Neuroendocrinology
Rapid Communication
Non-Invasive Imaging Methodologies for Assessment of Radiation Damage to Bone Marrow and Kidneys from Peptide Receptor Radionuclide TherapyAhlstedt J.a · Johansson E.b · Sydoff M.c · Karlsson H.a · Thordarson E.a · Gram M.a · Eriksson O.b,daA1M Pharma AB, Lund, Sweden
bAntaros Medical AB, Mölndal, Sweden cLund University Bioimaging Center, Lund University, Lund, Sweden dScience for Life Laboratory, Department of Medicinal Chemistry, Uppsala, Sweden |
|
Log in to MyKarger to check if you already have access to this content.
KAB
Buy a Karger Article Bundle (KAB) and profit from a discount!
If you would like to redeem your KAB credit, please log in.
Save over 20% compared to the individual article price.
Article / Publication Details
Received: December 31, 2018
Accepted: April 17, 2019
Published online: April 19, 2019
Issue release date: January 2020
Number of Print Pages: 9
Number of Figures: 4
Number of Tables: 0
ISSN: 0028-3835 (Print)
eISSN: 1423-0194 (Online)
For additional information: https://www.karger.com/NEN
Abstract
Background/Aims: Peptide receptor radionuclide therapy (PRRT) is becoming clinical routine for management of neuroendocrine tumours. The number of PRRT cycles is correlated with treatment effect but theoretically limited by off-target radiation damage to kidneys and bone marrow. New imaging biomarkers for assessment of PRRT tissue damage would enable evaluation of novel renal and bone marrow protective agents, as well as personalised PRRT treatment regiments. Methods: Mice treated with [177Lu]Lu-DOTA-TATE PRRT or vehicle were examined at baseline and following treatment with [18F]fluorothymidine (FLT) positron emission tomography (PET) and technetium-99m-mercapto-acetyl-tri-glycine ([99mTc]Tc-Mag3) single-photon emission tomography (SPECT) to assess dynamic changes in bone marrow proliferation and renal function, respectively. Results: Bone marrow proliferation as assessed by [18F]FLT was decreased 2 days after PRRT treatment, but not vehicle, compared to baseline (target-to-background ratio [TBRmax] baseline:1.69 ± 0.29 vs. TBRmax PRRT: 0.91 ± 0.02, p < 0.01). Renal function as assessed by [99mTc]Tc-Mag3 SPECT was similarly decreased 2 days following PRRT compared to vehicle (fractional uptake rate [FUR] vehicle: 0.030 ± 0.014 s–1 vs. FUR PRRT: 0.0051 ± 0.0028 s–1, p < 0.01). Conclusion: [18F]FLT PET and [99mTc]Tc-Mag3 SPECT are promising techniques for assessing bone marrow and renal injury from [177Lu]Lu-DOTA-TATE PRRT and may potentially improve patient management by allowing evaluation of protective interventions as well as enabling personalised PRRT treatments.
© 2019 S. Karger AG, Basel
Related Articles:
References
- Otte A, Mueller-Brand J, Dellas S, Nitzsche EU, Herrmann R, Maecke HR. Yttrium-90-labelled somatostatin-analogue for cancer treatment. Lancet. 1998 Feb;351(9100):417–8.
- Kwekkeboom DJ, Teunissen JJ, Bakker WH, Kooij PP, de Herder WW, Feelders RA, et al. Radiolabeled somatostatin analog [177Lu-DOTA0,Tyr3]octreotate in patients with endocrine gastroenteropancreatic tumors. J Clin Oncol. 2005 Apr;23(12):2754–62.
- Strosberg J, El-Haddad G, Wolin E, Hendifar A, Yao J, Chasen B, et al.; NETTER-1 Trial Investigators. Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors. N Engl J Med. 2017 Jan;376(2):125–35.
- Hicks RJ, Kwekkeboom DJ, Krenning E, Bodei L, Grozinsky-Glasberg S, Arnold R, et al.; Antibes Consensus Conference participants. ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Neoplasia: Peptide Receptor Radionuclide Therapy with Radiolabeled Somatostatin Analogues. Neuroendocrinology. 2017;105(3):295–309.
- Emami B, Lyman J, Brown A, Coia L, Goitein M, Munzenrider JE, et al. Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys. 1991 May;21(1):109–22.
- Huizing DM, de Wit-van der Veen BJ, Verheij M, Stokkel MP. Dosimetry methods and clinical applications in peptide receptor radionuclide therapy for neuroendocrine tumours: a literature review. EJNMMI Res. 2018 Aug;8(1):89.
- Jamar F, Barone R, Mathieu I, Walrand S, Labar D, Carlier P, et al. 86Y-DOTA0)-D-Phe1-Tyr3-octreotide (SMT487)—a phase 1 clinical study: pharmacokinetics, biodistribution and renal protective effect of different regimens of amino acid co-infusion. Eur J Nucl Med Mol Imaging. 2003 Apr;30(4):510–8.
- Garske-Román U, Sandström M, Fröss Baron K, Lundin L, Hellman P, Welin S, et al. Prospective observational study of 177Lu-DOTA-octreotate therapy in 200 patients with advanced metastasized neuroendocrine tumours (NETs): feasibility and impact of a dosimetry-guided study protocol on outcome and toxicity. Eur J Nucl Med Mol Imaging. 2018 Jun;45(6):970–88.
- Svensson J, Rydén T, Hagmarker L, Hemmingsson J, Wängberg B, Bernhardt P. A novel planar image-based method for bone marrow dosimetry in (177)Lu-DOTATATE treatment correlates with haematological toxicity. EJNMMI Phys. 2016 Dec;3(1):21.
- Pöge U, Gerhardt T, Palmedo H, Klehr HU, Sauerbruch T, Woitas RP. MDRD equations for estimation of GFR in renal transplant recipients. Am J Transplant. 2005 Jun;5(6):1306–11.
- Bergsma H, Konijnenberg MW, Kam BL, Teunissen JJ, Kooij PP, de Herder WW, et al. Subacute haematotoxicity after PRRT with (177)Lu-DOTA-octreotate: prognostic factors, incidence and course. Eur J Nucl Med Mol Imaging. 2016 Mar;43(3):453–63.
- Leimgruber A, Möller A, Everitt SJ, Chabrot M, Ball DL, Solomon B, et al. Effect of Platinum-Based Chemoradiotherapy on Cellular Proliferation in Bone Marrow and Spleen, Estimated by (18)F-FLT PET/CT in Patients with Locally Advanced Non-Small Cell Lung Cancer. J Nucl Med. 2014 Jul;55(7):1075–80.
- Rendon DA, Kotedia K, Afshar SF, Punia JN, Sabek OM, Shirkey BA, et al. Mapping Radiation Injury and Recovery in Bone Marrow Using 18F-FLT PET/CT and USPIO MRI in a Rat Model. J Nucl Med. 2016 Feb;57(2):266–71.
- Roberts J, Chen B, Curtis LM, Agarwal A, Sanders PW, Zinn KR. Detection of early changes in renal function using 99mTc-MAG3 imaging in a murine model of ischemia-reperfusion injury. Am J Physiol Renal Physiol. 2007 Oct;293(4):F1408–12.
- Herrler T, Wang H, Tischer A, Bartenstein P, Jauch KW, Guba M, et al. 99mTc-MAG3 scintigraphy for the longitudinal follow-up of kidney function in a mouse model of renal ischemia-reperfusion injury. EJNMMI Res. 2012 Jan;2(1):2.
- Ilhan H, Wang H, Gildehaus FJ, Wängler C, Herrler T, Todica A, et al. Nephroprotective effects of enalapril after [177Lu]-DOTATATE therapy using serial renal scintigraphies in a murine model of radiation-induced nephropathy. EJNMMI Res. 2016 Dec;6(1):64.
- Melis M, de Swart J, de Visser M, Berndsen SC, Koelewijn S, Valkema R, et al. Dynamic and static small-animal SPECT in rats for monitoring renal function after 177Lu-labeled Tyr3-octreotate radionuclide therapy. J Nucl Med. 2010 Dec;51(12):1962–8.
- Bubeck B, Brandau W, Weber E, Kälble T, Parekh N, Georgi P. Pharmacokinetics of technetium-99m-MAG3 in humans. J Nucl Med. 1990 Aug;31(8):1285–93.
- Rutland M, Que L, Hassan IM. “FUR”–one size suits all. Eur J Nucl Med. 2000 Nov;27(11):1708–13.
- Patlak CS, Blasberg RG. Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data. Generalizations. J Cereb Blood Flow Metab. 1985 Dec;5(4):584–90.
- Shields AF, Grierson JR, Dohmen BM, Machulla HJ, Stayanoff JC, Lawhorn-Crews JM, et al. Imaging proliferation in vivo with [F-18]FLT and positron emission tomography. Nat Med. 1998 Nov;4(11):1334–6.
- Johnbeck CB, Knigge U, Langer SW, Loft A, Berthelsen AK, Federspiel B, et al. Prognostic Value of 18F-FLT PET in Patients with Neuroendocrine Neoplasms: A Prospective Head-to-Head Comparison with 18F-FDG PET and Ki-67 in 100 Patients. J Nucl Med. 2016 Dec;57(12):1851–7.
Article / Publication Details
Received: December 31, 2018
Accepted: April 17, 2019
Published online: April 19, 2019
Issue release date: January 2020
Number of Print Pages: 9
Number of Figures: 4
Number of Tables: 0
ISSN: 0028-3835 (Print)
eISSN: 1423-0194 (Online)
For additional information: https://www.karger.com/NEN
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
Get Permission
PubMed ID
