Yttrium-90 Bremsstrahlung Imaging

Yttrium-90 imaging is probably not the first thing that comes to mind when scanning in Nuclear Medicine as an isotope, namely because it is outside of the realm of our usual Technetium-99m based radiopharmaceuticals. I have written about Y-90 and Theraspheres in the past blogs (parts I and II), but this time instead of discussing the treatment aspect, we will look at the imaging aspect of using Y-90 and its Bremmsstrahlung x-rays that it produces.

Imaging was performed on a patient who was diagnosed with hepatocellular carcinoma.  Early in the treatment planning with computed tomography (CT) and interventional arteriography, a large mass was localized in segment 4A/B in the liver.   Majority of the vascularity was provided by the left hepatic artery.  The middle hepatic artery and gastroduodenal arteries were then coiled embolized to limit perfusion.  This patient was on the third treatment cycle of Y-90 Therasphere.  The growth of the liver lesion was stabilized with the first two treatments but there were some suspicions of new metastases.

Fig. 1  Finding the common hepatic artery during the arteriogram.  Quite honestly, I can not figure how the interventional radiologists navigate through the arteries like that... There are no google maps for this!

Fig. 2  The right hepatic artery.  Notice the blush within the lesion as the contrast was infused.  I find this quite amazing to see in person.  In the end the interventional radiologists decide to use the left hepatic artery to infuse the Tc-99m MAA to determine the lung shunt fraction and in turn was used to infuse the Y-90. 

What we wanted to accomplish was to ensure that the Y-90 Theraspheres that we were infusing had truly localized within the liver segments that we wanted to treat.  In the past we had indirectly measured the activity using a dose rate meter (Bicron - mSv/hr) to examine the exposure rates to various parts of the chest and abdomen after the infusion.  The tricky part of the whole thing was that we had never scanned Bremmsstrahlung x-rays before.

Luckily there is an array of information on the internet, but the problem is trying to decipher all this information.  The Y-90 Bremsstrahlung spectrum looks very different, when low energy all purpose (LEAP), medium energy (ME) and high energy (HE) collimators are fitted onto the gamma camera.

Fig. 3  Top:  Represents the Bremsstrahlung spectra on a gamma camera without collimation.  Second:  Represents the spectra with a low energy all purpose (LEAP) collimator.  Third:  The spectra with a medium energy (ME) collimator.  Bottom:  The spectra with a high energy (HE) collimator.  Note 1:  If anyone who is reading this - can someone confirm what the lower peak is?  (It's a scatter peak of some sort - it may be a dumb question, but I need to ask it for my knowledge).  Note 2:  Diagram was taken from:  Planar Gamma Camera Imaging and Quantitation of Yttrium-90 Bremsstrahlung

Fig. 4  There is a characteristic x-ray photopeak between 75 - 79 keV with collimation.  This is the range where we decide to use our window for imaging.  However, note on the far right in Fig. 3 TOP, and in Fig. 4 another interesting peak occurs on around 180 - 210 keV.  This is probably the result of septal penetration due to some high energy Bremsstrahlung x-rays.

Furthermore, where do we centre the energy window and how big should the window be?  There is a characteristic x-ray peak, as indicated above, around 75 keV.  But what is interesting is that some protocols use a 79 keV peak with a 26% window, while others use a 90 keV peak and a window width of 15%. So what is the optimal imaging parameter in regards to the energy peak and energy window?  I am not really sure, and I think it really has to do with the testing that we need to do on our camera system (Seimens Symbia T-6) to figure this out in terms of sensitivity, resolution and target to background ratios.  However we did not have the luxury of time to test these parameters.  When we first started the trial, it was never our intention to image the Y-90 Therasphere patients, and this patient was a "one off".

However there is some agreement with respect to the collimation.  From what I have read between ME and HE collimators, generally speaking, most have used the ME's.  In our case, the administered dose was approximately 2.03 GBq and imaging was performed 3 days later, we opted for the ME's since there were not going to be any significant differences between sensitivity and resolution between ME and HE collimators for equivalent energy windows (ie. whether we were using a 26% or 15% window).  

So these are our results:

Fig. 5 Coronal fused section from the SPECT/CT (Symbia T-6) with localization in the segment 4 of the liver

Fig. 6  Sagittal fused section from the SPECT/CT (Symbia T-6)

Fig. 7  Transaxial fused section from the SPECT/CT (Symbia T-6)

The MIP after reconstruction looks like a "big blob".  It didn't look too bad with regards to the planar images which we also obtained.  We had captured them to quickly examine the target lesion to background liver fraction.

Fig. 8  Anterior image.  We imaged for 600 secs and obtained approximately 700K to 1700K total counts (posterior/anterior images respectively)

Fig. 9  A quick target lesion to liver background ratio was calculated to determine the amount that remained in the liver 3 days after the infusion

In the end we decided to use the MD Anderson's protocol.  It was a shot:

NM Planar & SPECT Y-90 Bremsstrahlung Imaging:

– 79keV/26% window, MELP collimation, 128x128 matrix, 4.8 mm2 pixels, 128 

views/360°, 28 s/view, non-circular step-shoot

So we did all this, BUT some might say... what about imaging the patient on the PET/CT unit? Well I wish we could, as you know, Y-90 is a beta emitter and this is certainly within the realm of possibilities, and with it, a huge array of literature on this as well.  We thought about it, but we couldn't get imaging time on the PET/CT unit... so we opted for regular gamma camera imaging.  QED.

Liver Spleen Scan Using Denatured Red Blood Cells

Denatured red blood cell scans are few and far between, but when something like this comes along, it piques everyone's interest. 

With this case here, the ordering physician was inquiring about the multiple intra abdominal deposits and had asked whether these deposits were related to splenules, caused by some kind of splenosis.  We are uncertain about the patient history since the technologist performing the scan did not inquire about the previous history of trauma or any iatrogenic events that may have potentially caused the spleen to rupture.  Previous ultrasounds or CT imaging were not performed at our facility and the patient did not bring any CD's with previous imaging from outside sources.  But thinking back, this patient must have some form of imaging done or otherwise, how did the physician know of the abdominal deposits?  At any rate this is what we got with respect to the imaging.  

After the initial reinjection of the denatured cells, a flow and blood pool images were acquired.  The delayed imaging was performed 20 minutes post injection, using a 2 bed SPECT/CT protocol.

Fig. 1 Anterior blood pool, after the denatured red blood cell injection.

Fig. 2 Posterior blood pool acquisition.

Fig. 3  Coronal slice.  Multiple foci of activity.  Note the activity over the dome of the liver and the perihepatic regions.

Fig. 4  Multiple uptake within the peritoneal cavity.

The MIP display above might not seem like very much, but there are multiple foci of tracer uptake scattered throughout the peritoneal cavity and the perihepatic region.  The largest and the most intense nodules occur in the splenic fossa along with multiple nodules tracking along the colon.

Fig. 5  SPECT/CT acquisition was performed to localize the denatured red blood cell uptake.

There is also focal activity in nodules adjacent to the liver as well as further nodules in the lateral right hepatic border and in the hepatorenal space.  Overall a lot of diffuse uptake can be observed, which is highly suggestive of splenosis.

We have a GMP approved radiopharmacy and all of the blood work is performed on site.  I must admit in the past, sometimes the labeling worked and sometimes it did not, however we have tweaked the procedure a little bit, and the information below is how we label and denature our red blood cells to ensure a quality scan.

Preparation of Radiolabeled Red Blood Cells Using the UltraTag In Vitro Method:

      Purpose:

The aim of this document is to provide information on the preparation and quality control of ^99mTc-labeled red blood cells using the UltraTag® in vitro method.

     Responsibilities:

It is the responsibility of the radiopharmacy technician to perform this procedure under strict aseptic conditions and as outlined in this protocol.

It is the responsibility of the radiopharmacist or the quality control technician to ensure that the correct RBC preparation procedure is followed and the final product meets the required specifications.

    Materials:

- lead glass syringe holder (3 mL size)

- syringe lead pig

- vial lead pig

- sterile 15 mL plastic centrifuge tubes

- sterile 18 or  21 gauge needles

- sterile 5 mL and 3 mL syringes

- sterile saline 0.9 % for injection USP

- UltraTag® kit

- ^99mTc sodium pertechnetate (370 – 1000 MBq)

    Procedure:

4.1.  Area setup:

·       Turn on laminar flow hood and wipe down surface of the hood with 70% isopropyl alcohol and a clean Kendall wipe. Spray and wipe with 70% IPA the materials needed to be placed in the hood.

·       Don hair cover, face mask, gloves and gown.

·       Turn on water bath and set the temperature at 50^oC, if preparing denatured RBC.

4.2.  Precautions:

·       During the labeling procedure, blood and blood components of the patient, who could potentially be infected with pathogens, need to be handled. To prevent contamination of the operator, double-gloving using waterproof gloves is recommended.

·       Since the cells have to be reinjected into the patient, strict aseptic conditions are required for the labeling procedure.

·       Simultaneous labeling of blood products from multiple patients is discouraged in order to prevent possible cross-contamination. At all times correct identification of the patient’s blood products should be guaranteed.

·       During the labeling care should be taken not to damage the cells, as this would result in leakage of the radioactivity from the cells, increased lung uptake and increased liver uptake.

4.3.  Radiolabeling of RBC with ^99mTc:

Note: The UltraTag® kit has 3 components:

a)     10 mL reaction vial containing stannous chloride, dihydrate (SnCl2•2H2O) 50 µg, minimum, stannous chloride, dihydrate (SnCl2•2H2O) 96 µg, theoretical, tin chloride (stannous, stannic) dihydrate, as stannous chloride, maximum dihydrate 105 µg, 3.67 mg sodium citrate dihydrate and 5.50 mg anhydrous dextrose.

b)     Syringe I: 0.6 mL contains 0.6 mg sodium hypochlorite (NaOCl). Protect from light.

c)   Syringe II: 1 mL contains 8.7 mg citric acid monohydrate, 32.5 mg sodium citrate dihydrate and 12.0 mg anhydrous dextrose.

4.3.1.     Collect patient's blood sample (1 - 3 mL) using heparin or ACD as an anticoagulant. The amount of ACD should not exceed 0.15 mL of ACD per mL of blood. The recommended amount of heparin is 10-15 units per mL of blood. DO NOT USE EDTA OR OXALATE AS AN ANTICOAGULANT.

4.3.2.     Using a large-bore needle (19 to 21 gauge), transfer 1.0 to 3.0 mL of anticoagulated whole blood to the reaction vial and gently mix to dissolve the lyophilized material. Allow to react for 5 min at room temperature.

4.3.3.     Add contents of Syringe I, mix by gently inverting four to five times.

4.3.4.     Add the contents of Syringe II to the reaction vial. Mix by gently inverting four to five times.

4.3.5.     Place the vial in a lead shield fitted with a lead cap. Add 370 to 925 MBq (10 to 25 mCi) sodium pertechnetate Tc-99m (in a volume of up to 3 mL) to the reaction vial. Use fresh generator eluate to avoid in-growth of ⁹⁹Tc.

4.3.6.     Mix by gently inverting reaction vial four to five times. Allow to react for 20 minutes with occasional mixing.

4.3.7.     Take a sample to assay labeling efficiency immediately prior to injection (see 4.4.2).

If LE > 90%, proceed to step 4.3.8 for denatured RBC or step 4.3.9. for normal RBC.

4.3.8.     Heat the tagged cells in a water bath with a little agitation at 49 - 50^oC for no more than 15 min. Proceed to step 4.3.9.

4.3.9.     Mix gently prior to withdrawal of patient dose. Aseptically transfer the ^99mTc-labeled red blood cells to a syringe for administration to the patient. Use a large bore needle to prevent hemolysis.

4.3.10.  Assay for radioactivity. Prepare labels and paper work using Pinestar.

4.3.11.  ^99mTc-labeled red blood cells should be injected within 30 minutes of preparation or as soon as possible thereafter.

4.3.12.  Clean up the laminar flow hood. Place radioactive waste in the waste disposal bin in the hot lab and non-radioactive sharps waste and blood/plasma in the sharps waste container. Remove the equipment from the laminar flow hood and wipe the surface down with 70% isopropyl alcohol using a lint-free cloth.

4.4. Quality control:

4.4.1.     Visual inspection (performed routinely):

·         At the end of the procedure and before collecting the radiolabeled RBC in the syringe for patient administration, a visual inspection for clumps, clots and aggregates should be performed by gently rotating the tube.

·         In case of aggregates, they should be dissolved by gently shaking or pipetting the sample.

·         If clumps cannot be dissolved, the preparation should not be injected.

4.4.2.     Labeling efficiency (LE) (performed routinely):

·       Transfer 0.2 mL of the ^99mTc-labeled RBC to a 15 mL centrifuge tube containing 2 mL of 0.9% NaCl. Centrifuge for five minutes and carefully pipet off the diluted plasma. Measure the radioactivity in the plasma and red blood cells separately in a dose calibrator. Calculate labeling efficiency as follows:

% LE = (Activity RBC x 100)/(Activity RBC + Activity Plasma)

·         LE = 90 - 98 %

·         If LE < 90 %, further quality control should be performed, such as microscopic inspection and test for cell viability (see 4.4.3).

4.4.3.     Trypan blue exclusion test for cell viability (recommended periodically):

·       Take a small sample (0.2 mL) from the radiolabeled RBC and dilute it with 1 ml of saline for injection.

·         In a small tube mix 50 ul 0.4 % trypan blue solution and 50 ul of the radiolabeled RBC sample.

·         Put a drop of this mixture in a hemocytometer and place it under the microscope.

·         Check for clumps and microaggregates of cells.

·         Calculate the percentage of blue stained cells from the total cell number. This is the percentage of damaged cells.

·         If a preparation has > 10 % blue-stained cells, it should not be released for injection into the patient.

4.4.4.     Sterility (recommended periodically):

Sterility of the final preparation should be tested periodically, especially in case of any modification to the procedure.

So there you have it.

NB:  Someone had mentioned that I forgot to add steps 5.3.8, 5.4.2, 5.4.3. Everything is contained within the blog.  I just mislabeled the numbered steps.  The "5" should have been a "4" in the body of the blog.  Apologies, it has been corrected..