U.S. MARKET FOR
THERAPEUTIC RADIOPHAMACEUTICALS
TABLE OF CONTENTS
Section
1.0 MARKET STATUS, TRENDS AND FORECASTS
1.1 INTRODUCTION AND OVERVIEW
1.1.1 Diagnostic-Therapeutic Pairs of Radiopharmaceuticals
1.1.2 New Targeted Therapy Agents
1.1.3 Radiotherapeutic Pipeline Products
1.1.4 Major Progress in International Cooperation
1.1.5 Russian-American Cancer Alliance
1.1.6 Relationships with Non-Members of the Alliance
1.1.7 New Technology Opportunities
1.1.8 Increased Use of Alpha Emitters
1.1.9 Importance of Patient Specific Dosimetry
1.2 THERAPEUTIC PRODUCT SALES AND MARKET FORECASTS
1.2.1 Sales Summary by Procedure Category and Product Type
1.2.2 Price Per Dose Assumptions
1.2.3 Lymphoma Therapy
1.3 OTHER SOFT TUMORS APPLICATIONS
1.3.1 Multiple Myeloma and Bone Cancer
1.3.2 Endocrine Cancer
1-10
1-11
1-12
1-14
1-16
1-16
1-26
1-29
1-33
1-33
1-35
Page
1-1
1-1
1-3
1-4
1-4
1-8
1-9
—————————————————————-———————————————————
Bio-Tech Systems, Inc. i Report 230

TABLE OF CONTENTS
Section
1.4 PRODUCTS FOR TREATING SOLID TUMORS
1.4.1 Lung Cancer Therapy
1.4.2 Prostate Cancer Therapy
1.4.3 Breast Cancer Therapy
1.4.4 Colon Cancer Therapy
1.4.5 Pancreatic Cancer and Liver Cancer Therapy
1.4.6 Malignant Melanoma Therapy
1.4.7 Other Solid Tumors
1.5 BONE PAIN PALLIATION
1.5.1 Bone Palliation Product Mix
1.5.2 Sales Forecasts
2.0 ANALYSIS OF PROCEDURE VOLUME
2.1 INTRODUCTION AND OVERVIEW
2.2 TARGETED RADIOTHERAPY PROCEDURES
2.3 ANALYSIS OF DATA SOURCES AND METHODOLOGY
2.3.1 Sources of Procedure Data
2.3.2 Advantages and Limitations of Available Data Bases
2.3.2.1 Advantages of Using Existing Data Bases
2.3.2.1 Limitations of Some of the Available Data Bases
2.3.3 CMS Medicare Data
2.3.4 Impact of Reimbursement on Procedure Coding
2-3
2-4
2-5
2-6
2-6
1-54
1-54
1-55
2-1
2-1
2-7
2-7
2-8
Page
1-38
1-40
1-45
1-45
1-46
1-47
1-50
1-53
—————————————————————-———————————————————
Bio-Tech Systems, Inc. ii Report 230

TABLE OF CONTENTS
Section
3.0 RADIOPHARMACEUTICAL PRODUCTS AND TECHNOLOGY
4.0
3.1 TYPES OF RADIOPHARMACEUTICAL PRODUCTS
3.2 FUNCTIONAL CHARACTERISTICS
3.2.1 Radiopharmaceutical Selection
3.3 RADIOISOTOPE PRODUCTION METHODS
3.3.1 Nuclear Reactors
3.3.2 Accelerators
3.3.3 Radionuclide Generators
3.4 RADIOPHARMACEUTICAL PREPARATION
3.4.1
3.4.2
Commercial Radiopharmacies
New Radiopharmaceuticals
CURRENT DEVELOPMENTS AND EMERGING TECHNOLOGY
4.1 INTRODUCTION AND OVERVIEW
4.1.1 Treating Lymphoma with Radioimmunotherapy
4.1.2 Growing Prospects for Therapeutic Antibodies
4-2
4-2
4.2 CHARACTERISTICS OF THERAPEUTIC RADIOPHARMACEUTICALS 4-3
4.3 TREATMENTS FOR NON-HODGKINS LYMPHOMA
4.3.1 lodine-131 vs. Yttrium-90 Trade-Offs
4-4
4-6
3-16
3-17
3-18
4-1
4-1
Page
3-1
3-1
3-5
3-6
3-9
3-11
3-14
3-15
4.3.2 Calculating the Clearance Rate
4.3.3 Toxicity Issues
4.3.4 Product Stability and Effectiveness
4.3.5 Y-90 Epratuzumab (Immunomedics)
4-7
4-9
4-10
4-10
—————————————————————-———————————————————
Bio-Tech Systems, Inc. iii Report 230

TABLE OF CONTENTS
Section
4.4 NEW ANTIBODY PSMA PRODUCTS FOR PROSTATE CANCER
4.4.1 Trade-offs Between Lutetium-177 and Yttium-90
4.4.2 Realistic Options in Treating the Prostate Cancer Patient
4.4.3 Unique Aspect of Prostate Cancer Tumors
4.4.4 Advantages and Limitations of the PSA Test
4.4.5 Some Advantages of Lutetium-177
4.4.6 Use of Multiple Drugs and Modalities
4.4.7 Cytogen's PSMA Therapeutic Antibody
4.4.8 Agreement with Dow Chemical
4.5 NEW ANTIBODY DEVELOPMENTS BY IMMUNOMEDICS
4.5.1 Bispecific Antibodies And Pretargeting
4.5.2 Humanized PAM4 Antibody for Pancreatic Cancer
4.6 COTARA TUMOR NECROSIS THERAPY (TNT)
4.6.1 Iodine-131 Cotara for Brain Tumor Therapy
4.6.2 Cotara TNT for Lung Cancer Approved in China
4.7 TARGETING OF GRP RECEPTORS WITH AGONISTS
4.7.1 Bombesin Agonists and Subtypes
4.7.2 Tailoring Bombesin to Various Receptors
4.8 SKELETAL TARGETED RADIATION
4.8.1 Holmium-166 DOTMP for Bone Marrow Ablation
4.8.2 Other Dow Developments
4.9 OCTREOTIDE AND OCTREOTATE FOR ENDOCRINE TUMORS
4-21
4-22
4-23
4-23
4-24
4-18
4-18
4-18
4-19
4-20
Page
4-11
4-12
4-12
4-13
4-14
4-14
4-15
4-17
4-25
4-25
4-26
4-27
—————————————————————-———————————————————
Bio-Tech Systems, Inc. iv Report 230

TABLE OF CONTENTS
Section
4.10 TARGETING VASCULAR BEDS OF CANCERS
4.10.1 Endothelia Cell Behavior
4.10.2 Polymer Drug Delivery Systems
4.10.3 Enhanced Retention Permeability
4.10.4 Alpha Emitters
4.11 TARGETED ALPHA THERAPY WITH AN IN VIVO GENERATOR
4.11.1 Application in Disseminated Melanoma
4.11.2 Advantages of Alpha Particles in Melanoma Therapy
4.12 CONSIDERATIONS IN SELECTING THERAPEUTIC ISOTOPES
4.12.1 Lanthanide Series of Isotopes
4.12.2 Product Characteristics
4.12.3 Alpha Emitters
4.13 CANCER RETENTION OF PHOSPHOLIPID ETHER ANALOGS
4.13.1 Mechanism of Action
4.13.2 Phospholipid Ether Analogs
4.13.3 Design and Testing of PLE Analogs
4.13.4
Cellectar’s Lead Compound I-125-NM404
4.13.5 Targeting Non-Small Cell Lung Cancer
4.13.6 Use of PLE Technology in Diagnostic Imaging
5.0 END-USER ANALYSIS
5.1 OVERVIEW OF THE USER ENVIRONMENT
5.1.1 Organization of Nuclear Medicine Departments
4-38
4-39
4-40
4-41
4-41
4-35
4-36
4-37
4-37
4-38
Page
4-27
4-28
4-29
4-30
4-31
4-33
4-34
4-35
4-42
5-1
5-1
5-2
—————————————————————-———————————————————
Bio-Tech Systems, Inc. v Report 230

TABLE OF CONTENTS
Section
5.2 ALLOCATION OF HOSPITAL NUCLEAR MEDICINE EQUIPMENT
5.3 COMPARATIVE UTILIZATION PARAMETERS
5.4 DISTRIBUTION OF IMAGING PROCEDURES
5.4.1 Relative Diagnostic Activity
5.4.2 Relative Procedure Volume
5.4.3 Imaging Activity Index
5.4.4 Distribution of Nuclear Studies in Hospitals & Clinics
5.5 THE IN-HOSPITAL HOT LAB VS. COMMERCIAL PHARMACIES
5.5.1 Unit-Dose Packaging
5.5.2 Pricing Practices
5.5.3 Other Services
5.6 NONHOSPITAL END-USERS
5.7 ISSUES OF BOARD CERTIFICATION
6.0 COMPANY PROFILES
6.1 INTRODUCTION
6.2 ALGETA
6.3 ALPHAMED INC.
6.4 ANTISOMA LTD. (UK)
6.5 BERLEX LABORATORIES
6.6 BIOGEN IDEC INC.
6.7 BIO-NUCLEONICS, INC.
6.8 BOSTON LIFE SCIENCES
6-10
6-14
6-16
6-16
6-1
6-1
6- 3
6-5
6-7
5-14
5-15
5-16
5-17
5-18
Page
5-3
5-4
5-7
5-7
5-10
5-11
5-11
5-13
—————————————————————-———————————————————
Bio-Tech Systems, Inc. vi Report 230

TABLE OF CONTENTS 6-
Section
6.9 BRACCO DIAGNOSTICS
6.10 BRISTOL MYERS SQUIBB IMAGING
6.11 CARDINAL HEALTH
6.12 CELLECTAR, LLC
6.13 CIS BIO-INTERNATIONAL
6.14 CYTYC CORPORATION (PROXIMA THERAPEUTICS)
6.15 CYTOGEN CORPORATION
6.16 DOW CHEMICAL CO.
6.17 DRAXIMAGE, INC.
6.18 GE HEALTHCARE DIAGNOSTICS
6.19 GLAXO SMITHKLINE CORPORATION
6.20 IMMUNOMEDICS, INC.
6.21 LYNNTECH INC.
6.22 MALLINCKRODT INC. (TYCO HEALTHCARE)
6.23 MDS NORDION
6.24 MILLENIUM PHARMACEUTICALS
6.25 MOLECULAR INSIGHT PHARMACEUTICALS INC.
6.26 PALATIN TECHNOLOGIES INC.
6.27 PEREGRINE PHARMACEUTICALS INC.
6.28 SIRTEX MEDICAL LTD.
6-68
6-71
6.29 THERAGENICS CORPORATION 6-76
APPENDIX A
– LIST OF MANUFACTURERS OF RADIOPHARMACEUTICALS
A-1
6-54
6-57
6-60
6-63
6-66
Page
6-19
6-21
6-24
6-26
6-29
6-31
6-34
6-38
6-40
6-42
6-47
6-48
6-51
—————————————————————-———————————————————
Bio-Tech Systems, Inc. vii Report 230

U.S. MARKET FOR
THERAPEUTIC RADIOPHAMACEUTICALS
LIST OF EXHIBITS
Exhibit Page
1-1
1-2
1-3
1-4
1-5
1-6
1-7
1-8
THERAPEUTIC ANTIBODIES APPROVED TO DATE
2005 THERAPEUTIC RADIOPHARMACEUTICAL SALES SUMMARY
BY PROCEDURE CATEGORY AND PRODUCT TYPE
1-5
THERAPEUTIC PIPELINE PRODUCTS 1-7
HISTORIC AND FORECAST PROCEDURE VOLUME AND SALES OF 1-17
THERAPEUTIC RADIOPHARMACEUTICALS FROM 2002-2012
1-18
2008 THERAPEUTIC RADIOPHARMACEUTICAL SALES SUMMARY
BY PROCEDURE CATEGORY AND PRODUCT TYPE
2012 THERAPEUTIC RADIOPHARMACEUTICAL SALES SUMMARY
BY PROCEDURE CATEGORY AND PRODUCT TYPE
1-19
1-22
HISTORIC AND FORECAST SALES OF THERAPEUTIC RADIO-
PHARMACEUTICALS BY PRODUCT CATEGORY FROM 2002-2012
1-25
HISTORIC AND FORECAST PROCEDURE GROWTH OF THERAPEUTIC 1-27
RADIOPHARMACEUTICALS BY PRODGROUP FROM 2002-2012
1-9 HISTORIC AND FORECAST SALES GROWTH OF LYMPHOMA
AGENTS BY MANUFACTURER AND PRODUCT TYPE FROM 2002-2012
1-30
1-10 HISTORIC AND FORECAST GROWTH OF LYMPHOMA RADIO-
THERAPY PROCEDURES BY MANUFACTURER AND PRODUCT TYPE
FROM 2002-2012
1-31
1-11 FORECAST SALES OF NEW THERAPEUTIC RADIOPHARMA- 1-36
CEUTICALS FOR MYELOMA, BONE CANCER AND ENDOCRINE TUMORS
FROM 2008-2012
1-37 1-12 FORECAST GROWTH OF NEW RADIOPHARMACEUTICAL
PROCEDURES FOR MYELOMA, BONE CANCER AND ENDOCRINE
TUMORS FROM 2008-2012
1-13 FORECAST SALES OF NEW THERAPEUTIC RADIOPHARMA-
CEUTICALS FOR TREATING SOLID TUMORS BY DISEASE
TYPE FROM 2008-2012
1-39
—————————————————————-———————————————————
Bio-Tech Systems, Inc. viii Report 230

LIST OF EXHIBITS
Exhibit Page
1-14 FORECAST PROCEDURE VOLUME FOR NEW RADIOPHARMA-
CEUTICALS FOR TREATING SOLID TUMORS BY DISEASE TYPE
FROM 2008-2012
1-15 FORECAST SALES OF NEW RADIOPHARMACEUTICALS FOR
LUNG CANCER, PROSTATE CANCER AND BREAST CANCER
BY PRODUT FROM 2008-2012
1-16 FORECAST NEW PROCEDURE GROWTH FOR FOR LUNG
CANCER,PROSTATE CANCER AND BREAST CANCER
FROM 2008-2012
1-17 FORECAST SALES OF RADIOPHARMACEUTICALS FOR,
COLON CANCER PANCREATIC CANCER AND LIVER CANCER
BY PRODUCT FROM 2008-2012
1-41
1-43
1-44
1-48
1-18 FORECAST GROWTH OF NEW PROCEDURES FOR COLON
CANCER, PANCREATIC CANCER AND LIVER CANCER BY PRODUCT
FROM 2008-2012
1-49
1-51 1-19 FORECAST SALES OF NEW RADIOPHARMACEUTICALS
FOR MELANOMA, BRAIN CANCER AND OTHER SOLID TUMORS
BY PRODUCT FROM 2008-2012
1-20 FORECAST PROCEDURE GROWTH FOR NEW RADIOPHARMA-
CEUTICALS FOR MELANOMA, BRAIN CANCER AND OTHER
TUMORS FROM 2008-2012
1-52
1-56 1-21 HISTORIC AND FORECAST SALES GROWTH OF BONE PAIN
PALLIATION RADIOTHERAPY AGENTS BY PRODUCT TYPE
FROM 2002-2012
2-1 GROWTH OF RADIOTHERAPY PROCEDURE VOLUME
FROM 2005-2012
3-1
5-1
5-2
DIAGNOSTIC AND THERAPEUTIC ISOTOPES
COMPARATIVE ALLOCATION OF DIAGNOSTIC FACILITIES
BY HOSPITAL BED SIZE IN 2005
COMPARATIVE UTILIZATION PARAMETERS
FOR DIFFERENT IMAGING MODALITIES IN 2005
2-4
3-4
5-5
5-6
—————————————————————-———————————————————
Bio-Tech Systems, Inc. ix Report 230

LIST OF EXHIBITS
Exhibit Page
5-3
5-4
5-5
DISTRIBUTION OF HOSPITAL DIAGNOSTIC IMAGING PROCEDURES 5-8
IN THE U.S. BY HOSPITAL BED SIZE IN 2005
5-9 RELATIVE PROCEDURE VOLUME FOR DIFFERENT IMAGING
MODALITIES, PERCENTAGE RELATIONSHIP BY HOSPITAL
BED SIZE IN 2005
RELATIVE ACTIVITY INDEX AMONG DIFFERENT IMAGING
MODALITIES, PROCEDURES PER BED PER YEAR BY HOSPITAL
BED SIZE IN 2005
5-11
—————————————————————-———————————————————
Bio-Tech Systems, Inc. x Report 230