Radiopharmaceuticals in Nuclear Cardiology

1. When compared to ²⁰¹Tl think about the following
1. T1/2
2. Energy
3. Redistribution
4. Attenuation
5. Wall motion
6. Thrombolytic therapy - article
   1. What are the risks to this approach?
   2. How quickly does the heart tissue become necrotic after arterial occlusion?
7. Extraction Fraction
2. Pathophysiology of sestamibi (methoxy isobutyl isonitrile)
1. Lipophilic monovalent cation
2. Sestamibi adheres to the mitochondria via a negative transmembrane potential
3. Sestamibi will only go to viable myocardial tissue via an adequate blood supply
4. Two critical factors for uptake is
   1. Flow flow
   2. Viable myocardial tissue that contains mitochondria
5. Further details link to this Article - "Technetium (99mTc) Sestamibi"
6. Extraction fraction is less than ²⁰¹Tl
7. May overestimate myocardial scarring at high flow rates, which occurs during pharmacological stress test (can you explain why?)
8. This agent undergoes minimal redistribution, about 20% within 20 to 60 minutes post dose
1. Result may underestimate an ischemic defect, do to this redistribution (can you explain why?)
2. To minimize the redistribution effect imaging should be started within 15 minutes post stress injection and the rest dose within 60 minutes post injection (why would you have to wait 60 minutes post rest before imaging?)


http://www.wjnm.org/article.asp?issn=1450-1147;year=2013;volume=12;issue=1;spage=8;epage=13;aulast=Al-Shammari

9. Hepatic and bowel uptake (whole body distribution of sestamibi is seen above)
1. Primary route of excretion is 33% from the hepatics (T1/2 = 30 minutes)
2. Left lobe and gall bladder may interfere with imaging/processing
3. Small bowel uptake may interfere with imaging/processing
4. Furthermore, interference my draw counts away from the myocardium
5. Following an MPI procedure a lung scan is completed on the patient 24 hrs later. Besides lung uptake, what else would you expect to see on a VQ scan?


http://www.saudija.org/article.asp?issn=1658-354X;year=2011;volume=5;issue=3;spage=342;epage=344;aulast=Fathala

6. High hepatic uptake may cause inferior wall defect(s) as seen above - like the image to enlarge
7. Renal excretion = 25%
8. Target organ is the upper large intestine
10. Sensitivity = 90% and specificity = 80%
11. Imaging and processing will be discussed later

1. Many similarities to sestamibi, with some differences. In the end, doe it really matter whether you image with tetrofosmin or sestamibi?
2. Is lipophilic, cation, diphosphine that has rapid cardiac uptake (1,2-bis[bis(2-ethoxyethyl)phosphinpo])
3. Does not significantly redistribute
4. Differences between tetrofosmin and sestamibi, consider
   1. Hepatic clearance as it relates to target and background
   2. Extraction fractions
5. In the end, what does this all mean?
   1. Following the resting injection tetrofosmin can be imaged sooner
   2. During stress, if the patient reaches 85% stress on a treadmill imaging can occur as soon as the heart returns to a resting state, which either technetium agent
   3. When using a pharmacological agent imaging it may not matter which technetium agent you use, it takes a while before the background clears
   4. Gremillet E, et al indicate that sestamibi has higher count rate. This may be due to its greater extraction fraction
   5. Ravizzini et al while there may be little difference between the technetium agents tetrofosmin has greater patient throughput and less repeat procedures
   6. In the end Kapur, A. et al. compared over 2000 patients with all three radiotracers and concluded
      
      1. The technetium agents had better imaging quality with greater counts and reduced attenuation artifacts
      2. However, all three agents scored well with sensitivity and specificity when compared with cardiac angiograms

Comparison of the Agents - According to the manufacturer

1. Extraction fraction
1. In canine
1. ²⁰¹Tl = 82 to 88%
2. Sestamibi = 68.3% +/-4.7%
3. Tetrofosmin = 54.0% +/-3.7%
2. Redistribution
1. ²⁰¹Tl = Redistributes
2. Sestamibi = Insignificant
3. Tetrofosmin = Insignificant
2. Decreased myocardial extraction is seen with all cardiac agents - as flow rate increases, radiotracer extraction decreases. This is true of all the radiopharmaceuticals: ²⁰¹Tl , Sestamibi, Tetrofosmin. Refer to the chart

3. Myocardial uptake of sestamibi and tetrofosmin at 5 minutes and 60 minutes post injection

1. At rest and tetrofosmin has slightly better count density, whereas at stress sestamibi seems higher
2. Tetrofosmin clearance was faster from lungs and liver
3. Myocardial uptake in planar imaging
1. (Normal patients) At rest sestamibi and tetrofosmin had similar results
2. (Normal patients) At stress tetrofosmin counts per pixel was higher at 5 and 60 minutes post injection, when compared with sestamibi
3. (Patients with CAD) Tetrofosmin uptake as greater than sestamibi
4. Heart to liver and Heart to lung ratios are similar - Indicates tetrofosmin can be imaged sooner
1. Sestamibi requires 60 minute post injection
2. Tetrofosmin requires 30 minutes post injection
3. Hence, the advantage to using tetrofosmin is reducing the patient's waiting time (from injection to being imaged). This should allow for an increase the amount of cardiac scans a clinic can do on a daily bases.
4. The argument against tetrofosmin is that it has a reduced extraction fraction when compared to sestamibi. Would a reduced extraction fraction effect the diagnostic capability of the radiopharmaceutical?
5. According to the package insert, "the actual metabolism (pathophysiology) has not been established