyperaldosteronism. European journal of nuclear medicine and molecular imaging. 2020;47(11): 2656–65.
Wadsak W, Mitterhauser M, Rendl G, et al. [18F] FETO for adrenocortical PET imaging: a pilot study in healthy volunteers. European journal of nuclear medicine and molecular imaging. 2006;33(6): 669–72.
Silins I, Sundin A, Nordeman P, et al. Parachloro-2-[(18)F]fluoroethyl-etomidate: a promising new PET radiotracer for adrenocortical imaging. International journal of medical sciences. 2021;18(10):2187–96
GrossMD, AvramA, Fig LM, et al. PET inthediagnostic evaluation of adrenal tumors. The quarterly journal of nuclear medicine and molecular imaging. 2007;51: 272–83.
Gross MD, Avram A, Fig LM, et al. Contemporary adrenal scintigraphy. European journal of nuclear medicine and molecular imaging. 2007;34: 547–57.
Ilias I, Pacak K. A clinical overview of pheochromocytomas/paragangliomas and carcinoid tumors. Nuclear medicine and biology. 2008;35(Suppl 1): S27–34.
Sundin A, Hindié E, Avram AM, et al. A Clinical Challenge: Endocrine and Imaging Investigations of Adrenal Masses. Journal of nuclear medicine. 2021 Jul;62(Suppl 2): 26S-33S. doi: 10.2967/jnumed.120.246066. PMID: 34230070.).
Rufini V, Treglia G, Perotti G, et al. The evolution in the use of MIBG scintigraphy in pheochromocytomas and paragangliomas. Hormones (Athens). 2013;12: 58-68.
Wiseman GA, Pacak K, O'Dorisio MS, et al. Usefulness of 123I-MIBG scintigraphy in the evaluation of patients with known or suspected primary or metastatic pheochromocytoma or paraganglioma: results from a prospective multicenter trial. Journal of Nuclear Medicine. 2009;50(9): 1448–54.
de Kraker J, Hoefnagel KA, Verschuur AC, et al. Iodine-131-metaiodobenzylguanidine as initial induction therapy in stage 4 neuroblastoma patients over 1 year of age. European journal of cancer. 2008;44: 551-556.
Shulkin BL, Wieland DM, Schwaiger M, et al. PET scanning with hydroxyephedrine: an approach to the localization of pheochromocytoma. Journal of Nuclear Medicine. 1992;33(6): 1125–31.
Minn H, Kauhanen S, Seppanen M, et al. 18F-FDOPA: a multiple-target molecule. Journal of Nuclear Medicine. 2009;50: 1915–8.
Ilias I, Yu J, Carrasquillo JA, et al. Superiority of 6-[18F]-fluorodopamine positron emission tomography versus [131I]-metaiodobenzylguanidine scintigraphy in the localization of metastatic pheochromocytoma. The Journal of Clinical Endocrinology & Metabolism. 2003;88: 4083–7.
Timmers HJ, Eisenhofer G, Carrasquillo JA, et al. Use of 6-[18F]-fluorodopamine positron emission tomography (PET) as first-line investigation for the diagnosis and localization of non-metastatic and metastatic phaeochromocytoma (PHEO). Clinical Endocrinology. 2009;71: 11–7.
Kaji P, Carrasquillo JA, Linehan WM, et al. The role of 6-[18F] fluorodopamine positron emission tomography in the localization of adrenal pheochromocytoma associated with von Hippel–Lindau syndrome. European journal of endocrinology. 2007;156: 483–7.
Hoegerle S, Altehoefer C, Ghanem N, et al. 18F-DOPA positron emission tomography for tumour detection in patients with medullary thyroid carcinoma and elevated calcitonin levels. European journal of nuclear medicine. 2001;28(1): 64– 71.
Timmers HJ, Chen CC, Carrasquillo JA, et al. Comparison of 18F-fluoro-LDOPA, 18F-fluoro-deoxyglucose, and 18F-fluorodopamine PET and 123I-MIBG scintigraphy in the localization of pheochromocytoma and paraganglioma. The Journal of Clinical Endocrinology & Metabolism. 2009;94: 4757–67.
Timmers HJ, Kozupa A, Chen CC, et al. Superiority of fluorodeoxyglucose positron emission tomography to other functional imaging techniques in the evaluation of metastatic SDHB-associated pheochromocytoma and paraganglioma. Journal of clinical oncology. 2007;25: 2262–9.
Bagheri B, Maurer AH, Cone L, et al. Characterization of the normal adrenal gland with 18F-FDG PET/CT. Journal of Nuclear Medicine. 2004;45: 1340–3.
Wong KK, Arabi M, Bou-Assaly W, et al. Evaluation of incidentally discovered adrenal masses with PET and PET/CT. European journal of radiology. 2012 Mar;81(3):441-50. doi: 10.1016/j.ejrad.2010.12.060. Epub 2011 Feb 4. PMID: 21295930.
Yun M, Kim W, Alnafisi N, et al. 18F-FDG PET in characterizing adrenal lesions detected on CT or MRI. Journal of Nuclear Medicine. 2001;42: 1795–1799.
Kumar R, Xiu Y, Yu JQ, et al. 18F-FDG PET in evaluation of adrenal lesions in patients with lung cancer. Journal of Nuclear Medicine. 2004; 45: 2058–2062.
Jagtiani M, Boland GWL, Blake MA, et al. (2008) Characerization of adrenal lesions using 18F-FDG PET: an analysis of hte PET literature. Presented at the 94th Scientific Assembly and Annual Meeting, Radiological Society of North America, Chicago, IL, 30 Nov–5 Dec
Boland GWL, Blake MA, Holalkere NS, et al. PET/CT for the characterization of adrenal masses in patients with cancer: qualitative versus quantitative accuracy in 150 consecutive patients. American journal of roentgenology. 2009;192: 956–962
Boland GW, Dwamena BA, Jagtiani Sangwaiya M, et al. Characterization of adrenal masses by using FDG PET: a systematic review and meta-analysis of diagnostic test performance. Radiology. 2011;259(1): 117– 26.
Salgues B, Guerin C, Amodru V, et al. Risk stratification of adrenal masses by [(18) F]FDG PET/CT: changing tactics. Clinical endocrinology. 2021;94: 133–140.
Dinnes J, Bancos I, Ferrante di Ruffano L, et al. Management of endocrine disease: imaging for the diagnosis of malignancy in incidentally discovered adrenal masses: a systematic review and meta-analysis. European journal of endocrinology. 2016;175(2): R51–64.
Ishiwata K, Suzuki S, Igarashi K, et al. Characteristics of benign adrenocortical adenomas with 18F-FDG PET accumulation. European journal of endocrinology. 2021;185(1): 155–65.
Vikram R, Yeung HD, Macapinlac HA, et al. Utility of PET/CT in differentiating benign from malignant adrenal nodules in patients with cancer. American journal of roentgenology. 2008;191: 1545–51.
Ansquer C, Scigliano S, Mirallie E, et al. (18)F-FDG PET/CT in the characterization and surgical decision concerning adrenal masses a prospective multicentre evaluation. European journal of nuclear medicine and molecular imaging. 2010;37(9): 1669-1678.
Gratz S, Kemke B, Kaiser W, et al. Incidental nonsecreting adrenal masses in cancer patients: intra-individual comparison of 18F-fluorodeoxyglucose positron emission tomography/computed tomography with computed tomography and shift magnetic resonance imaging. The Journal of international medical research. 2010;38: 633–44.
Groussin L, Bonardel G, Silvera S, et al. 18F-Fluorodeoxyglucose positron emission tomography for the diagnosis of adrenocortical tumors: a prospective study in 77 operated patients. The Journal of Clinical Endocrinology & Metabolism. 2009;94(5): 1713–22.
Leboulleux S, Dromain C, Bonniaud G, et al. Diagnostic and prognostic value of 18-fluorodeoxyglucose positron emission tomography in adrenocortical carcinoma: a prospective comparison with computed tomography. The Journal of Clinical Endocrinology & Metabolism. 2006;91(3): 920–5.
Mackie GC, Shulkin BL, Ribeiro RC, et al. Use of [18F]fluorodeoxyglucose positron emission tomography in evaluating locally recurrent and metastatic adrenocortical carcinoma. The Journal of Clinical Endocrinology & Metabolism. 2006;91(7): 2665–71.
Becherer A, Vierhapper H, Potzi C, et al. FDG-PET in adrenocortical carcinoma. Cancer biotherapy & radiopharmaceuticals. 2001;16: 289–95.
Tenenbaum F, Groussin L, Foehrenbach H, et al. 18F-fluorodeoxyglucose positron emission tomography as a diagnostic tool for malignancy of adrenocortical tumours? Preliminary results in 13 consecutive patients. European journal of endocrinology. 2004;150: 789–92.
Shulkin BL, Koeppe RA, Francis IR, et al. Pheochromocytomas that do not accumulate metaiodobenzylguanidine: Localization with PET and administration of FDG. Radiology. 1993;186: 711-5.
Blake MA, Kalra MK, Maher MM, et al. Pheochromocytoma: an imaging chameleon. Radiographics. 2004;24: S87–S89
Blake MA, Krisnamoorthy SK, Boland GW, et al. Low density pheochromocytoma on CT: a mimicker of adrenal adenoma. American journal of roentgenology. 2003;181: 1663–1668
Chong S, Lee KS, Kim HY, et al. Integrated PET CT for the characterization of adrenal gland lesions in cancer patients: Diagnostic Efficacy and interpretation pitfalls. Radiographics. 2006;26: 1811-24.
Shulkin BL, Thompson NW, Shapiro B, et al. Pheochromocytomas: imaging with 2-[fluorine-18]fluoro-2-deoxy-d-glucose PET. Radiology. 1999;212: 35–41.
Taieb D, Sebag F, Barlier A, et al. 18F-FDG avidity of pheochromocytomas and paragangliomas: a new molecular imaging signature? Journal of Nuclear Medicine. 2009;50: 711–7.
Fottner C, Helisch A, Anlauf M, et al. 6-18F-fluoro-l-dihydroxyphenylalanine positron emission tomography is superior to 123I-metaiodobenzyl-guanidine scintigraphy in the detection of extraadrenal and hereditary pheochromocytomas and paragangliomas: correlation with vesicular monoamine transporter expression. The Journal of Clinical Endocrinology & Metabolism. 2010;95: 2800–10.
Balon HR, Brown TL, Goldsmith SJ, et al. The SNM practice guideline for somatostatin receptor scintigraphy 2.0. Journal of Nuclear Medicine. Technol. 2011;39: 317–24.
Kaltsas G, Korbonits M, Heintz E, et al. Comparison of somatostatin analog and meta-iodobenzylguanidine radionuclides in the diagnosis and localization of advanced neuroendocrine tumors. The Journal of Clinical Endocrinology & Metabolism. 2001;86(2): 895–902.
Pettinato C, Sarnelli A, Di Donna M, et al. 68Ga-DOTANOC: biodistribution and dosimetry in patients affected by neuroendocrine tumours. European journal of nuclear medicine and molecular imaging. 2008;35: 72–9.
Buchmann I, Henze M, Engelbrecht S, et al. Comparison of 68Ga-DOTATOC PET and 111In-DTPAOC (Octreoscan) SPECT in patients with neuroendocrine tumours. European journal of nuclear medicine and molecular imaging. 2007;34: 1617–26.
Koukouraki S, Strauss LG, Georgoulias V, et al. Comparison of the pharmacokinetics of 68GaDOTATOC and [18F]FDG in patients with metastatic neuroendocrine tumours scheduled for 90Y-DOTATOC therapy. European journal of nuclear medicine and molecular imaging. 2006;33: 1115–22.
Sharma P, Mukherjee A, Karunanithi S, et al. Accuracy of 68Ga DOTANOC PET/CT Imaging in Patients With Multiple Endocrine Neoplasia Syndromes. Clinical nuclear medicine. 2015;40: e351–6.
Chang CA, Pattison DA, Tothill RW, et al. (68)Ga-DOTATATE and (18)F-FDG PET/CT in Paraganglioma and Pheochromocytoma: utility, patterns and heterogeneity. Cancer Imaging. 2016;16(1): 1-12.
Han S, Suh CH, Woo S, et al. Performance of (68)GaDOTA-Conjugated Somatostatin Receptor Targeting Peptide PET in Detection of Pheochromocytoma and Paraganglioma: A Systematic Review and Meta-Analysis. Journal of nuclear medicine. 2019;60: 369–76.
Domanska UM, Kruizinga RC, Nagengast WB, et al. A review on CXCR4/CXCL12 axis in oncology: no place to hide. European journal of cancer. 2013;49(1): 219–30.
Werner RA, Kircher S, Higuchi T, et al. CXCR4- directed imaging in solid tumors. Frontiers in oncology. 2019;9: 770.
Bluemel C, Hahner S, Heinze B, et al. Investigating the chemokine receptor 4 as potential theranostic target in adrenocortical cancer patients. Clinical nuclear medicine. 2017;42(1): e 29–34.
Heinze B, Fuss CT, Mulatero P, et al. Targeting CXCR4 (CXC Chemokine Receptor Type 4) for molecular imaging of aldosteroneproducing adenoma. Hypertension. 2018;71(2): 317–25
Ding J, Tong A, Zhang Y, et al. Functional characterization of adrenocortical masses in nononcological patients using [(68)Ga]-pentixafor. Journal of Nuclear Medicine. 2022; 63: 368–375.
Gu Y, Gu W, Dou J, et al. Diagnostic role of prostate-specific membrane antigen in adrenocortical carcinoma. Frontiers in endocrinology. 2019;10: 226. (Lausanne).
