PART I. OVERVIEW OF THE COORDINATED RESEARCH PROJECT
CHAPTER 1. OBJECTIVES, RESULTS AND ACHIEVEMENTS OF
THE COORDINATED RESEARCH PROJECT ................... 3
1.1. Introduction ........................................... 3
1.2. Objectives of the coordinated research project ......... 7
1.3. Overview of the work plan .............................. 7
1.4. Scientific achievements of the coordinated research
project ............................................... 10
1.5. Conclusion and recommendations ........................ 12
CHAPTER 2. PREPARATION AND QUALITY CONTROL OF
177Lu-DOTATATE FOR TARGETED THERAPY ................ 17
2.1. Materials ............................................. 17
2.2. Preparation of 177Lu-DOTATATE .......................... 19
2.3. Quality control ....................................... 20
2.4. Storage of radiolabeled peptide ....................... 21
2.5. In vitro stability .................................... 21
2.6. Conclusion ............................................ 22
PART II. REPORTS BY PARTICIPANTS IN THE COORDINATED
RESEARCH PROJECT
CHAPTER 3. DEVELOPMENT OF SOMATOSTATIN BASED RADIO-
PHARMACEUTICALS FOR RECEPTOR MEDIATED
RADIONUCLIDE THERAPY ............................... 27
E.B. Araújo, J.S. Caldeira Filho, L.T. Nagamati,
E. Muramoto, M.T. Colturato, R. Couto, K. Okasaki,
M.F. Suzuki, M.I.C.C. Guimaraes
3.1. Introduction .......................................... 27
3.2. Materials and methods ................................. 29
3.3. Results and discussion ................................ 35
3.4. Organ dosimetry ....................................... 45
3.5. Micronucleus assay .................................... 48
CHAPTER 4. BIOLOGICAL EVALUATION OF RADIOTRACERS FOR
RADIONUCLIDE THERAPY ............................... 53
G.J. Pimentel, R. Ravelo, M. Miranda, J.
Gavilondo, L. Pérez, M. Ayala, H. Bell, H.E.
Garay, O. Reyes, I. Sanchez
4.1. Introduction .......................................... 54
4.2. Materials and methods ................................. 55
4.3. Results and discussion ................................ 61
4.4. Conclusion ............................................ 70
CHAPTER 5. PRECLINICAL COMPARISON OF DOTATATE LABELLED WITH
DIFFERENT RADIONUCLIDES ............................ 73
M. Laznicek, A. Laznickova, F. Trejtnar, L.
Melicharova, J. Cihlo, M. Petrik
5.1. Introduction .......................................... 74
5.2. Materials and methods ................................. 74
5.3. Results and discussion ................................ 79
5.4. Conclusion ............................................ 85
CHAPTER 6. EVALUATION OF PEPTIDES LABELLED WITH BETA
EMITTING RADIONUCLIDES FOR RECEPTOR TARGETED
RADIOTHERAPY OF MALIGNANT TUMOURS .................. 87
T. Maina, B. Nock, A. Nikolopoulou, C. Petrou,
P. Cordopatis
6.1. Introduction .......................................... 88
6.2. Materials ............................................. 90
6.3. Methods ............................................... 91
6.4. Results ............................................... 95
6.5. Conclusion ........................................... 100
CHAPTER 7. LABELLING AND BIOLOGICAL EVALUATION OF
THERAPEUTIC RADIOPHARMACEUTICALS .................. 103
G.A. Jánoki, A. Polyák, R. Király, L. Balogh,
L. Kőrösi, D. Máthé
7.1. Introduction ......................................... 103
7.2. 188Re labelled bone seeking and tumour specific
agents for therapy ................................... 104
7.3. Radiolabelled receptor specific peptides for
targeted use in diagnosis and therapy ................ 112
CHAPTER 8. PREPARATION AND EVALUATION OF 177Lu-DOTATATE
FOR POTENTIAL APPLICATION IN PEPTIDE RECEPTOR
RADIONUCLIDE THERAPY .............................. 131
S. Banerjee, S. Chakraborty, A. Korde, T. Das,
A. Mukherjee, U. Pandey, H.D. Sarma, G. Samuel,
P.S. Dhami, A.D. Ingle, M. Venkatesh
8.1. Introduction ......................................... 132
8.2. Materials ............................................ 133
8.3. Methods .............................................. 134
8.4. Results and discussion ............................... 143
8.5. 177Lu labelling of other target specific ligands ...... 157
8.6. Conclusion ........................................... 161
CHAPTER 9. OPTIMIZATION OF LABELLING CONDITIONS AND CELL
BINDING ASSAY FOR 177Lu-DOTATATE ................... 163
M. Chinol, Sun Ju Choi
9.1. Introduction ......................................... 163
9.2. Materials and methods ................................ 164
9.3. Results .............................................. 166
9.4. Conclusion ........................................... 168
CHAPTER 10. COMPARATIVE EVALUATION OF LABELLED BIOMOLECULES
FOR TARGETED RADIOTHERAPY ......................... 169
S.J. Choi, Y.D. Hong, S.M. Choi
10.1. Introduction ......................................... 169
10.2. Materials and methods ................................ 171
10.3. Results .............................................. 173
10.4. Conclusion ........................................... 177
CHAPTER 11. LABORATORY METHODS TO EVALUATE THERAPEUTIC
RADIOPHARMACEUTICALS .............................. 181
C. Arteaga de Murphy, G. Ferro-Flores, J.
Rodriguez-Cortes, M. Pedraza-Lopez, M.T.
Ramirez-Iglesias
11.1. Introduction ......................................... 181
11.2. Materials and methods ................................ 183
11.3. Results .............................................. 188
11.4. Discussion and conclusion ............................ 192
CHAPTER 12. LABORATORY EVALUATION OF THE BETA EMITTING
RADIONUCLIDES 177Lu, 131I,153Sm AND 166Ho,
AND RADIOPHARMACEUTICALS FOR RADIOTHERAPY ......... 197
M.M. Ishfaq, H.J. Nizakat, K.M. Bashar,
I. Haider
12.1. Introduction ......................................... 198
12.2. Materials ............................................ 199
12.3. Methods .............................................. 199
12.4. Results and discussion ............................... 204
CHAPTER 13. PRECLINICAL EVALUATION OF THERAPEUTIC
RADIOPHARMACEUTICALS BASED ON 90Y AND 177Lu ........ 217
D. Pawlak, A. Korsak, R. Mikolajczak, B. Janota,
U. Karczmarczyk, E. Jakubowska
13.1. Introduction ......................................... 217
13.2. Methods .............................................. 217
13.3. Results .............................................. 221
13.4. Conclusion ........................................... 231
CHAPTER 14. LABELLING OF DOTATATE WITH 177Lu AND 131I FOR
DIAGNOSIS AND TARGETED THERAPY: IN VITRO AND
IN VIVO COMPARATIVE EVALUATION .................... 233
V. Lungu, D. Niculae, D. Chiper, R. Mihai, L.
Danaila, S. Baiculescu
14.1. Introduction ......................................... 234
14.2. Materials ............................................ 234
14.3. Methods .............................................. 235
14.4. Results .............................................. 240
14.5. Conclusion ........................................... 254
CHAPTER 15. PRECLINICAL DEVELOPMENT OF THERAPEUTIC
RADIOPHARMACEUTICALS .............................. 257
S.J. Mather
15.1. Introduction ......................................... 257
15.2. Radiopharmaceutical design ........................... 258
15.3. Synthesis or purchase of precursor ................... 259
15.4. Radiolabelling development ........................... 260
15.5. Analyses of radiochemical purity ..................... 260
15.6. Stability assessment ................................. 261
15.7. Receptor binding ..................................... 262
15.8. Cellular processing and metabolism ................... 263
15.9. In vivo biodistribution and targeting ................ 264
15.10.In vitro and in vivo measures of efficacy ............ 265
CHAPTER 16. LABORATORY EVALUATION OF THERAPEUTIC
BIOMOLECULES LABELLED WITH RADIOIODINE
AND LUTETIUM ...................................... 269
H.S. Balter, P. Oliver, A. Robles, N. Berois,
P. Cabral, A. Nappa, A. López, V. Trindade, G.
Rodríguez, S. Lanzzeri, S. Verdera
16.1. Introduction ......................................... 270
16.2. Materials ............................................ 271
16.3. Methods .............................................. 271
16.4. Results .............................................. 278
16.5. Conclusion ........................................... 290
APPENDIX I: PROTOCOLS DEVELOPED AS PART OF THE COORDINATED
RESEARCH PROJECT ................................. 295
APPENDIX II: PAPERS PUBLISHED BY THE PARTICIPANTS RELATED
TO THE COORDINATED RESEARCH PROJECT ............. 306
LIST OF PARTICIPANTS .......................................... 311
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