15 September 2016

Lecture #11: INFLAMMATORY PROCESS AND TUMOR IMAGING



GALLIUM IMAGING

Clinical indication

1.      Whole body survey to localize source of fever in patient with Fever of Unknown Origin.

2.      Diagnosing osteomyelitis and / or disk space infection. Ga – 67 is preferred over labeled leukocytes for disk space infection.

3.      Detection of pulmonary and mediastinal inflammation / infection especially in immunocompromised patients (AIDS, transplant patients).

4.      Evaluation and follow up of active lymphocytic or granulomatous inflammatory process such as sarcoidosis or tuberculosis

5.      Evaluation and follow up of drug induced pulmonary toxicity.

Clinical procedure

1.      2–10 mCi Ga–67 citrate is the typical dose administered.

2.      Imaging is performed 6–72 hours after.

a.      Earlier imaging times are favored for abscess detection.

b.      Later imaging is preferred for neoplastic disease.

3.      Ga–67 citrate has physical half–life of 78 hours with photopeaks at

a.      93 keV                  –          40%
b.      184 keV                –          24%
c.       296 keV                –          22%
d.     388 keV                –          7%

4.      The largest organ absorbed radiation dose (about 750 mrems/mCi) is the lower large intestine

5.      For whole body scintigraphy, anterior and posterior views are obtained at a rate of 6–8 cm/minute or 25–35 minutes or 1.5–2.5 million counts whichever comes first.

6.      For spot views, 250,000 to 1,000,000 counts should be obtained.

7.      Increase gallium biodistribution may result from blood transfusion, chemotherapy or iron therapy and recent trauma.

8.      Decreased gallium localization is seen in patients with gadolinium within 24 hours.

INDIUM–111 LEUKOCYTE IMAGING

Clinical indication

1.      To detect site of infection / inflammation in patients with granulocytosis and fever of unknown origin

2.      To localize an unknown source of sepsis and to detect additional sites of infection in patients with persistent or recurrent fever and a known infection site.

3.      To survey for sites of abscess or infection in a febrile post–op patients without localizing signs or symptoms.

4.      To detect sites and extent of inflammatory bowel disease.

5.      To detect osteomyelitis of different etiology.

6.      To detect mycotic aneurysm, vascular graft and shunt infection.

Radiopharmaceutical used

1.      Leukocytes are harvested from 40–80 ml venous blood for adult and 10–15 ml for pediatrics with granulocyte of 1–3 x 103 cells/ml in ACD or heparin anticoagulant. Leukocytes are labeled with In–111 oxine with methylene blue used as stabilizer.

Click here for full discussion on Blood Component Separation

2.      Radiolabeled leukocytes should be administered within 1–2 hours of cell labeling. Dextrose in water solutions should not be used, as these can cause clumping of labeled cells.

3.      70oF temperature increase cell damage thus should be avoided.

4.      Dosage for adult is 0.3 – 0.5 mCi while for pediatrics is 0.25 – 0.5 MBq/kg.

5.      In adults, the injected Tc99m sulfur colloid dose is in the range of 8–10 mCi and 20–25 mCi for MDP.

6.      Aspirin and antibiotics will exhibit lower labeling efficiencies.

7.      If platelets are tagged along with leukocytes, a false positive image may result because platelet concentrates in sites of thrombosis rather than areas of infection.

Acquisition parameters

1.      Imaging is performed at 4 and 24 hours after labeled leukocytes are administered to the patient. If the infection site is unknown, anterior and posterior views of the head, abdomen, pelvis and chest should be obtained.

2.      Indium–111 emits energy at 173 and 247 keV, both centered at 15–20% window.

3.      Whole body scan are acquired at a rate of 5–6 cm/minute which can last for 25 –35 minutes

4.      Tc99m sulfur colloid imaging is usually done after In–111 leukocyte imaging if there is question concerning bone marrow distribution.

5.      A normal image demonstrates tracer activity in the spleen, liver and bone marrow.

Other Indium–111 labeled radiopharmaceuticals

1.      Oncoscint

a.      5–6 mCi Indium–111 chloride is mixed with buffing solution

b.      The buffered solution is then added to the antibody

c.       The mixture is incubated for 30 minutes

d.     Since the antibody is a protein that can form particles, the preparation is filtered before intravenous administration

Oncoscint is a monoclonal antibody to the tumor antigen TAG–72 that is associated with ovarian and colorectal cancer. Because OncoScint is a human anti–murine antibody (HAMA), it has to be tested for allergic reaction. Imaging maybe performed as early as 2 days or as late as 5 days.

Click here for full discussion on Tumor Markers
Click here for full discussion on Hypersensitivity

2.      Octreoscan

a.      3.3 mCi Indium–111 chloride is mixed with pentetriotide and incubated for 30 minutes at 25oC.

Octreoscan is used in localizing metastatic tumors of neuroendocrine origin. This includes pituitary and endocrine tumors, paraganglioma, medullary thyroid carcinoma, carcinoids and small lung cancer. Octreoscan is an analog of octreotide, an analog hormone, somatostatin and bind on somatostatin receptor on surface of cells, concentrating in tumors with a high density for receptor sites.

Click here for full discussion on Somatostatin (Gastrointestinal Gland)

Tc99m–LEUKOCYTE IMAGING

Clinical indication

1.      To detect suspected sites of acute inflammation/infection in febrile patient with or without localizing signs and symptoms.

2.      To detect and determine the extent of inflammatory or ischemic bowel disease.

3.      To detect and follow up musculoskeletal infection such as septic arthritis and osteomyelitis

Radiopharmaceutical used

1.      Leukocytes are harvested from 20 – 40 ml venous blood for adult mixed with ACD anticoagulant with minimum granulocytes of 2 x 109 cells/liter.

2.      The usual dose for adult is 5–10 mCi

3.      Exametazime (HMPAO) is a lipophilic complex which penetrates the leukocyte cell membrane and is retained within the cells.

Acquisition parameters

1.      The pulse height analyzer is centered at 140 keV using a 15 – 20% window.

2.      Early imaging of the pelvis and abdomen is essential (bowel activity is seen in 20–30% of children by 1 hour and 2–6% of adults by 3–4 hours post– injection).

3.      Spot views should be at 800,000 counts/large field of view or 5–10 minutes.

4.      Images of limbs should be acquired for 10 minutes/view at 4 – 8 hours and at least 15 minutes/view at 16 – 24 hours.

BONE IMAGING

Indications

1.      Staging of malignant disease, screening of patients with primary tumors (e.g. breast, lung, prostate carcinoma) known to metastasize readily to bone, evaluation of response to therapy, localization of biopsy sites.

2.      Evaluation of primary bone neoplasms (e.g. Ewing’s sarcoma, osteogenic sarcoma); detection of sites in other bones; detection of soft tissue metastases.

3.      Diagnosis of skeletal inflammatory disease (e.g. osteomyelitis)

4.      Evaluation of skeletal pain of unknown cause

5.      Evaluation of elevated serum alkaline phosphatase level of unknown origin

6.      Determination of bone viability when blood supply to the area is in question

7.      Evaluation of painful joint prostheses

8.      Detection of occult fractures (e.g. sports injury) not demonstrated radiographically

Procedure of the test:

1.      Explain to the patient the reason for the delay between tracer administration and imaging.

2.      Administer 15–20 mCi Tc99m MDP intravenously. If a flow study is requested, position patient under the scintillation camera prior to tracer administration.

3.      Unless contraindicated, encourage the patient to drink four to six 8–oz glasses of liquid and to void frequently during the delay before imaging. Hydration of the patient helps clear the tracer from the body. Frequent voiding decreases the bladder’s exposure to radiation.

4.      Patient should void immediately before imaging. A large amount of radioactive urine in the bladder can obscure bony structures of the pelvis.

5.      Imaging can begin 3 hours after tracer administration.

6.      Ascertain patient has voided before proceeding with imaging.

7.      Use the spot image technique, whole body table technique or SPECT imaging technique to acquire data.

Image findings:

1.      Normal tracer distribution

a.      The radiopharmaceutical is normally taken up symmetrically throughout the skeleton. Areas of normally increased activity include sacroiliac joints, anterior iliac crests, sternum, nasopharyngeal area, shoulder joints and spine.

2.      Abnormal tracer distribution

a.      Abnormal tracer distribution can include areas of increased tracer accumulation within the skeleton itself or outside in soft tissue.

b.      Extraosseus activity is sometimes seen in the following sites: renal abnormalities, soft tissue inflammation, neoplastic masses, female breast, acute MI.

c.       Photopenic areas (areas of decreased tracer accumulation) are usually related to diminish blood flow to the area or to complete destruction or replacement of normal bone tissue.

Three phase / Four–phase Bone Imaging

1.      When an inflammatory process, such as osteomyelitis is suspected, dynamic or multiple phase bone imaging may be helpful to the physician in making a differential diagnosis.

2.      In this technique, the patient is first positioned under the gamma camera with the affected area in the field of view. The standard tracer dose is administered as a bolus injection while dynamic images are acquired beginning at the time of injection and continuing for about 1 minute.

3.      Immediate static images are then acquired, followed by delayed images at 2– 4 hours. The fourth phase consists of 24–hour delayed images.

4.      Both cellulitis and osteomyelitis demonstrate increased activity on the early images. With osteomyelitis, however, the tracer concentration persists throughout the delayed images.

Technical consideration:

1.      Extravasation of the tracer at the injection site may be construed as pathology or obscure bony pathology underlying the area of infiltration.

2.      There may appear to be overall decreased activity concentration in the bones if a significant amount of tracer is not administered intravenously. Imaging time may need to be extended in this instance to achieve adequate counting statistics.

3.      Since the tracer is excreted from the body throughout the urinary tract, radioactive urine contamination is possible with young children or older incontinent patients. Equipment should be protected and the patient should be checked for contaminated garments or linens before imaging begins.

4.      It is important that patients void immediately prior to imaging the pelvis. Excess activity in the bladder can obscure pelvic structures. Images of the pelvis should be obtained first, if the spot view technique is being used. Separate spot images of the pelvis may be necessary when whole body imaging is performed.

5.      Any attenuating materials such as jewelry, belt knuckles, removable prostheses, pocket contents or ECG leads, could cause a photopenic area on the image. Such materials should be removed from the patient prior to imaging.

6.      Contralateral sides of bony structures must be positioned at the same angle and at the same distance from the detector. Failure to do so may cause one side to appear to have a greater tracer concentration than the other. Asymmetry of contralateral sides may be falsely interpreted as an abnormality. It is equally important to include all areas of interest on the bone images a problem sometimes arises when certain parts of the skeleton, usually the arms, cannot be positioned within the field of view during whole body imaging.

7.      An unexpected pattern of tracer distribution may indicate improper preparation of the radiopharmaceutical and can degrade the quality of bone images. Excess free pertechnetate appears as tracer concentration in the thyroid, salivary glands and stomach. Liver uptake or increased soft tissue and kidney uptake can also be indicators of radiopharmaceutical problem.





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