Myocardial perfusion agents
(Tl-201, Rb-82, Tc-99m agents)

POTASSIUM ANALOGS FOR MYOCARDIAL PERFUSION IMAGING

• Cs-127 and Cs-129 salts
   
• Rb-81 and Rb-82 salts
   
• Tl-199 and Tl-201 salts
   
• N-13 ammonium ion

 Why do Tl⁺, Cs⁺, and Rb⁺ behave like K⁺? These monovalent cations have an ionic radius, charge, and charge distribution very similar to that of K⁺. The heart is fooled by the similarity and there is uptake of these ions equivalent to that of K⁺.

POTASSIUM 43 AS A REFERENCE STANDARD

• K-43 was the first reference standard for cardiac imaging
   
• It is the physiological tracer and its uptake is flow-dependent
   
• 5-8% of injected dose localizes in the heart, which represents fraction of cardiac output passing through the coronary circulation
   
• Half life equals 22 hours
   
• Count rate peaks 10 minutes post-injection
   
• Difficult to collimate due to high energy- K-43 decays to Ca-43, emitting gamma rays having energies 0.369, 0.627, 0.219, 0.393, and 1.00 Mev
   
• Radiation dosimetry is a consideration since there are beta- particles emitted with energies of 1.839, 1.218, 0.927, 0.460, and 0.243 MeV with relative abundance of 1.6, 5.4, 83.1, 5.4, and 4.5 percent, respectively.

Rb-82 CHLORIDE FOR RAPID REPEAT STUDIES OF MYOCARDIAL PERFUSION

• Rb-82 has a short physical half life of 75 seconds and is useful for PET studies
   
• Tc-99m teboroxime (currently not available) has a short biological half life for both SPECT and planar imaging and repeated studies can be done during one day.

NITROGEN-13 LABELED AMMONIUM ION

• Positron emitter; t_1/2 equals 10 minute
   
• Extraction efficiency > than 90%
   
• Rapid blood clearance
   
• May be involved in enzymatic processes
   
• May involve Na⁺/K⁺ ATPase mechanism
   
• Marked lung uptake in all smokers
   
• Limited availability (requires cyclotron)- it is NOT commercially available
   
• Image quality similar to that of Tl-201

I-123 FATTY ACIDS

• Highly extractable compounds
   
• Metabolizable, especially in non-fasting state
   
• Ultimately produces carbon dioxide
   
• Images similar to Tl-201
   
• t _1/2 equals 13 hours; energy equals 159 keV
   
• Characteristic pattern in patients with ischemic cardiomyopathy
   
• Currently unavailable but easy to radiolabel

COST PER PATIENT STUDY (COMMERCIAL RADIOPHARMACY) JANUARY 2009

• Tl-201 chloride:  $15/mCi, $75 for stress/rest study
   
• Tc-heart agent:  $50-75/dose x 2 doses = $100-150 for stress/rest study

PHYSICAL PROPERTIES: Tl-201

• Low energy (71-80 keV X-rays from Hg-201 daughter)
   
• Potassium analog
   
• Perfusion marker under most conditions
   
• Redistributes
   
• Chemical form: Thallous Chloride (Tl-201)
   
• Tl-201 is a cyclotron produced nuclide with t _1/2 = 73 hours.
   
• Limitation: photons easily attenuated by body tissues (71 keV Hg x-rays)
   
• Long physical and biological half lives increase radiation dose, limiting patient injectable doses to 5 mCi
   
• Imaging procedure involves a stress exam followed by a second exam after redistribution which can take anywhere from 4-24 hours

PHYSICAL PROPERTIES: Tc-99m

• Low energy
   
• Tc-99m is a generator-produced nuclide with t _1/2 = 6 hours.
   
• Photons easily penetrate body tissues (140 keV g-rays)
   
• Relatively low radiation dose per mCi, so patient could receive a maximum of 40-50 mCi for a stress/rest study

PHARMACOLOGIC PROPERTIES OF THALLIUM-201

• Tl¹⁺ ion is a Potassium analog and is a perfusion marker under most conditions.
   
• Undergoes redistribution so stress-induced ischemias will fill in at rest.
   
• Imaging procedure typically involves a stress exam followed by a second exam after redistribution which can take anywhere from 4-72 hours

Tc-99m MYOCARDIAL PERFUSION IMAGING AGENTS

• Tc-Sestamibi has a long t_biol. Can image up to 6 hr post injection
   
• Tc-Tetrofosmin has a long t_biol. Can image up to 6 hr post injection
   
• Tc-Teboroxime has a short t_biol. Must image within 25 min time window post injection. Drug is currently off the market)

UTILITY OF Tc-99m SESTAMIBI: A MULTIPURPOSE RADIOPHARMACEUTICAL

• Myocardial perfusion imaging
   
• Parathyroid adenoma and breast tumor imaging
   
• Other tumor imaging

Tc-99m SESTAMIBI: PROPERTIES

• Labeled with Tc-99m
   
• Not a true potassium analog
   
• Uncouples from flow at high flow rates
   
• High extraction efficiency
   
• Long biological half-life
   
• Ease of preparation; stable for 6 hours

Tc-99m TETROFOSMIN: PROPERTIES

• Labeled with Tc-99m
   
• Not a true potassium analog
   
• Uncouples from flow at high flow rates
   
• High extraction efficiency
   
• Long biological half-life
   
• Ease of preparation; stable for 6 hours

Tc-99m TEBOROXIME: PROPERTIES

• Labeled with Tc-99m
   
• Not a true potassium analog
   
• High extraction efficiency
   
• Short biological half life
   
• Neutral and lipophilic (like xenon)
   
• Rapid myocardial clearance
   
• Ease of preparation; stable for 6 hours

Indications for Using Tc-99m Myocardial Perfusion Agents

• Identification of ischemic heart disease
   
• Detection and localization of myocardial infarction
   
• Assessment of global ventricular function and wall motion
   
• Perfusion, wall motion, and first pass studies
   
• Screening
   
• Emergency admissions
   
• Assessment of conventional therapies, thrombolytic therapy, and angioplasty
   
• Prognostic information
   
• Pharmacological stress testing

Key Advantages of Tc-99m Labeled Cardiac Agents

• Tc-99m Labeled Kit
   
• Available 24 hours a day
   
• Allows more scheduling flexibility
   
• Higher count rate = better images
   
• Ideal for SPECT imaging
   
• Measures perfusion and wall motion
   
• More diagnostic information from a single study
   
• Broader clinical applications

Comparison of Image Quality of Thallium 201 and Tc-99m Cardiac Agents

• Tc-99m has more optimal energy
   
• Higher injected dose means more photons and better counting statistics
   
• Higher target to background ratio
   
• More rapid acquisition
   
• Improved resolution
   
• Fixed Distribution provides flexibility and permits gating

Functional Imaging Using Tc-99m Cardiac Agents

• First Pass Ventriculography
   
• Ejection fraction
   
• Regional wall motion
   
• Gated Equilibrium Imaging
   
• Myocardial wall thickening
   
• Combined First Pass/Perfusion Study

Broader Clinical Applications of Tc-99m Cardiac Agents

• Acute Interventional Therapy, e.g., thrombolysis, angioplasty
   
• Cardiac Transplant
   
• Unstable Angina

Flexibility of Studies Using Tc-99m Cardiac Agents

• Multiple protocols on the same patient
   

  • Planar and SPECT

  • More than three views

  • Gated and static acquisition

  • First pass/Perfusion

§        Patient Scheduling

 Imaging time

Stress testing schedule

Same day/Two day protocols

Overview

§       Chronic CAD: Tc-perfusion agents equal to Thallium 201 for detection and vessel identification

§       Acute MI: accurate for detection and localization

§       Ventricular function: accurate for LVEF determination by first pass technique

§       Tc-99m is equivalent to TL-201 for detecting coronary artery disease