Biodistribution and Radiation Dosimetry for 68Ga-DOTA-CCK-66, a Novel CCK2R-Targeting Compound for Imaging of Medullary Thyroid Cancer.
Journal
Clinical nuclear medicine
ISSN: 1536-0229
Titre abrégé: Clin Nucl Med
Pays: United States
ID NLM: 7611109
Informations de publication
Date de publication:
02 Aug 2024
02 Aug 2024
Historique:
medline:
2
8
2024
pubmed:
2
8
2024
entrez:
2
8
2024
Statut:
aheadofprint
Résumé
Cholecystokinin 2 receptor (CCK2R) is a promising target for imaging and treatment of medullary thyroid cancer due to its overexpression in over 90% of tumor cells. 68Ga-DOTA-CCK-66 is a recently introduced PET tracer selective for CCK2R, which has shown favorable pharmacokinetics in vivo in preclinical experiments. In order to further investigate safety and suitability of this tracer in the human setting, whole-body distribution and radiation dosimetry were evaluated. Six patients with a history of medullary thyroid cancer were injected intravenously with 169 ± 19 MBq of 68Ga-DOTA-CCK-66. Whole-body PET/CT scans were acquired at 10 minutes, 1 hour, 2 hours, and 4 hours after tracer injection. Time-activity curves per organ were determined, and mean organ-absorbed doses and effective doses were calculated using OLINDA/EXM. Injection of a standard activity of 150 MBq of 68Ga-DOTA-CCK-66 results in an effective dose of 4.5 ± 0.9 mSv. The highest absorbed organ doses were observed in the urinary bladder wall (40 mGy) and the stomach (15 mGy), followed by the kidneys (6 mGy), as well as the liver and the spleen (3 mGy each). CCK2R-expressing tumor manifestations could be detected in 2 of the 6 patients, including lymph node, bone, and liver metastases. 68Ga-DOTA-CCK-66 exhibits a favorable dosimetry. Beyond physiologic receptor expression of the stomach, no other relevant tracer accumulation could be observed, rendering this organ at risk in case of subsequent radioligand therapy using 177Lu-DOTA-CCK-66.
Identifiants
pubmed: 39093043
doi: 10.1097/RLU.0000000000005355
pii: 00003072-990000000-01238
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.
Déclaration de conflit d'intérêts
Conflicts of interest and sources of funding: A patent application on CCK2R-targeted compounds including DOTA-CCK-66 with T.G., N.H., C.L., and H.J.W. as inventors has been filed. H.J.W. is founder and shareholder of Scintomics GmbH, Munich, Germany. No other potential conflicts of interest relevant to this article exist. This study has been funded by Deutsche Forschungsgemeinschaft (DFG, German Research Foundation—461577150).
Références
Wells SA Jr., Asa SL, Dralle H, et al. American Thyroid Association guidelines task force on medullary thyroid carcinoma. Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. Thyroid. 2015;25:567–610.
Wells SA Jr., Robinson BG, Gagel RF, et al. Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial. J Clin Oncol. 2012;30:134–141.
Hadoux J, Elisei R, Brose MS, et al. Phase 3 trial of selpercatinib in advanced RET-mutant medullary thyroid cancer. N Engl J Med. 2023;389:1851–1861.
Hadoux J, Schlumberger M. Chemotherapy and tyrosine-kinase inhibitors for medullary thyroid cancer. Best Pract Res Clin Endocrinol Metab. 2017;31:335–347.
Vodopivec DM, Hu MI. RET kinase inhibitors for RET-altered thyroid cancers. Ther Adv Med Oncol. 2022;14:17588359221101691.
Terroir M, Caramella C, Borget I, et al. F-18-Dopa positron emission tomography/computed tomography is more sensitive than whole-body magnetic resonance imaging for the localization of persistent/recurrent disease of medullary thyroid cancer patients. Thyroid. 2019;29:1457–1464.
Giraudet AL, Vanel D, Leboulleux S, et al. Imaging medullary thyroid carcinoma with persistent elevated calcitonin levels. J Clin Endocrinol Metab. 2007;92:4185–4190.
Giovanella L, Treglia G, Iakovou I, et al. EANM practice guideline for PET/CT imaging in medullary thyroid carcinoma. Eur J Nucl Med Mol Imaging. 2020;47:61–77.
Romero-Lluch AR, Cuenca-Cuenca JI, Guerrero-Vázquez R, et al. Diagnostic utility of PET/CT with 18F-DOPA and 18F-FDG in persistent or recurrent medullary thyroid carcinoma: the importance of calcitonin and carcinoembryonic antigen cutoff. Eur J Nucl Med Mol Imaging. 2017;44:2004–2013.
Reubi JC, Schaer JC, Waser B. Cholecystokinin(CCK)-a and CCK-B/gastrin receptors in human tumors. Cancer Res. 1997;57:1377–1386.
Behr TM, Béhé MP. Cholecystokinin-B/gastrin receptor-targeting peptides for staging and therapy of medullary thyroid cancer and other cholecystokinin-B receptor-expressing malignancies. Semin Nucl Med. 2002;32:97–109.
Lezaic L, Erba PA, Decristoforo C, et al. [111In]in-CP04 as a novel cholecystokinin-2 receptor ligand with theranostic potential in patients with progressive or metastatic medullary thyroid cancer: final results of a GRAN-T-MTC phase I clinical trial. Eur J Nucl Med Mol Imaging. 2023;50:892–907.
Grossrubatscher E, Fanciulli G, Pes L, et al. Advances in the management of medullary thyroid carcinoma: focus on peptide receptor radionuclide therapy. J Clin Med. 2020;9:3507.
Rottenburger C, Nicolas GP, McDougall L, et al. Cholecystokinin 2 receptor agonist 177Lu-PP-F11N for radionuclide therapy of medullary thyroid carcinoma: results of the Lumed phase 0a study. J Nucl Med. 2020;61:520–526.
von Guggenberg E, Uprimny C, Klinger M, et al. Preliminary clinical experience with cholecystokinin-2 receptor PET/CT using the 68Ga-labeled minigastrin analog DOTA-MGS5 in patients with medullary thyroid cancer. J Nucl Med. 2023;64:859–862.
Günther T, Holzleitner N, Viering O, et al. Preclinical evaluation of minigastrin analogs and proof-of-concept [68Ga]Ga-DOTA-CCK-66 PET/CT in 2 patients with medullary thyroid cancer. J Nucl Med. 2024;65:33–39.
Viering O, Günther T, Holzleitner N, et al. CCK2 receptor-targeted PET/CT in medullary thyroid cancer using [68Ga]Ga-DOTA-CCK-66. J Nucl Med. 2024;65:493–494.
Huizing DMV, Koopman D, van Dalen JA, et al. Multicentre quantitative 68Ga PET/CT performance harmonisation. EJNMMI Phys. 2019;6:19.
Herrmann K, Lapa C, Wester HJ, et al. Biodistribution and radiation dosimetry for the chemokine receptor CXCR4-targeting probe 68Ga-pentixafor. J Nucl Med. 2015;56:410–416.
Kletting P, Schimmel S, Kestler HA, et al. Molecular radiotherapy: the NUKFIT software for calculating the time-integrated activity coefficient. Med Phys. 2013;40:102504.
Stabin MG, Sparks RB, Crowe E. OLINDA/EXM: the second-generation personal computer software for internal dose assessment in nuclear medicine. J Nucl Med. 2005;46:1023–1027.
Ferrer L, Kraeber-Bodéré F, Bodet-Milin C, et al. Three methods assessing red marrow dosimetry in lymphoma patients treated with radioimmunotherapy. Cancer. 2010;116(4 Suppl):1093–1100.
The 2007 Recommendations of the International Commission on Radiological Protection. ICRP publication 103. Ann ICRP. 2007;37(2–4):1–332.
1990 Recommendations of the International Commission on Radiological Protection. Ann ICRP. 1991;21(1–3):1–201.
Herrmann K, Bluemel C, Weineisen M, et al. Biodistribution and radiation dosimetry for a probe targeting prostate-specific membrane antigen for imaging and therapy. J Nucl Med. 2015;56:855–861.
ICRP. Radiation dose to patients from radiopharmaceuticals. Addendum 3 to ICRP Publication 53. ICRP Publication 106. Approved by the Commission in October 2007. Ann ICRP. 2008;38(1–2):1–197.
Sandström M, Velikyan I, Garske-Román U, et al. Comparative biodistribution and radiation dosimetry of 68Ga-DOTATOC and 68Ga-DOTATATE in patients with neuroendocrine tumors. J Nucl Med. 2013;54:1755–1759.
Sartor O, de Bono J, Chi KN, et al. VISION investigators. Lutetium-177-PSMA-617 for metastatic castration-resistant prostate cancer. N Engl J Med. 2021;385:1091–1103.
Pavel M, Öberg K, Falconi M, et al. ESMO guidelines committee. Gastroenteropancreatic neuroendocrine neoplasms: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2020;31:844–860.
Barrett TD, Lagaud G, Wagaman P, et al. The cholecystokinin CCK2 receptor antagonist, JNJ-26070109, inhibits gastric acid secretion and prevents omeprazole-induced acid rebound in the rat. Br J Pharmacol. 2012;166:1684–1693.
Emami B, Lyman J, Brown A, et al. Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys. 1991;21:109–122.
Rottenburger C, Nicolas G, McDougall L, et al. The CCK-2 receptor agonist Lu-177-PP-F11N for PRRT of medullary thyroid cancer—recent results of the phase 1 “LUMED” study. Nuklearmedizin. 2021;60:L15.