Top

Published in:

Open Access 01-12-2014 | Original research

Biodistribution and radiodosimetry of a novel myocardial perfusion tracer ¹²³I-CMICE-013 in healthy rats

Authors: Yin Duan, Julia Lockwood, Lihui Wei, Chad Hunter, Karen Soueidan, Corinne Bensimon, Pasan Fernando, R Glenn Wells, Terrence D Ruddy

Published in: EJNMMI Research | Issue 1/2014

Abstract

Background

¹²³I-CMICE-013 is a novel radiotracer previously reported to have promising characteristics for single-photon emission computed tomography (SPECT) myocardial perfusion imaging. We evaluated the biokinetics and radiodosimetry of this rotenone-like ¹²³I-labeled tracer in a microSPECT imaging-based study.

Methods

37 to 111 MBq of ¹²³I-CMICE-013 was synthesized and administered intravenously to 14 healthy rats. Images were acquired with a microSPECT/CT camera at various time intervals and reconstructed to allow activity quantification in the tissues of interest. Radiation dosage resulted from the injection of ¹²³I-CMICE-013 was estimated base on the biodistribution data. Tissue uptake values from image analysis were verified by gamma-counting dissected organs ex vivo.

Results

The heart/stomach and heart/intestine uptake ratios peaked shortly after the injection of ¹²³I-CMICE-013, meanwhile the heart/liver ratio reached 2 as early as at 23 min post-injection. Little activity was observed in the lung and overnight clearance was significant in most of the measured tissues. The radiation dosimetry analysis based on the time-activity curves provided an estimate of the effective human dose of 6.99E-03 mSv/MBq using ICRP 60 and 7.15E-03 mSv/MBq using ICRP 103, which is comparable to the popular myocardium perfusion imaging (MPI) agents such as ^99mTc-tetrofosmin and ^99mTc-sestamibi, as well as other ¹²³I-based radiotracers.

Conclusions

¹²³I-CMICE-013 demonstrated desirable characteristics in its biokinetic and radiodosimetric profiles, supporting its potential application as a novel myocardial perfusion imaging agent.

Available only for authorised users

Salerno M, Beller G: Noninvasive assessment of myocardial perfusion. Circ Cardiovasc Imaging 2009, 2: 412–424.CrossRefPubMed

Baggish AL, Boucher CA: Radiopharmaceutical agents for myocardial perfusion imaging. Circulation 2008, 118: 1668–1674.CrossRefPubMed

Wackers FJT, Berman DS, Maddahi J, Watson DD, Beller GA, Strauss HW, Boucher CA, Picard M, Holman BL, Fridrich R, Inglese E, Delaloye B, Bischof-Delaloye A, Camin L, McKusick K: Technetium-99 m hexakis 2-methoxyisobutyl isonitrile: human biodistribution, dosimetry, safety, and preliminary comparison to thallium-201 for myocardial perfusion imaging. J Nucl Med 1989, 30: 301–311.PubMed

Higley B, Smith FW, Smith T, Gemmell HG, Gvozdanovic DV, Graham D, Hinge D, Davidson J, Lahiri A: Technetium-99 m-1,2-bis[bis(2-ethoxyethyl)phosphino]ethane: human biodistribution, dosimetry and safety of a new myocardial perfusion imaging agent. J Nucl Med 1993, 34: 30–38.PubMed

International Commission on Radiological Protection: Radiation dose to patients from radiopharmaceuticals. ICRP Publication 80: Addendum to ICRP Publication 53. Ann. ICRP 1998., 28(3):

Wei L, Bensimon C, Lockwood J, Yan X, Fernando P, Wells RG, Duan Y, Chen Y-X, Redshaw R, Covitz PA, Ruddy TD: Synthesis and characterization of ¹²³I-CMICE-013: a potential SPECT myocardial perfusion imaging agent. Bioorg Med Chem 2013, 21: 2903–2911.CrossRefPubMed

Stabin MG: Fundamentals of Nuclear Medicine Dosimetry. New York: Springer; 2008.

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.PubMed

International Commission on Radiological Protection: 1990 Recommendations of the International Commission on Radiological Protection. ICRP Publication 60. Ann. ICRP 1991., 21(1–3):

10.

International Commission on Radiological Protection: Adult reference computational phantoms. ICRP Publication 110. Ann. ICRP 2009., 39(2):

11.

International Commission on Radiological Protection: The 2007 recommendations of the international commission on radiological protection. ICRP Publication 103. Ann. ICRP 2007., 37(2–4):

12.

VanBrocklin HF, Hanrahan SM, Enas JD, Nandanan E, O'Neil JP: Mitochondrial avid radioprobes. Preparation and evaluation of 7′( Z )-[¹²⁵I]iodorotenone and 7′( Z )-[¹²⁵I]iodorotenol. Nucl Med Biol 2007, 34: 109–116.PubMedCentralCrossRefPubMed

13.

Hatada K, Riou LM, Ruiz M, Yamamichi Y, Duatti A, Lima RL, Goode AR, Watson DD, Beller GA, Glover DK: ^99mTc-N-DBODC5, a new myocardial perfusion imaging agent with rapid liver clearance: comparison with ^99mTc-sestamibi and ^99mTc-tetrofosmin in rats. J Nucl Med 2004, 45: 2095–2101.PubMed

14.

Kesner AL, Hsueh W-A, Czernin J, Padgett H, Phelps ME, Silverman DHS: Radiation dose estimates for [¹⁸F]5-fluorouracil derived from PET-based and tissue-based methods in rats. Mol Imaging Biol 2014, 10: 341–348.CrossRef

15.

Bretin F, Warnock G, Bahri MA, Aerts J, Mestdagh N, Buchanan T, Valade A, Mievis F, Giacomelli F, Lemaire C, Luxen A, Salmon E, Seret A, Plenevaux A: Preclinical radiation dosimetry for the novel SV2A radiotracer [¹⁸F]UCB-H. EJNMMI Res 2013, 3: 35.PubMedCentralCrossRefPubMed

16.

Broisat A, Ruiz M, Goodman NC, Hanrahan SM, Reutter BW, Brennan KM, Janabi M, Schaefer S, Watson DD, Beller GA, VanBrocklin HF, Glover DK: Myocardial uptake of 7′-( Z )-[¹²³I]iodorotenone during vasodilator stress in dogs with critical coronary stenoses. Circ Cardiovasc Imaging 2011, 4: 685–692.PubMedCentralCrossRefPubMed

17.

Tavares AAS, Batis JC, Papin C, Jennings D, Alagille D, Russell DS, Vala C, Lee H, Baldwin RM, Zubal IG, Marek KL, Seibyl JP, Barret O, Tamagnan GD: Kinetic modeling, test-retest, and dosimetry of ¹²³I-MNI-420 in humans. J Nucl Med 2013, 54: 1760–1767.CrossRefPubMed

18.

Kuikka JT, Bergström KA, Ahonen A, Länsimies E: The dosimetry of iodine-123 labelled 2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane. Eur J Nucl Med 1994, 21: 53–56.PubMed

19.

Lin K-J, Liu C-Y, Wey S-P, Hsiao I-T, Wu J, Fu Y-K, Yen T-C: Brain SPECT imaging and whole-body biodistribution with [¹²³I]ADAM - a serotonin transporter radiotracer in healthy human subjects. Nucl Med Biol 2006, 33: 193–202.CrossRefPubMed

20.

Kupinski MA, Barrett H: (Eds): Small-Animal Spect Imaging. New York: Springer; 2005.CrossRef

21.

Golestani R, Wu C, Tio RA, Zeebregts CJ, Petrov AD, Beekman FJ, Dierckx RA, Boersma HH, Slart RH: Small-animal SPECT and SPECT/CT: application in cardiovascular research. Eur J Nucl Med Mol Imaging 2010, 37: 1766–1777.PubMedCentralCrossRefPubMed

22.

Garcia EV: Physical attributes, limitations, and future potential for PET and SPECT. J Nucl Cardiol 2012, 19(Suppl 1):S19-S29.CrossRefPubMed

23.

Erlandsson K, Buvat I, Pretorius PH, Thomas BA, Hutton BF: A review of partial volume correction techniques for emission tomography and their applications in neurology, cardiology and oncology. Phys Med Biol 2012, 57: R119-R159.CrossRefPubMed

24.

Even-Sapir E, Keidar Z, Bar-Shalom R: Hybrid imaging (SPECT/CT and PET/CT)–improving the diagnostic accuracy of functional/metabolic and anatomic imaging. Semin Nucl Med 2009, 39: 264–275.CrossRefPubMed

25.

Vanhove C, Defrise M, Bossuyt A, Lahoutte T: Improved quantification in multiple-pinhole SPECT by anatomy-based reconstruction using microCT information. Eur J Nucl Med Mol Imaging 2011, 38: 153–165.CrossRefPubMed

26.

Li S, Sinusas AJ, Dobrucki LW, Liu Y-H: New approach to quantification of molecularly targeted radiotracer uptake from hybrid cardiac SPECT/CT: methodology and validation. J Nucl Med 2013, 54: 2175–2181.CrossRefPubMed

Title: Biodistribution and radiodosimetry of a novel myocardial perfusion tracer 123I-CMICE-013 in healthy rats
Authors: Yin Duan
Julia Lockwood
Lihui Wei
Chad Hunter
Karen Soueidan
Corinne Bensimon
Pasan Fernando
R Glenn Wells
Terrence D Ruddy
Publication date: 01-12-2014
Publisher: Springer Berlin Heidelberg
Published in: EJNMMI Research / Issue 1/2014
Electronic ISSN: 2191-219X
DOI: https://doi.org/10.1186/2191-219X-4-16

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Biodistribution and radiodosimetry of a novel myocardial perfusion tracer ¹²³I-CMICE-013 in healthy rats

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2014

Multiparametric magnetic resonance in the assessment of the gender differences in a high-grade glioma rat model

Identification of positron emission tomography (PET) tracer candidates by prediction of the target-bound fraction in the brain

Evaluation of retinol binding protein 4 and carbamoylated haemoglobin as potential renal toxicity biomarkers in adult mice treated with 177Lu-octreotate

Test-retest variability of adenosine A2A binding in the human brain with 11C-TMSX and PET

Imaging VEGF receptor expression to identify accelerated atherosclerosis

Optimising the radiolabelling properties of technetium tricarbonyl and His-tagged proteins