New SPECT Radiotracers for Myocardial Perfusion Imaging: Major

Developments over Last 5 Years!

f{âtÇz _|â? c{A WAProfessor, School of Health Sciences

Purdue University

Commercial 99mTc Radiotracers for Myocardial Perfusion Imaging

Shortcomings of 99mTc-Sestamibi and 99mTc-Tetrofosmin

1. High Liver Uptake. Despite their widespread clinical application in perfusion imaging, 99mTc-sestamibi and 99mTc-tetrofosmin do not meet the requirements of an ideal perfusion imaging agent, in part due to their high liver uptake. The intense liver uptake, particularly for 99mTc-Sestamibi, makes it difficult to interpret heart activity in the inferior left ventricular wall. Despite intensive efforts to reduce this interference, photon scattering from the high liver activity remains a significant challenge for diagnosis of heart diseases, such as CAD.

2. Relatively low first-pass extraction. High first-pass extraction and linear relationship between the blood flow and radiotracer heart uptake permit better detection of the presence and extent of coronary disease, and more precise delineation of perfusion defects, which is of considerable benefit in managing of patients with known or suspected CAD and assessing risk of future cardiac events (e.g. myocardial infarction and death).

High heart uptake with long myocardial retention

High first-pass extraction with stable myocardial retention, which linearly tracks myocardial blood flow over a wide range

Minimal uptake in the liver and lungs so that images can be taken within 30 min postinjection

Requirements for An Ideal 99mTc Perfusion Radiotracer

PTcP S

S

N

N

N O

O

O O

OOO

+

99mTcN-DBODC

Advantage: high heart uptake with fast clearanceDisadvantage: kit formulation for wide clinical applicationa

99mTcN-DBODC

High quality SPECT images could be obtained within 10 min after injection of 99mTcN-DBODC

99mTc-TMEOPContrast Media Mol. Imaging (2010)

99mTc-Sestamibi 99mTc-Tetrofosmin 99mTc-TMEOP

30 – 35 min

60 – 65 min

Contrast Media Mol. Imaging (2010)

Comparison of Planar Images

Contrast Media Mol. Imaging (2010)

Representative SPECT image analysis at 40 minutes after administration: short axis slices representing (A) 99mTc-TMEOP; (B) 99mTc-sestamibi and (C) 99mTc-tetrofosmin.

99mTc-TMEOP

99mTc-Sestamibi

99mTc-Tetrofosmin

99mTcN-MPO

Comparison of Planar Images

99mTc-Sestamibi

99mTcN-DBODC5

99mTcN-MPO

5 min 15 min 30 min 60 min

Radio-HPLC Chromatograms for 99mTcN-MPO from Different Formulations

2-Vial Formulation Single-Vial Formulation

5 10 15 20 25

mVolt

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5 10 15 20 25

mVolt

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Non-SnCl2 Single-Vial

Formulation

SnCl2-Containing Single-Vial

Formulation

Comparison of Heart Retention and Liver Clearance Kinetics

SD rat injected with 15 mCi of

99mTcN-MPO

Gated SPECT with 99mTcN-MPO

Image acquisition started at 30-60 min

(1.0 mm Filter)

Gated SPECT with 99mTcN-MPO 15 mCi

0-30 min (No Filter)

0-30 min (No Filter)

Gated SPECT with 99mTcN-MPO 15 mCi

0-30 min (No Filter)

Gated SPECT with 99mTcN-MPO 15 mCi

Effect of Filtration on Image Quality0.0 mm 0.3 mm 0.6 mm 1.0 mm

LM1195 PET

SD rat injected with 9 mCi of 99mTcN-MPO

Whole-Body Planar Images (Rest) of 99mTcN-MPO in Healthy Volunteers

10 min 60 min 120 min 240 min

Gao S, Zhao G, Wen Q, Bai L, Chen B, Ji T, Ji B, Ma Q. Pharmacokinetics and Biodistribution of 99mTc N-MPO in Healthy Human Volunteers. Clin Nucl Med. 2013 (in press)

The 60-min SPECT Images with 99mTcN-MPO in Healthy Volunteers

The 60-min SPECT Images of a Patient with Myocardial Infarction

99mTc-Sestamibi

99mTcN-MPO

The 60-min SPECT Images of a Patient with Myocardial Infarction

99mTc-Sestamibi

99mTcN-MPO

Myocardial Localization Mechanism of 99mTcN-MPO

On the basis of radioactivity distribution data, it is clear that 99mTcN-MPO have the same myocardial localization mechanism as that of 99mTc-Sestamibi.

0 20 40 60 80

Supernatant I

Supernatant II

Fragment

Mitochndria

% Total Tc-99m activity

TcN-MPOTc-Sestamibi

A B

Journal of Nuclear Cardiology (2009) 16: 571-579.

Fast Liver Clearance and MDR

Journal of Nuclear Cardiology (2009) 16: 571-579.

99mTc-Teboroxime & Analogs

5 10 15 20 25

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99mTc-Teboroxime 99mTc-Teboroxime(F)

99mTc-Teboroxime(N3) 99mTc-Teboroxime(SCN)

Radio-HPLC Chromatograms for 99mTc-Teboroxime and Analogs

99mTc-Teboroxime & AnalogsT1/2 = 1.6 minT1/2 = 3.2 min

Comparison of 2-min Heart Uptake (%ID/g) for 99mTc

Radiotracers

99mTc-Teboroxime > 99mTc-Teboroxime(N3) ~ 99mTc-Sestamibi > 99mTcN-MPO

Gated SPECT with 99mTc-Teboroxime

SD rat injected with 14 mCi of 99mTc-Teboroxime

Image acquisition started at 0-30 min

(No Filter)

AcknowledgementAll postdoctoral fellows, visiting scholars and

graduate students over the last 10 years.