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A Primer for Radioimmunotherapy and Radionuclide Therapy

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A Primer for Radioimmunotherapy and Radionuclide Therapy AAPM REPORT NO. 71 A PRIMER FOR RADIOIMMUNOTHERAPY AND RADIONUCLIDE THERAPY Report of Task Group #7 AAPM Nuclear Medicine Committee Daniel J. Macey Lawrence E. Williams (Chairman) Hazel B. Breitz An Liu Timothy K. Johnson Pat B. Zanzonico April 2001 Published for the American Association of Physicists in Medicine by Medical Physics Publishing DISCLAIMER: This publication is based on sources and information believed to be reliable, but the AAPM and the editors disclaim any warranty or liability based on or relating to the contents of this publication. The AAPM does not endorse any products, manufacturers, or suppliers. Nothing in this publication should be interpreted as implying such endorsement. Further copies of this report ($10 prepaid) may be obtained from: Medical Physics Publishing 4513 Vernon Blvd. Madison, WI 53705-4964 Telephone: 1-800-442-5778 or 608-262-4021 Fax: 608-265-2121 Email: [email protected] Web site: www.medicalphysics.org International Standard Book Number: 1-888340-29-0 International Standard Serial Number: 0271-7344 2001 by the American Association of Physicists in Medicine One Physics Ellipse College Park, MD 20740-3843 All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means (electronic, mechan- ical, photocopying, recording, or otherwise) without the prior written permission of the publisher. Published by Medical Physics Publishing 4513 Vernon Blvd., Madison, WI 53705-4964 Printed in the United States of America TABLE OF CONTENTS Terms for Internal Dosimetry ............................................................................vii I. RADIONUCLIDE THERAPY PRINCIPLES...........................................1 A. Objectives and Scope of the Primer ....................................................1 B. Dose Estimation Relationships............................................................1 C. Properties of the S Matrix....................................................................3 1. Non-Penetrating (Charged Particle) Radiation ...............................3 2. Penetrating (Photon) Radiation.......................................................3 D. Historical Background.........................................................................4 E. The Tracer Principle ............................................................................4 F. Treatment Planning for Radioimunotherapy .......................................5 G. Toxicity and Efficacy...........................................................................5 II. PROTOCOL DESIGN FOR RADIONUCLIDE THERAPY....................6 A. What Biological Data are Required ....................................................6 B. Design of Dose Estimation Protocol for Radioimmunotherapy.....................................................................6 C. Dose Estimation in Humans from Murine Biodistribution Data ............................................................................7 III. CLINICAL ASPECTS OF RADIOIMMUNOTHERAPY TRIALS.........9 A. Patient Eligibility.................................................................................9 B. Administration of Radiolabeled Antibody.........................................10 1. Intravenous Injections...................................................................11 2. Intraperitoneal Injections ..............................................................11 3. Intra-Arterial Injections ................................................................13 4. Intralesional Injections..................................................................13 C. Patient Monitoring After Radiolabeled Antibody Administration.....14 D. Repeat Injections of the Same Antibody ...........................................15 E. Protein Preloading .............................................................................15 IV. ACQUISITION OF PHARMACOKINETIC PATIENT DATA..............16 A. Biological Data of Interest.................................................................16 1. Blood Activity...............................................................................16 2. Whole Body Retention..................................................................16 3. Other Normal Organ and Tumor Activity.....................................17 4. Minimal Levels of Uptake for Visualization.................................18 B. Uptake Measurements in Vivo ...........................................................18 1. Attenuation Corrections................................................................18 2. Scatter Correction Techniques ......................................................21 3. Use of Geometric Data from Anatomic Imaging..........................22 4. Quantitative SPECT Imaging .......................................................24 iii C. Organ and Tumor Volumes................................................................25 1. Palpation .......................................................................................25 2. Imaging Methods to Determine Organ Mass................................25 V. DATAANALYSIS METHODS...............................................................26 A. Activity and Percent Injected Activity (PIA) ....................................26 B. Justifications for Data Modeling .......................................................26 C. Types of Models ................................................................................27 1. Individual Organ Curve Fitting via Multi-Exponential Functions ........................................................27 2. Compartmental Modeling of the Entire Physiological System.....28 D. Which Data to Analyze......................................................................28 E. Physical Decay as a Clearance Mechanism in the Model .................30 F. Integration of Area Under the Curve (AUC).....................................31 1. Mathematical Form.......................................................................31 2. Multiple Exponential Functions....................................................31 3. Compartmental Model ..................................................................31 4. Variation of the Radionuclide .......................................................33 VI. DOSE CALCULATION METHODS AND PROGRAMS .....................33 A. Normal Organ Dose Estimates in Standard Man...............................33 1. MIRD 11 Pamphlet S Values ........................................................33 2. MIRDOSE2 and MIRDOSE3.......................................................34 3. Bone Marrow Dose Estimation.....................................................35 B. Patient-Specific Normal Organ Doses...............................................37 1. Target Organ Mass Correction......................................................37 2. Convolution Dose Estimates.........................................................38 3. Voxel Source Kernel Method........................................................39 C. Tumor Dose Estimations in Radioimmunotherapy and Radionuclide Therapy.................................................................39 1. Alpha and Auger Emissions..........................................................40 2. Beta Emissions..............................................................................40 a. Uniform Uptake.......................................................................40 b. Non-Uniform Uptake...............................................................40 3. The Tumor à Algorithm ...............................................................41 4. Tumor Mass Determination ..........................................................41 5. Computational Algorithms............................................................42 6. Photon Contributions to Tumor Dose Estimates...........................43 7. Clinical Computations (Beta and Photon Contributions Combined)..............................................................44 8. Dose to Tumors That Are Not Imaged..........................................44 9. Treatment Strategy and Results ....................................................45 iv VII. THYROID CANCER THERAPY - THYROID THERAPY WITH 131I..............................................................................46 VIII. BONE PAIN PALLIATION WITH RADIOPHARMACEUTICALS.....48 A. Clinical Situation...............................................................................48 B. Radionuclides ....................................................................................48 C. Dose Estimation.................................................................................49 IX. RADIATION PROTECTION CONSIDERATIONS ..............................50 A. General Radiation Safety...................................................................50 B. Discharge of Patients with Radioactivity from Hospital...................51 X. SUMMARY OF RADIOIMMUNOTHERAPY AND RADIONUCLIDE THERAPY IN CLINICAL PRACTICE ..................................................53 A. Treatment Planning............................................................................53 B. Clinical RIT Results ..........................................................................53 C. Limitations of the RIT Method..........................................................54 D. Other Internal Emitter Therapies.......................................................54 REFERENCES ..................................................................................................55
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