Leucocytscintigraphy

Lene Rørdam Senior Consultant DMSci

Department of Clinical Physiology and Nuclear Medicine Bispebjerg University Hospital

Indications for leucocytscintigraphy in the past

• Inflammatory Bowel disease • Akut and chronic osteomyelitis • Failed joint replacements • Fever of unknown origin • Suspected antrabdominal absceses • Suspected prosthetic graft infection

Two different radioactive pharmaceuticals for in-vitro labeled white blood cells

Advantage Disadvantage 99mTc-HMPAO

Daily delivery Only labeling of the neutrophils (the other white cells dies). Plasma can be used as medium. Excelent imaging. Possibility for SPECT. Aquisition of imagies after 1-20 h. Low radiation dose (5.5mSv/500MBq)

Unspecific excreation to the intestines via the bile (can be seen in 2-6% after some hours and nearly alwayes the day after injection) Excreated via the urine.

111Indium Quantification of aktivity in the collected faeces over days. Possibility of imaging several days after injection . Dual isotope imaging.

Has to be delivered. Labeling of all white blood cells. Plasma can be not used as medium due to high affinity to platelets and and plasmaproteines. Low imaging quality. Only late images High radiation dose (11.8mSv/20MBq)

Illustration of image quality with the two different radiopharmaceuticals

In-vitro labeling of the white blood cells

• Demands special laboratory facilities • Not rutinely available • Involves contact with blood from a potential infected patient • Is time consuming (takes about 2½-3 hours) • Labeling enough leucocytes to produce usefull studies • Gentle handling of the blood to avoid activation of the leucocytes • Repeating imaging some times up to 24 hours after injection • In special cases supplementing with a marrow imaging

It is not an easy investgation

Is there still indication for leukocyte scintigraphy if you have acces to other imaging modalities e.g. 18FDG-PET/CT

Yes

But there are only few indications

Hip and knee arthroplasties • Denmark: • 8500 hip arthroplasties/year • 9000 knee arthroplasties/year

– 95% uncomplicated for > 10 years – 85% uncomplicated for > 15 years

– About 20% will get an aseptic loosening which often

leeds to a revision arthroplasty – 1%-2% will be infected (Revision arthroplasties 3%-10%)

• If infection is discovered less than 4 weeks after operation it can be saved othervise it has to be removed.

The failed joint replacement • The most common cause for prosthetic failore is aseptic loosening

(about 20% of the devices) – Results from an inflammatory reaction instigated by prosthetic components – The debris created by component breakdown activates and draws surrounding

leucocytes,(not neutrophils but monotcytes and macrophages) and trigger secreation of cytocines and enzymes damaging the osseus tissues leading to prosthetic loosening

Septic loosening occurs in up to 1-2% of primary implants and in about 5% of revision implants

Results in an inflammatory reaction characterized by a neutrophilic response, often intense.

It is extremely important for the surgean to know if there is infection because it demands a two stage operation instead of a single stage exchange arthroplasty

Palestro CJ: Nuclear medicine and the failed joint replacement: past, present and future. World J Radiol 2014; 6: 446-458.

Case 64 year old woman with a right knee prosthesis. Postoperative complicated by local infection. 8 months later there is increased infection parameters but no pain. Leucocytscintigraphy with 99mTc-HMPAO was performed

Posterior Anterior

The normal distribution of leucocytes are the liver, spleen and red bone marrow. In subjects with joint arthroplasty there can be seen red bone marrow in the periprosthetic bone. This can be confirmed by a bone marrow scintigraphy In this patient a bone marrow scintigraphy (99mTc-Nannocoll®) was performed 2 days later.

Posterior Anterior

Take home message

If you are in doubt Do always a bone marrow scintigraphy to reduce false positive results

Case 49 year old woman with a left hip arthroplasty 10 years ago. During the last months there were increasing pain in the left hip and femur. X-ray was supected for loosening of the femur component. There is increased CRP but normal leucocytes. A 18FFDG-PET scanning was performed

There was increased FDG uptake around the prosthesis and in the synovialis of the hip joint

Operation showed inflammation due to the polyethylene material. No infection

Case

80 year old woman had a right hip athroplasty 4 years ago.

Came to a 18FFDG-PET/CT scanning as a control 1 year

after operation for coloncancer.

Ultraguided puncture from the hip was positive for infection, wich was confirmed during operation.

Take home message

There is a high likelihood for infection in an arthroplasty if you find 18FFDG uptake in the periphrostetic soft tissues

Reinartz P et al. J Bone Joint Surg Br 2005; 87: 465-470

Case 71 year old man with a 2 year old revision arthroplasty in the right hip. He had pain on the lateral side of the femur and blood test showed increased CRP. X-ray without loosening. Ultrasound of the hip: i.a. A lucocytscintigrafphy was performed (99mTc-HMPAO), And later on a bone marrow scintigraphy was performed (99mTc-Nannocol®)

The patient did not want a removal of the prosthesis, so an exploration was performed. There were clinical infection around a cerclage around trochanter major distally for the joint, which was removed. Puncture from the hip was clinically without infection, but all peroperative biopsies were after cultivation positive with staphylococcus capitis and staphylococcus epidermidis. The patient is now on lifelong antibiotic treatment.

Case 81 year old woman with a left hip arthroplasty from 1999. Due to luxations she got a revision arthroplasty in 2003. Now there is increasing pain from the left hip and x-ray suspects loosening.

Leucocytscintigraphy with 99mTc-HMPAO was performed

3 hours postinj.

21 hours postinj.

Bone marrow scintigraphy.

Operation: Aseptic loosening due to debris from metal breakdown from the prosthesis. (Metal-to.metal hip arthroplasty)

Conclusion: Leucocytes are located in the red marrow.

Case

66 year old man with a left knee prosthesis 10 months ealier. It has never been perfect and there is now

increased pain and a swollen knee.

Leucocytscintigraphy with 99mTc-HMPAO was performed

Leucocytescintigraphy shows increased neutophile leucocytes around the prosthesis and in the syovialis of the knee joint. A bone marrow scintigraphy was performed after 6 days

Leucocyte scintigraphy

Bone marrow scintigraphy

There was no increase in neutrophile leucocytes accumulation from the early to the delayed images and the the red bone marrow showed the same distribution around the prosthesis, but there was synoviitis which gives suspecion of inflammation and not infection. Dermatological tests revealed allergy for neomycine (cross-allergy to gentamycine which is in the cement of the prosthesis) and puncture from the knee was negative for infection.

Take home message

Leucocyte scintigraphy images should be taken both early (3 hours) and late (20 hours). Increasing accumulation of neutrophile leucocytes indicate infection. If you are in doubt do a bone marrow scintigraphy

Case

68 year old man with a left hip arthroplasty. (It was a revision arthroplasty due to infection.) Now there is constant pain in the hip and x-ray suspects loosening of the femur and acetabulum.

Leucocytscintigraphy with 99mTc-HMPAO and a 18FFDG-PET scanning was performed

18FFDG-PET/CT

Case

There was clear signs of infection during the operation (Staphylococcus epidermidis). The arthroplasty was removed, and he was treated with antibiotics for 3 months. 6 month later a new prosthesis was inserted and he has been without symptoms now for 2 years.

49-year old woman had earlier an anterior cruciate ligament injury for which she was operated on several times. Got a right knee arthroplasty 1½ year ago.

Due to pain a bone scintigraphy was performed

Leucocytscintigraphy with 99mTc-HMPAO.

3 hours postinj.

21 hours postinj.

Bone marrow scintigraphy with 99mTc-Nanocoll®

Conclusion: Infection on the lateral side of femur. No signs of infection in tibia.

18FFDG-PET/CT

18FFDG-PET/CT

Operation results

• Clinical suspicion of infection on the lateral side of femur but biopsies were negative.

• Clinical no suspicion of infection in tibia and biopsies were negative.

66 year old man got a right hip hybrid arthroplasty after a hip fracture. 10 days after the operation he got a fracture of Trochanter major and the arthroplasty was replaced with a cemented arthroplasty. Since the operation there have been pain during walk. The patient has type 2 DM

Bone scintigraphy

hø

Leucocytscintigraphy with 99mTc-HMPAO

3 hours postinj.

22 hours postinj.

hø hø

18FFDG-PET/CT

Operation results • Totally loose femur arthroplasty

• Infection around trochanter major

• A large absces along the medial side of femur

starting 10 cm distal for trochanter minor.

• Was left with a Girdlestone status and got a revision arthroplasty 4 month later.

• Without symptoms after 3 years

Leucocytscintigraphy with 99mTc-HMPAO

3 hours postinj.

22 hours postinj.

hø hø

18FFDG-PET/CT

Conclusion

Elucidation of a failed joint replacement with radionuclide imaging: 1) Leucocytscintigraphy with early and late imaging. 2) If the results are difficult to interpretate:

Do a bone marrow scintigraphy

END