The physics of Nuclear Imaging part 1

Outlines:

1-Radiopharmaceuticals

2-Radiopharmaceutical QC

3-Dose Calibrator QC


 

1-Radiopharmaceuticals:

·       Definition: Radiopharmaceuticals consist of a radioactive isotope, which creates the image, and a pharmaceutical, which determines the physiological behavior of the compound and, therefore, where the signal accumulates to form the image.

·       Properties of ideal radiopharmaceuticals:

1.     Easily and firmly attached to the pharmaceutical at room temperature but has no effect on its metabolism.

2.     Readily available at the hospital site.

3.     A high-specific activity

4.     High target: non-target uptake ratio

5.     Easy and cheap to produce

6.     Non-toxic

7.     Does not alter physiology in order to give an accurate depiction of the patient’s physiology

8.     The effective half-life should be similar to the exam duration to reduce the patient dose

9.     Pure gamma emitter for imaging and pure particle radiation emitter for therapy

10.  Easily to be eliminated from the body

·       Examples:

1.     99mTC-MDP (bone scan): MDP works as a pharmaceutical to be bonded to a 99mTc radioisotope. 99mTC-MDP is accumulated at the highly active areas where osteoblasts use the phosphate group to build the broken bone or repair the inflammatory sites because of metastis occurance.

2- 99mTc-MIBI (cardiac scan): MIBI works as a pharmaceutical, while 99mTc as a radionuclide, 99mTc-MIBI is going through the patient’s blood to reach the mitochondria to form electrostatic binding (+ve 99mTC-MIBI and -ve mitochondrial surface). that’s why you will find 99mTC -MIBI in the organs containing mitochondria i.e heart, liver, and muscles ….

o   The myocardial wall defects and cardiac functions are diagnosed by 99mTc-MIBI

o   the coronary arteries blockage prevents the passing of 99mTc-MIBI to the myocardial wall.

o   the stenosis or the occlusion of coronary arteries reduces the blood flow to a certain segment of the left ventricle, so this segment contains less amount of radioactive material which is shown as a cold or hypoactive region in the image.





 

 

 

 

 

 

 


2-Quality control procedures in the hot lab:

       Generator (Alumina, Moly breakthrough, pH)

       Radiopharmaceutical (TLC labeling efficiency test)

     Dose Calibrator


       Generator (Alumina, Moly breakthrough, pH) :

1-Alumina breakthrough test

We have to assure that alumina concentration doesn’t exceed 10PPM in the eluate.

Materials:

o   Alumina standard solution

o   Two Filter papers (A and B)

 

Procedure by colorimetric method :

o   put a drop of alumina standard solution on the filter paper (A) and monitor the color of the drop.

o   put a drop of the eluate (free 99mTc) on another filter paper (B)

o   compare the intensities of color between A and B.

o   if the color intensity of B is less than A, so it is an accepted result.



2-Mo-99 breakthrough test

o   We have to assure that Mo-99 activity doesn’t exceed 0.15 uci per 1 mci of 99mTc at the time of administration.

 

Material:

o   Lead shield or canister for Mo-99

o   Dose Activity meter



Procedure:

o   Put the eluate in the activity meter and record the reading A by pressing the 99mTc button

o   Put the eluate in the lead shield.

o   Put the shield containing the eluate in the activity meter and record the reading B by pressing the Mo-99 button.

o   The moly activity is calculated by the equation 1-((A-B)/A))

·       Radiopharmaceutical (TLC labeling efficiency test) :

o   To assure the labeling efficiency of 99mTc with pharmaceutics.

o   The free technetium 99mTc is able to bind with the pharmaceutics under certain conditions.

o    The suitable condition of radiopharmaceutical preparation varies with different types.

o   The preparation may require:

o                                 PH of the solution, how much activity is required? , heating condition (Temp, heating time ), how much volume is required?

o   Any change in the suitable parameter cause reduction in the labeling efficiency of radiopharmaceutical which disrupts the biodistribution.

o   There are three product results after preparation: the free technetium 99mTc, the hydrolyzed reduced technetium, and the labeled radiopharmaceutical.

o   Our target is to reach the labeling efficiency of radiopharmaceuticals greater than > 90 %.

o    Thin Layer chromatography (TLC) is used to discriminate between the three types of preparation products.

o   TLC permit to each product to pass through it to reach a certain distance. we are using a solvent which able to reach the maximum distance (solvent front) of TLC paper.

o   The ratio between the distance traveled by the (product + solvent) to which traveled by the solvent only is called the Rf value.

o   Each product bound to a solvent has an Rf value. If Rf =1, the (product + solvent) reaches the same distance traveled by the solvent alone.

o   The solvent type varies from one radiopharmaceutical to another.

§  Procedure:

o   Prepare the radiopharmaceutical solution

o   Put a drop of the solution at the origin line of the TLC paper and let it dry.

o   Immerse the TLC paper vertically in a specific solvent, but make the solvent surface below the origin line of the TLC paper.

o   Wait for a few minutes, to let the solvent pass through the TLC paper taking the product to a certain distance.

o   Based on the Rf values, each product will reach a certain distance.

o   Then, we cut the TLC paper to different segments. each segment contains a certain product of the radiopharmaceutical solution.

o   Each segment should be measured by dose activity meter to record the dose for each segment.

o   We can calculate the labeling efficiency, by measuring the dose of labeled product and dividing the result by the total dose of all segments.

o   The result should be multiplied by 100 to get the labeling efficiency in percent 



o   Dose Calibrator:




Required Dose Calibrator Tests and Frequency of Performance
Test for Accuracy
This test is intended to demonstrate that the calibrator is providing accurate readings across the whole energy scale that is expected to be encountered. The dosage calibrator measures low, medium, and high energy standards (often Co57, Ba133 or Cs137, and Co60) using appropriate settings. The label value showing activity at a certain calibration time and date is mathematically decay-corrected to the testing date. The standard is then tested in the dosage calibrator, and the measured and standard values are compared. All values are entered in the corresponding logbook. The measured values must be within 10% of the standard value. The data acquired during an annual Accuracy Test is shown in the table below. The dose calibrator was found to be accurate.



o   Constancy Test
o   This test, performed at installation and on a daily basis, examines instrument precision and is intended to demonstrate that reproducible readings are produced day after day on all isotope settings that are likely to be utilized. In the dosage calibrator, a long-lived source, typically 30 yr Cs-137, is used. The activity is then measured on the Cs-137 setting (which actually represents a "mini" accuracy test) as well as all other daily settings. readings are entered in the proper logbook and compared to recent readings to assess if the instrument is consistently performing on a daily basis. Values measured must be within 10% of the standard value. It should be mentioned that, because we are reading the activity of a Cs137source on Tc99m and Tl201 settings,It should be emphasized that because we are reading the activity of a Cs137source on settings for Tc99m, Tl201, I123, Xe133, and other isotopes, we will acquire inaccurate values. We anticipate getting the same inaccurate reading day after day. The data acquired during a daily constancy test during a one-week period are shown in the table below. The dose calibrator was found to be accurate.




Linearity Test 
This test is intended to demonstrate that the dosage calibrator readout is linear for sources ranging from Ci to mCi. At T0 and at predefined time intervals, a high activity Tc99m source (50-300 mCi) is detected until activity reaches around 30 Ci. Depending on the initial activity, this can take up to 96 hours. The activity at T0 can be decay-corrected using Tc99m decay factors to forecast what the activity should be at the predetermined times. Expected and actual data are recorded in the appropriate logbook (and may be analysed graphically), and then compared to evaluate if the instrument is linear across the dosage calibrator's useful activity range. The data is shown in the table below.

 

 

 

   Geometry Test
This test is intended to demonstrate that accurate readings can be produced regardless of sample size or geometry. As a result, this test must be performed on each different bottle used (e.g., 10 ml, 30 ml) as well as each different syringe used (e.g., 1 ml, 3 ml, 5 ml, 10 ml). To test the linearity of a 10 ml syringe, for example, first place 1.0 ml of Tc99m (activity 25 mCi) in the syringe. The activity is then measured in the dosage calibrator, and the resulting value is saved. The activity is then diluted with water in increments of 2.0 mL, 3.0 mL, 4.0 mL, 5.0 mL, and so on, up to 10 mL. A reading is obtained at each of these places, and the value is calculated.







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