METAL IONS INBIOLOGICAL SYSTEMS

Astrid SigelHelmut Sige l

VOLUME 42

Metal Complexes in Tumor Diagnosi sand as Anticancer Agents

PREFACE TO THE SERIE S

PREFACE TO VOLUME 42

v

CONTRIBUTORS

xv

CONTENTS OF PREVIOUS VOLUMES

xix

HANDBOOK ON TOXICITY OF INORGANIC COMPOUNDS liv

HANDBOOK ON METALS IN CLINICAL AND

liv

ANALYTICAL CHEMISTRY

HANDBOOK ON METALLOPROTEINS

liv

Chapter 1

MAGNETIC RESONANCE CONTRAST AGENTS FOR MEDICA L

AND MOLECULAR IMAGING

1

Matthew J. Allen and Thomas J. Meade1. Introduction

2

2. Contrast Agents for Diagnosis

5

3. Targeted Delivery of Contrast Agents

1 1

4. Imaging Biochemical Events

1 4

5. Conclusions and Outlook

26

Acknowledgments

26

Abbreviations

26

References

28

Chapter 2

LUMINESCENT LANTHANIDE PROBES AS DIAGNOSTI C

AND THERAPEUTIC TOOLS

3 9

Jean-Claude G . Bünzl i1 . Lanthanide-Based Luminescent Probes : Why?

40

2. Designing a Lanthanide-Based Luminescent Probe

443. Applications in Medical Diagnosis

574. Use of Lanthanide Complexes in Photodynamic Therapies

655. Concluding Remarks

70Acknowledgments

7 1Abbreviations

7 1References

72

Chapter 3RADIOLANTHANIDES IN NUCLEAR MEDICINE

77Frank Rösch and Eva Forssell-Aronsson1. Introduction

782. Radiolanthanide Production

793. Labelling Chemistry and Labelled Compounds

82

4. Application of Radiolanthanide Radiopharmaceuticals

845. Conclusion

99Abbreviations

100References

10 1

Chapter 4RADIOMETALLO-LABELED PEPTIDES IN TUMOR DIAGNOSI SAND THERAPY

109Mihaela Ginj and Helmut R . Maecke1. Introduction

11 02. Radiometals of Interest for Peptide Labeling and Labelin g

Approaches

11 63. In Vitro Characterization of Radiometallo-Peptides

1244. Animal Models to Study Targeting of Tumors . Biodistribution

Therapy Studies

12 85. Influence of the (Radio)Metal Ion and Its Coordinatio n

Chemistry on the Targeting Properties of Radiometallo-Peptides 13 06. Overview of Patient Studies

13 37. Summary and Conclusion

13 7Abbreviations

13 7References

139

Chapter 5CISPLATIN AND RELATED ANTICANCER DRUGS :RECENT ADVANCES AND INSIGHTS

143Katie R . Barnes and Stephen J. Lippard1. Introduction

1442. Mechanism of Action

1453. Cellular Defenses Against Cisplatin

1604. Novel C-isplatinum Analogs as Anticancer Compounds

1635. Conclusions and Future Directions

167Acknowledgment

168Abbreviations

168References

169

Chapter 6THE EFFECT OF CYTOPROTECTIVE AGENTS I NPLATINUM ANTICANCER THERAPY

179Michael A. Jakupec, Markus Galanski, and Bernhard K. Keppler1. Toxicity Associated with Platinum Anticancer Therapy

1792. Overview of Cytoprotective Approaches

18 33. Amifostine

1864. Glutathione

1905. BNP7787 (Dimesna)

1946. a-Tocopherol (Vitamin E)

1957. a-Lipoic Acid

1968. Concluding Remarks

196Abbreviations

198References

198

Chapter 7ANTITUMOR ACTIVE TRANS-PLATINUM COMPOUNDS

209Giovanni Natile and Mauro Colucci a1. Introduction

21 02. Antitumor Active Trans-Platinum Compounds

22 13. Conclusions and Perspectives

23 9Acknowledgments

241Abbreviations and Definitions

241References

242

Chapter 8

POLYNUCLEAR PLATINUM DRUGS

25 1

Nicholas Farrel l

1. Introduction

252

2. Structural Variations within Polynuclear Platinum Complexes

25 3

3. DNA Binding Modes of Polynuclear Platinum Drugs

26 1

4. Trifunctional Dinuclear Platinum Complexes . Ternary

DNA-Protein Crosslinking

274

5. Polynuclear Platinum Complexes Bind Faster t o

Single-Stranded DNA

277

6. Biological Activity of Polynuclear Platinum Compounds

282

7. Clinical Experience

28 7

8. Conclusions

28 8

Acknowledgments

289

Abbreviations

290

References

290

Chapter 9

PLATINUM(IV) ANTICANCER COMPLEXES

297

Matthew D . Hall, Rachael C. Dolman, and Trevor W. Hambley

1. Introduction

298

2. History

298

3. Mechanism of Action

300

4. Design

30 1

5. Synthesis

307

6. In Vitro Interactions with Biomolecules

31 0

7. Biological Fate

311

8. Conclusions

31 6

Acknowledgments

31 6

Abbreviations

31 6

References

31 7

Chapter 1 0

RUTHENIUM ANTICANCER DRUGS

323

Enzo Alessio, Giovanni Mestroni, Alberta Bergamo, and Gianni Sav a

I . Introduction

324

2 . Chemical Features

325

3. Pharmacological Control of Tumor Growth

3344. Conclusions

344Acknowledgments

346Abbreviations

346References

347

Chapter 1 1ANTITUMOR TITANIUM COMPOUNDS AND RELATEDMETALLOCENES

353Francesco Caruso and Miriam Rossi1. Introduction

3542. Evolution of Titanium Drugs in Physiological Medium

3583. Potential Targets

3604. Attachment to Carriers

3625. Structure-Activity Studies

3626. Phase II Clinical Trials of Titanocene Dichloride

3687. Non-Titanium Metallocenes

3698. Conclusions Regarding Titanium-Based Antitumor Drugs

376Acknowledgments

378Abbreviations and Definitions

378References

379

Chapter 1 2GOLD COMPLEXES AS ANTITUMOR AGENTS

385Luigi Messori and Giordana Marco n1. Introduction

3862. Main Chemical Features of Gold Complexes

3883. Gold(I) Complexes as Antitumor Agents

3904. Gold(III) Complexes as Antitumor Agents

3995. Conclusions and Perspectives

41 9Acknowledgments

420Abbreviations

420References

421

Chapter 1 3GALLIUM AND OTHER MAIN GROUP METAL COMPOUND SAS ANTITUMOR AGENTS

425Michael A . Jakupec and Bernhard K. Keppler

1. Introduction

4262. "Simple Gallium Salts"

4273. Gallium Complexes

44 14. Other Main Group Metal Compounds in Cancer Therapy

4485. Summary and Conclusions

449Abbreviations

45 1References

45 1

Chapter 1 4METAL ION DEPENDENT ANTIBIOTICS I NCHEMOTHERAPY

463David H. Petering, Chuanwu Xia, and William E. Antholine

1. Introduction

4642. Direct Requirements of Antibiotics for Metal Ions : Mechanism 46 8

of Action of Bleomyci n3. Indirect Requirements of Antibiotics for Metal Ions : Mechanism 47 8

of Action of Doxorubicin4. Survey of Metal-Linked Antibiotics

4855. Discussion

488Acknowledgments

48 8Abbreviations and Definitions

488References

489

SUBJECT INDEX

499