1. Frank P. Dawry

2. non-Hodgkin’s lymphoma
NHL is a cancer of B-lymphocytes.
There are 3 histologic grades of NHL: low-, medium-,and high-grade disease.
They differ with respect to their speed of progression, their patterns of response to chemotherapy, their patterns of relapse after chemotherapy, and the average patient life expectancy.
Frank P. Dawry

3. Immunotherapy
uses a monoclonal antibody designed to recognize and bind to a specific protein found on tumor cells.
bound antibody can inhibit tumor cells directly, causing apoptosis, so-called programmed cell death.
Antibody bound to tumor cells can also trigger the immune system to attack these cells, including activation of circulating complement and mobilization of killer lymphocytes
Frank P. Dawry

4. Frank P. Dawry

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6. Frank P. Dawry

7. Desirable to minimize damage to stem cells in the bone marrow
CD20 antigen is targeted
a transmembrane phosphoprotein that is expressed on pre-B-cells and mature B-lymphocytes but not on stem cells, lymphoid stem cells, plasma cells or nonhematologic normal tissues
Frank P. Dawry

8. Zevalin
Frank P. Dawry
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22. Frank P. Dawry

23. Radioimmunotherapy protocol
Bexxar (Tositumomab) anti-B1 murine monoclonal antibody that binds to the CD20 antigen.
Radioimmunotherapy protocol
Consists of the administration of a combination of unlabeled antibody and antibody labeled with 131I.
A saturated solution of potassium iodide is given from the day before the dose through 14 d after the therapy dose.
Patients initially receive a 450-mg infusion of unlabeled tositumomab (predose) over the course of 1 h, followed by a 20-min infusion of 35 mg 131I-tositumomab and a 10-min saline flush.
Frank P. Dawry

24. THERAPEUTIC DOSE DETERMINATION
Start by administering a small initial dosimetric dose to measure each patient’s individual biologic clearance.
This allows the therapeutic dose to be tailored to the clearance rate so that the desired radiation absorbed dose will be delivered.
Frank P. Dawry

25. Images obtained as part of dosimetric study to determine the patient specific dose
Frank P. Dawry

26. Dosimetric study to determine the patient specific dose
The residence time and a parameter called “activity hours” are used to calculate the amount of 131I activity necessary to administer the required radiation absorbed dose.
The background corrected patient counts are used to model an exponential clearance rate for the radiolabeled tositumomab and derive an estimate of the residence time
The activity hours parameter is obtained from a table (generated by the manufacturer from pooled pharmacokinetic data and MIRD dosimetry calculations) and is based on the patient’s height and weight.
Frank P. Dawry

27. THERAPEUTIC DOSE DETERMINATION
differing biologic clearances of the radiolabeled antibody will change the total radiation absorbed dose to the patient and to the tumor for a given amount of administered activity.
To deliver the maximum suggested total body dose of 75 cGy, patients with fast biologic clearances would require a high administered dose and those with slow clearance would require a low administered dose
Frank P. Dawry

28. Frank P. Dawry

29. TOSITUMOMAB ADMINISTRATION
The initial unlabeled (cold) antibody dose may be administered in the hematology department
450-mg tositumomab dose is administered in a 50-mL volume of saline over the course of 1 hour
An indwelling catheter should be used for the infusion to avoid extravasation.
Butterflies should not be used.
The infusion is given through a 0.22-m filter.
The infusion rate should be slowed or the infusion should be temporarily stopped if the patient develops fever, rigors, mucosal edema, or hypotension.
Serious reactions such as anaphylaxis are unlikely, but support equipment should be available.
Frank P. Dawry

30. Radiolabeled TOSITUMOMAB ADMINISTRATION
The 131I-tositumomab (35 mg) infusion is given shortly after the unlabeled antibody infusion.
This dose must be administered in a controlled radiation area, usually the nuclear medicine department.
The dose is given in a volume of 30 mL over 20 min and is followed by a 30-mL saline flush over 10 min.
The venous catheter that was used for the unlabeled antibody infusion may be used for this infusion.
A 0.22-m filter is again used.
Therapeutic doses of tositumomab are typically around 3,330 MBq (90 mCi) 131I and may be as high as 5,550 MBq (150 mCi).
Because the 131I is bound to the antibody, volatilization of the 131I is not an immediate problem
Frank P. Dawry

31. PATIENT RELEASE CRITERIA Can patients administered high activities of I-131 go home?
Original Nuclear Regulatory Commission (NRC) release criteria:
a body burden of 1,110 MBq (30 mCi) or,
measured dose rate at 1 m ≤ 0.05 mGy/h (5 mrad/h).
1997 NRC rule, 10 CFR 35.75, allowed the use of patient-specific calculations.
These calculations are based on the principle that individuals exposed to the patient receive no more than 5 mSv (500 mrem).
Regulatory Guide 8.39: Release of Patients Administered Radioactive Materials
Frank P. Dawry

32. PATIENT RELEASE CRITERIA (Continued)
To comply with these regulations, several requirements must be fulfilled.
The institution must maintain records of the basis for releasing the patient.
These must include
an interview with the patient to determine potential exposure to others,
dose rate measurements if dose rate criteria are used,
and a copy of the written instructions that must be given to the patient.
Frank P. Dawry

33. Applying Nuclear Regulatory Commission Guidelines to the Release of Patients Treated with Sodium Iodine-131 William K. Tuttle, III and Paul H. Brown Imaging Service, VA Medical Center and Department of Diagnostic Radiology, Oregon Health Sciences University, Portland, Oregon
Frank P. Dawry

34. Applying Nuclear Regulatory Commission Guidelines to the Release of Patients Treated with Sodium Iodine-131 William K. Tuttle, III and Paul H. Brown Imaging Service, VA Medical Center and Department of Diagnostic Radiology, Oregon Health Sciences University, Portland, Oregon
Frank P. Dawry

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36. Bexxar vs. Zevalin
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Frank P. Dawry