Simultaneous dual-tracer 99mTc-tetrofosmin and 123I-BMIPP acquisition with CZT for ischemic memory: The future approaches to image the past

  • Carmela Nappi
  • Valeria Gaudieri
  • Mario PetrettaEmail author

So far, cadmium-zinc-telluride (CZT) detectors technology did not disappoint the expectations and what we believed could be realized with the advent of CZT cameras for cardiac imaging is now a reality.1,2 The hardware implementation of this equipment with regard to traditional Anger camera consists in the utilization of CZT modules on a column of tungsten collimators rather than lead. CZT semiconductors operate at room temperature and can process > 10 million photons/second/mm2 boasting the highest energy resolution among all the commercially available scintillators.3 In addition, lead elimination from the detector suite avoids the potential X-ray generation, which can degrade image quality. The application of this system allows higher energy and spatial resolution with narrower photo-peak energy windows as compared to conventional Anger cameras.4 As estimated, the advantageous characteristics of this novel technology provide dose reduction and acquisition time shortening with improved patient comfort and compliance and high diagnostic accuracy.2,5 These characteristics answer to the current dose-optimization challenge as also demonstrated by recent introduction of new iterative algorithms for conventional gamma cameras.6

Two industries applied CZT method by developing different geometry configuration (D-SPECT, Spectrum Dynamics, Palo Alto, CA, USA; Discovery NM 530c, and the hybrid version NM/CT 570c GE Healthcare, Haifa, Israel). Interestingly, the original cardiac dedicated approach imaging of D-SPECT system spread out to other applications such as thyroid and parathyroid imaging.7 Indeed, CZT concept showed such powerful strengths that manufactories made a great effort in developing general purpose SPECT scanners. Therefore, VERITION™ model has been released by Spectrum Dynamics while Discovery NM/CT 670 CZT has been proposed by GE Healthcare. For this latter device, in the present issue of the Journal8 Yamada et al. explored the feasibility of simultaneous 99mTc-tetrofosmin and 123I-β-methyliodo-phenyl pentadecanoic acid (123I-BMIPP) dual-tracer imaging. The idea to perform dual-isotope imaging has deep roots.9 Indeed, simultaneous dual-tracer protocols offer the advantage of decreasing potential image misalignment and further reducing acquisition time, detecting in one examination two target patterns, such as perfusion by 99mTc-sestamibi and innervation by 123I- metaiodobenzylguanidine (MIBG), or two faces of the same coin such as 201Tl and 99mTc-sestamibi stress-rest imaging to evaluate myocardial viability and perfusion. Besides cardiac imaging, simultaneous dual isotope acquisition possibilities have been explored for different applications as for brain,10 and oncological imaging.11 However, its realization has been extremely demanding, due to conventional gamma camera limitations, such as the consistent cross-contamination between different isotope energy windows. The cross-contamination issue has a much higher impact as the energy windows are closer.12 In particular, 99mTc photo-peak of 140 keV is very near to the 123I one, which is 159 keV. The introduction of CZT solid state cameras, permitting better photon energy discrimination, has reignited the interest in dual-isotope imaging setting-up.13,14 Even if the downscatter fraction from the higher peak into the lower still affects the count rate estimation,15 the availability of correction methods allows to extract images with better contrast for both 99mTc and 123I.16 Some studies already investigated the feasibility of simultaneous dual-tracer imaging with CZT cameras.17,18 Yamada et al.8 study fits in this research field investigating ischemic memory evaluation by using the novel design Discovery NM/CT 670 CZT with simultaneous rest 99mTc-tetrofosmin and 123I-BMIPP imaging. They compared the dual-tracer protocol with each single-tracer acquisition in thirty patients with previous myocardial infarction undergone primary coronary percutaneous intervention. They found that quantitative and semi quantitative values of global and regional left ventricle perfusion, function and fatty acid metabolism obtained by simultaneous dual-tracer protocol were comparable with those obtained by each single tracer modality, suggesting that the proposed protocol is feasible in clinical routine. The evaluation of perfusion-metabolism mismatch may detect jeopardized myocardium after an ischemic event. BMIPP is an analogue of 15-(p-iodophenyl) pentadecanoic acid. Rest imaging of 123I-BMIPP is related to its metabolism in the mitochondria and its uptake during myocardial ischemia occurrence is dynamic. During the acute phase (1-6 h), the amount of the intracellular non-oxidized fatty acid pool rises with an increased 123I-BMIPP uptake. Starting from the subacute phase (> 6 h), there is a reduction of 123I-BMIPP uptake in the ischemia territory, and it recovers in the chronic phase (30 days).19 Therefore, the use of fatty acid radiotracers may capture recently occurred ischemia, without the need for a provocative test examination depicting ischemic memory. The comparison of 123I-BMIPP findings with rest perfusion uptake offers three different patterns. The presence of a negative match result depicts physiological uptake distribution as expression of viable and perfused myocardium. The presence of a matched uptake defect identifies a region of injured myocardium that will not recover after revascularization. The mismatch between myocardial metabolism and perfusion can be attributed to regions of viable myocardium with abnormal fatty acid metabolism predicting potential full recovery with time. However, only a few number of studies investigate the prognostic impact of perfusion metabolism mismatch reporting that, discordant 123I BMIPP uptake is an excellent predictor of future cardiac events.

The improved energy and spatial resolution of implemented CZT detectors opens the way to such imaging protocol proposal. Indeed, the evaluation of perfusion-metabolism mismatch may translate into a concept with a double meaning across the past to the future: imaging can be thought as a footprint to recall past ischemic events as well as a tool for providing information to predict outcome. In order to save out of the time an image, an event, a phenomenon, human being used more and more complex instruments, passing from watercolours paintings to the first films to digital cameras. In the same way, technological innovation has allowed medicine to photograph receptor and metabolic patterns, contributing not only to the diagnosis but also to the deeper knowledge of diseases. The recent hardware and radiopharmaceutical developments are offering new perspectives, for example the identification of ischemic memory by dual isotope imaging with CZT detectors, helping us to predict the future not only by shooting the present but also by investigating the past.

It remains to be evaluated the real clinical impact of information derived from this imaging protocol, identifying the category of patients that may most benefit from this diagnostic approach method. In fact, the Yamada’s study8 is a single-center, observational report including a small number of patients without outcome measures. Moreover, from Figsures 2 and 3 of Yamadas’s study, one patient with a severely dilated left ventricle showed a prominent discrepancy between the single- and dual-tracer results and another revealed discrepant results in the QPS for BMIPP, suggesting a failure in the quantitative perfusion SPECT processing to adjust the endocardial/epicardial contour. Finally, in the era of artificial intelligence,20 there is to examine whether data obtained by such a diagnostic work-up may contribute in tailored therapeutic strategies modifying patient outcome and if there is space of future applicability of these information to machine learning.



None of the authors has financial conflicts of interest.


  1. 1.
    Gambhir SS, Berman DS, Ziffer J, Nagler M, Sandler M, Patton J, et al. A novel high-sensitivity rapid-acquisition single-photon cardiac imaging camera. J Nucl Med 2009;50(4):635-43.CrossRefGoogle Scholar
  2. 2.
    Chowdhury FU, Vaidyanathan S, Bould M, Marsh J, Trickett C, Dodds K, et al. Rapid-acquisition myocardial perfusion scintigraphy (MPS) on a novel gamma camera using multipinhole collimation and miniaturized cadmium-zinc-telluride (CZT) detectors: Prognostic value and diagnostic accuracy in a ‘real-world’ nuclear cardiology service. Eur Heart J Cardiovasc Imaging 2014;15(3):275-83.CrossRefGoogle Scholar
  3. 3.
    Sharir T, Slomka PJ, Berman DS. Solid-state SPECT technology: Fast and furious. J Nucl Cardiol 2010;17(5):890-6.CrossRefGoogle Scholar
  4. 4.
    Niimi T, Nanasato M, Sugimoto M, Maeda H. Evaluation of cadmium-zinc-telluride detector-based single-photon emission computed tomography for nuclear cardiology: A comparison with conventional anger single-photon emission computed tomography. Nucl Med Mol Imaging 2017;51(4):331-7.CrossRefGoogle Scholar
  5. 5.
    Lecchi M, Malaspina S, Scabbio C, Gaudieri V, Del Sole A. Myocardial perfusion scintigraphy dosimetry: Optimal use of SPECT and SPECT/CT technologies in stress-first imaging protocol. Clin Transl Imaging 2016;4(6):491-8.CrossRefGoogle Scholar
  6. 6.
    Nappi C, Acampa W, Nicolai E, Daniele S, Zampella E, Assante R, et al. Long-term prognostic value of low-dose normal stress-only myocardial perfusion imaging by wide beam reconstruction: A competing risk analysis. J Nucl Cardiol 2018. Scholar
  7. 7.
    Miyazaki Y, Kato Y, Imoto A, Fukuchi K. Imaging of the thyroid and parathyroid using a cardiac cadmium zinc telluride camera: Phantom studies. J Nucl Med Technol 2017. Scholar
  8. 8.
    Yamada Y, Nakano S, Gatate Y, Okano N, Muramatsu T, Nishimura S, et al. Feasibility of simultaneous (99 m)Tc-tetrofosmin and (123)I-BMIPP dual-tracer imaging with cadmium-zinc-telluride detectors in patients undergoing primary coronary intervention for acute myocardial infarction. J Nucl Cardiol 2019. Scholar
  9. 9.
    Berman DS, Kiat H, Friedman JD, Wang FP, van Train K, Matzer L, et al. Separate acquisition rest thallium-201/stress technetium-99 m sestamibi dual-isotope myocardial perfusion single-photon emission computed tomography: A clinical validation study. J Am Coll Cardiol 1993;22:1455-64.CrossRefGoogle Scholar
  10. 10.
    El Fakhri G, Moore SC, Maksud P, Aurengo A, Kijewski MF. Absolute activity quantitation in simultaneous 123I/99 mTc brain SPECT. J Nucl Med 2001;42(2):300-8.Google Scholar
  11. 11.
    Rakvongthai Y, El Fakhri G, Lim R, Bonab AA, Ouyang J. Simultaneous 99 mTc-MDP/123I-MIBG tumor imaging using SPECT-CT: Phantom and constructed patient studies. Med Phys 2013;40(10):102506. Scholar
  12. 12.
    Zampella E, Nappi C, Acampa W. Simultaneous dual isotope (201) Tl/(99m)Tc myocardial perfusion imaging using CZT cameras: Clinical utility or technical challenge? J Nucl Cardiol 2018. Scholar
  13. 13.
    Bellevre D, Manrique A, Legallois D, Bross S, Baavour R, Roth N, et al. First determination of the heart-to-mediastinum ratio using cardiac dual isotope (123I-MIBG/99mTc-tetrofosmin) CZT imaging in patients with heart failure: The ADRECARD study. Eur J Nucl Med Mol Imaging 2015;42:1912-9.CrossRefGoogle Scholar
  14. 14.
    Blaire T, Bailliez A, Ben Bouallegue F, Bellevre D, Agostini D, Manrique A. First assessment of simultaneous dual isotope ((123) I/(99m) Tc) cardiac SPECT on two different CZT cameras: A phantom study. J Nucl Cardiol 2018;25(5):1692-704.CrossRefGoogle Scholar
  15. 15.
    Marcassa C, Zoccarato O. Multi-peak multi-isotopes myocardial SPECT: It’s easier said than done. J Nucl Cardiol 2018. Scholar
  16. 16.
    Holstensson M, Erlandsson K, Poludniowski G, Ben-Haim S, Hutton BF. Model-based correction for scatter and tailing effects in simultaneous 99mTc and 123I imaging for a CdZnTe cardiac SPECT camera. Phys Med Biol 2015;60(8):3045-63.CrossRefGoogle Scholar
  17. 17.
    Songy B, Guernou M, Lussato D, Queneau M, Bonardel G, Grellier JF, et al. Feasibility of simultaneous dual isotope acquisition for myocardial perfusion imaging with a cadmium zinc telluride camera. J Nucl Cardiol 2018. Scholar
  18. 18.
    Barone-Rochette G, Zoreka F, Djaileb L, Piliero N, Calizzano A, Quesada JL, et al. Diagnostic value of stress thallium-201/rest technetium-99m-sestamibi sequential dual isotope high-speed myocardial perfusion imaging for the detection of haemodynamically relevant coronary artery stenosis. J Nucl Cardiol 2018. Scholar
  19. 19.
    Messina SA, Aras O, Dilsizian V. Delayed recovery of fatty acid metabolism after transient myocardial ischemia: A potential imaging target for “ischemic memory”. Curr Cardiol Rep 2007;9(2):159-65.CrossRefGoogle Scholar
  20. 20.
    Nappi C, Cuocolo A. The machine learning approach: Artificial intelligence is coming to support critical clinical thinking. J Nucl Cardiol 2018. Scholar

Copyright information

© American Society of Nuclear Cardiology 2019

Authors and Affiliations

  • Carmela Nappi
    • 1
  • Valeria Gaudieri
    • 1
  • Mario Petretta
    • 2
    Email author
  1. 1.Department of Advanced Biomedical SciencesUniversity Federico IINaplesItaly
  2. 2.Department of Translational Medical SciencesUniversity Federico IINaplesItaly

Personalised recommendations