Scintigraphic Analysis Essay


The objective of this work is to evaluate the potential effect of cardiac stress exercise on the accumulation of [123I]IAZA, a radiopharmaceutical used to image focal tissue hypoxia, in otherwise normal myocardium in healthy volunteers, and to determine the impact of exercise on [123I]IAZA pharmacokinetics. The underlying goal is to establish a rational basis and a baseline for studies of focal myocardial hypoxia in cardiac patients using [123I]IAZA. Three healthy male volunteers ran the ‘Bruce’ treadmill protocol, a clinically-accepted protocol designed to expose myocardial ischemia in patients. The ‘Bruce’ criterion heart rate is 85% of [220–age]. Approximately one minute before reaching this level, [123I]IAZA (5.0 mCi/0.85 mg) was administered as a slow (1–3 min) single intravenous (i.v.) injection via an indwelling venous catheter. The volunteer continued running for an additional 1 min before being transferred to a gamma camera. Serum samples were collected from the arm contralateral to the administration site at pre-determined intervals from 1 min to 45 h post injection and were analyzed by radio HPLC. Pharmacokinetic (PK) parameters were derived for [123I]IAZA and total radioactivity (total[123I]) using compartmental and noncompartmental analyses. Whole-body planar scintigraphic images were acquired from 0.75 to 24 h after dosing. PK data and scintigraphic images were compared to previously published [123I]IAZA data from healthy volunteers rest. Following exercise stress, both [123I]IAZA and total[123I] exhibited bi-exponential decline profiles, with rapid distribution phases [half-lives (t1/2α) of 1.2 and 1.4 min, respectively], followed by slower elimination phases [t1/2β of 195 and 290 min, respectively]. Total body clearance (CLTB) and the steady state volume of distribution (Vss) were 0.647 L/kg and 185 mL/min, respectively, for [123I]IAZA and 0.785 L/kg and 135 mL/min, respectively, for total[123I]. The t1/2β, CLTB and Vss values were comparable to those reported previously for rested volunteers. The t1/2α was approximately 4-fold shorter for [123I]IAZA and approximately 3-fold shorter for total[123I] under exercise relative to rested subjects. The heart region was visualized in early whole body scintigraphic images, but later images showed no accumulated radioactivity in this region, and no differences from images reported for rested volunteers were apparent. Minimal uptake of radiotracer in myocardium and skeletal muscle was consistent with uptake in non-stressed myocardium. Whole-body scintigrams for [123I]IAZA in exercise-stressed healthy volunteers were indistinguishable from images of non-exercised volunteers. There was no evidence of hypoxia-dependent binding in exercised but otherwise healthy myocardium, supporting the conclusion that exercise stress at Bruce protocol intensity does not induce measurable myocardial hypoxia. Effects of exercise on PK parameters were minimal; specifically, the t1/2α was shortened, reflecting increased cardiac output associated with exercise. It is concluded that because [123I]IAZA was not metabolically bound in exercise-stressed myocardium, a stress test will not create elevated myocardial background that would mask regions of myocardial perfusion deficiency. [123I]IAZA would therefore be suitable for the detection of viable, hypoxic myocardium in patients undergoing stress-test-based diagnosis. View Full-Text

Keywords: pharmacokinetics; radiotracers; hypoxia; nuclear imaging; [123I]IAZApharmacokinetics; radiotracers; hypoxia; nuclear imaging; [123I]IAZA

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MDPI and ACS Style

Stypinski, D.; McQuarrie, S.A.; McEwan, A.J.B.; Wiebe, L.I. Pharmacokinetics and Scintigraphic Imaging of the Hypoxia-Imaging Agent [123I]IAZA in Healthy Adults Following Exercise-Based Cardiac Stress. Pharmaceutics2018, 10, 25.

AMA Style

Stypinski D, McQuarrie SA, McEwan AJB, Wiebe LI. Pharmacokinetics and Scintigraphic Imaging of the Hypoxia-Imaging Agent [123I]IAZA in Healthy Adults Following Exercise-Based Cardiac Stress. Pharmaceutics. 2018; 10(1):25.

Chicago/Turabian Style

Stypinski, Daria; McQuarrie, Stephen A.; McEwan, Alexander J.B.; Wiebe, Leonard I. 2018. "Pharmacokinetics and Scintigraphic Imaging of the Hypoxia-Imaging Agent [123I]IAZA in Healthy Adults Following Exercise-Based Cardiac Stress." Pharmaceutics 10, no. 1: 25.

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1. Russe RR, Zaret BL. Nuclear cardiology: Present and future. Curr Probl Cardiol. 2006;31:557–629.[PubMed]

2. Hendel RC, Berman DS, Di Carli MF, Heidenreich PA, Henkin RE, Pellikka PA, et al. ACCF/ASNC/ACR/AHA/ASE/SCCT/SCMR/SNM 2009 appropriate use criteria for cardiac radionuclide imaging: A report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, the American Society of Nuclear Cardiology, the American College Radiology, the American Heart Association, the American Society of Echocardiography, the Society of Cardiovascular Computed Tomograph the Society for Cardiovascular Magnetic Resonance, and the Society of Nuclear Medicine, endorsed by the American College of Emergency Physicians. Circulation. 2009;119:e561–87.[PubMed]

3. Lapeyre AC, 3rd, Goraya TY, Johnston DL, Gibbons RJ. The impact of Caffeine on vasodilator stress perfusion studies. J Nucl Cardiol. 2004;11:506–11.[PubMed]

4. Kharabsheh SM, Al-Sugair A, Al-Buraiki J, Al-Farhan J. Overview of exercise stress testing. Ann Saudi Med. 2006;26:1–6.[PubMed]

5. Albro PC, Gould KL, Westcott RJ, Hamilton GW, Ritchie JL, Williams DL, et al. Noninvasive assessment of coronary stenoses by myocardial imaging during pharmacologic coronary vasodilatation.III. Clinical trial. Am J Cardiol. 1978;42:751–60.[PubMed]

6. Sonneblick EH, Fishman WH, LeJemetel TH. Dobutamine a new synthetic cardiaoactive sympathetic amines. N Eng J Med. 1979;300:17–22.[PubMed]

7. Weich HF, Strauss HW, Pitt B. The Extraction of TL-201 by the myocardium. Circulation. 1977;56:188–91.[PubMed]

8. Beller GA, Watson DD. Physiological basis of myocardial perfusion imaging with technetium99m agents. Semin Nucl Med. 1991;12:173.[PubMed]

9. Taillefer R, Gagnon A, Laflamme L, Grégoire J, Léveillé J, Phaneuf DC. Same day injections of tc99m methoxy isobutyl isonitrile (hexamibi) for myocardial tomographic imaging: Comparison between rest-stress and stress-rest injection sequences. Eur J NuclMed. 1989;15:113–7.[PubMed]

10. Husain SS. Myocardial perfusion imaging protocols: Is there an ideal protocol? J Nucl Med Technol. 2007;35:3–9.[PubMed]

11. Holly TA, Abbott BG, Al-Mallah M, Calnon DA, Cohen MC, DiFilippo FP, et al. Imaging guidelines for nuclear cardiology procedures. Menu: Manage your practice: Guidelines and standards. [Last accessed on 2010 Jun]. Available from: .

12. Hendel RC, Corbett JR, Cullom SJ, DePuey EG, Garcia EV, Bateman TM. The value and practice of attenuation correction for myocardial perfusion SPECT imaging: A joint position statement from the American Society of Nuclear Cardiology and the Society of Nuclear Medicine. J Nucl Med. 2002;43:273–80.[PubMed]

13. Hendel RC. Attenuation correction: Eternal dilemma or real improvement? Q J Nucl Med Mol Imaging. 2005;49:30–42.[PubMed]

14. Mettler FA, Guiberteau MJ. 5th ed. Amsterdam: Saunders-Elsevier; 2006. Essential of Nuclear Medicine Imaging; pp. 101–40.

15. Cerqueira MD, Weissman NJ, Dilsizian V, Jacobs AK, Kaul S, Laskey WK, et al. Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart: A statement for healthcare professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association. J Nucl Cardiol. 2002;9:240–5.[PubMed]

16. Hachamovitch R, Berman DS, Shaw LJ, Kiat H, Cohen I, Cabico JA, et al. Incremental prognostic value of myocardial perfusion single photon emission computed tomography for the prediction of cardiac death: Differential stratification for risk of cardiac death and myocardial infarction. Circulation. 1998;97:535–43.[PubMed]

17. Berman DS, Kang X, Van Train KF, Lewin HC, Cohen I, Areeda J, et al. Comparative prognostic value of automatic quantitative analysis versus Semiquantitative visual analysis of exercise myocardial perfusion single-photon emission computed tomography. J Am Coll Cardiol. 1998;32:1987–95.[PubMed]

18. Cullom SJ, Case JA, Bateman TM. Electrocardiographically gated myocardial perfusion SPECT: Technical principles and quality control considerations. J Nucl Cardiol. 1998;5:418–25.[PubMed]

19. Smanio PE, Watson DD, Segalla DL, Vinson EL, Smith WH, Beller GA. Value of gating of technetium-99m sestamibi singlephoton emission computed tomographic imaging. J Am Coll Cardiol. 1997;30:1687–92.[PubMed]

20. Burrell S, MacDonald A. Artifacts and pitfalls in myocardial perfusion imaging. J Nucl Med Technol. 2006;34:193–211.[PubMed]

21. Cooper JA, Neumann PH, McCandless BK. Effect of patient motion on tomographic myocardial perfusion imaging. J Nucl Med. 1992;33:1566–71.[PubMed]

22. van Dongen AJ, van Rijk PP. Minimizing liver, bowel, and gastric activity in myocardial perfusion SPECT. J Nucl Med. 2000;41:1315–7.[PubMed]

23. Miles J, Cullom SJ, Case JA. An introduction to attenuation correction. J Nucl Cardiol. 1999;6:449–57.[PubMed]

24. Burns RJ, Galligan L, Wright LM, Lawand S, Burke RJ, Gladstone PJ. Improved specificity of myocardial thallium-201 single-photon emission computed tomography in patients with left bundle branch block by dipyridamole. Am J Cardiol. 1991;68:504–8.[PubMed]

25. DePuey EG, Guertler-Krawczynska E, Perkins JV, Robbins WL, Whelchel JD, Clements SD. Alteration of myocardial thallium-201 in patients with chronic hypertension undergoing single-photon emission computed tomography. Am J Cardiol. 1988;62:234–8.[PubMed]

26. Galt JR, Germano G. Advances in instrumentation for cardiac SPECT. In: Depuey EG, Berman DS, Garcia EV, editors. Cardiac SPECT imaging. New York: Raven Press; 1995. pp. 91–102.

27. Maddahi J. Myocardial perfusion imaging for the detection and evaluation of coronary artery disease. In: Marcus ML, Schelbert HR, Skorton DJ, Marcus ML, Schelbert HR, Skorton DJ, Wolf GL, et al., editors. Cardiac imagingprinciples and practice. 2nd ed. Philadelphia: WB Saunders; 1996.

28. Frans J, wackers HT. SPECT detection of coronary artery disease. In: Dlisizian V, Narula J, Braunwald E, editors. Atals of Nuclear cardiology. Philadelphia: Current Medicine inc; 2006. pp. 35–66.

29. Brown KA. Prognostic value of thallium-201 myocardial perfusion imaging: A diagnostic tool comes of age. Circulation. 1991;83:363–81.[PubMed]

30. Hachamovitch R, Berman DS, Kiat H, Cohen I, Cabico JA, Friedman J, et al. Exercise myocardial perfusion SPECT in patients without known coronary artery disease.Incremental prognostic value and use in risk stratification. Circulation. 1996;93:905–14.[PubMed]

31. Gibson RS, Watson DD, Craddock GB, Crampton RS, Kaiser DL, Denny MJ, et al. Prediction of cardiac events after uncomplicated myocardial infarction: A prospective study comparing predischarge exercise thallium-201 scintigraphy and coronary angiography. Circulation. 1983;68:321–36.[PubMed]

32. Mahmarian JJ, Mahmarian AC, Marks GF, Pratt CM, Verani MS. Role of adenosine thallium-201 totmography for defrining long term risk in patients after acute myocardial infarction. J am coll cardiology. 1994;25:1333–40.[PubMed]

33. Brown KA, Rowen M. Extent of jeopardized viable myocardium determined by myocardial perfusion imaging best predicts perioperative cardiac events in patients undergoing noncardiac surgery. J Am Coll Cardiol. 1993;21:325–30.[PubMed]

34. Zellweger MJ, Lewin HC, Lai S, Dubois EA, Friedman JD, Germano G, et al. When to stress patients after coronary artery bypass surgery? Risk stratification in patients early and late post-CABG using stress myocardial perfusion SPECT: Implications of appropriate clinical strategies. J Am Coll Cardiol. 2001;37:144–52.[PubMed]

35. Beygui F, Le Feuvre C, Maunoury C, Helft G, Antonietti T, Metzger JP, et al. Detection of coronary restenosis by exercise electrocardiography thallium-201 perfusion imaging and coronary angiography in asymptomatic patients after percutaneous transluminal coronary angioplasty. Am J Cardiol. 2000;1(86):35–40.[PubMed]

36. Shaw L, Berman DS. Sequential single-photon emission computed tomography myocardial perfusion imaging. Am J Cardiol. 2005;17(96):28J–39.[PubMed]

37. Wijns W, Vatner SF, Camici PG. Hibernating myocardium. N Engl J Med. 1998;339:173–81.[PubMed]

38. Beller GA. Noninvasive assessment of myocardial viability. N engl J Med. 2000;343:1488–90.[PubMed]

39. Friedman J, Berman DS, Van Train K, Garcia EV, Bietendorf J, Prigent F, et al. Patient motion in thallium-201 myocardial SPECT imaging.An easily identified frequent source of artifactual defect. Clin Nucl Med. 1988;13:321–4.[PubMed]

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