Yttrium-90 and Rhenium-188 Radiopharmaceuticals for Radionuclide Therapy

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DPD and HEDP, the encouraging results using 90 Y MDP, 90 Y DPD and 90 Y HEDP gave the impetus to undertake the present study. 10.3.2. Preparation of 90 Y complexes of DMSA The objective of the study was labelling of meso-DMSA with 90 Y, whereby a labelled complex for therapy of bone malignancies and for bone pain palliation could be prepared [10.6]. 10.3.2.1. Materials and methods The labelling with 90 Y was carried out using varying experimental parameters such as ligand concentration, pH, reaction time and temperature to maximize the labelling yield. The stock solutions of DMSA were prepared with double distilled water. The desired amounts of ligands (0.01–10 mg/mL) were placed in different vials. Then, ~370 MBq of 90 Y chloride was added to each vial. The pH of the resulting reaction mixtures was adjusted either to 3.0 or 8.0, and maintained at 8.0 using 0.1 mol/dm 3 phosphate buffer. The total reaction volume in each vial was kept at 3 mL. Ascorbic acid (10 mg) was used as the radiolytic stabilizer in all samples. Reagent concentrations and reaction time were optimized at the most suitable pH value. Analysis of the complexes included RCP (ITLC, paper chromatography and HPLC), determination of pharmacokinetic parameters, serum stability and organ distribution studies in healthy male Wistar rats. Wistar rats weighing 100–120 g (n = 3–5 for each time point) were injected with 0.1 mL (18.5–37.0 MBq) of the labelled complex via the tail vein and then sacrificed at 2 and 24 h p.i. UV absorption spectra of reference yttrium solutions (metal concentration of 0.50mM) with increasing concentrations of meso-DMSA were collected. A possible molecular structure of the complex 90 Y DMSA was proposed according to molecular modelling calculations. Molecular modelling studies were carried out using HyperChem software for Windows (release 6.03). 10.3.2.2. Results and discussion HPLC radiochromatograms of the labelling mixture showed good separation of 90 Y DMSA from free 90 Y with retention time R t = 5.63 and 6.55 min, respectively. The stability of the 90 Y DMSA complex was studied at various time points. After preparation, 90 Y DMSA (with and without ascorbic acid and at pH8.0) was incubated at room temperature for 24 h and the RCP was analysed. Yttrium-90 DMSA solutions, including ascorbic acid as the stabilizer, retained their initial RCP (95%) after 24 h incubation. The serum stability of 90 Y DMSA 180
was assessed by measuring the release of 90 Y from the complex at 37°C over a 10 d period. It was found that the complex with ascorbic acid was stable at different time points up to 10 d, with no significant dissociation of activity from the complex (
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IAEA RADIOISOTOPES AND RADIOPHARMAC
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YTTRIUM-90 AND RHENIUM-188 RADIOPHA
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IAEA RADIOISOTOPES AND RADIOPHARMAC
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FOREWORD The IAEA helps to promote
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CONTENTS CHAPTER 1. INTRODUCTION ..
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7.4. Discussion ...................
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CHAPTER 12. DEVELOPMENT OF 90 Sr/ 9
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Chapter 1 INTRODUCTION 1.1. BACKGRO
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devices were designed to improve th
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etention of the antibody’s target
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Binding affinity of these derivativ
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Chapter 2 FUNDAMENTAL CONCEPTS IN R
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A special characteristic of radioph
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β particles emitted by 90 Y. Numer
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2.3.1. Exploitation of certain meta
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2.3.3. Antibodies The high specific
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cell cultures, presents one example
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Another very promising form of radi
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destructive processes within the jo
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esearch efforts, since then. Howeve
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[2.18] HAMILTON, J.G., The metaboli
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[2.52] GOLDENBERG, D.M., et al., Mu
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Chapter 3 DEVELOPMENT OF RADIOPHARM
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FIG. 3.3. Elution efficiencies for
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FIG. 3.5. Electrodeposition of yttr
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The results of the experiments of r
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TABLE 3.3. RESULTS FOR 90 Sr/ 90 Y
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FIG. 3.11. Elution yield of a 90 Sr
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According to Fig. 3.12, there is a
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eagent (Sigma). The mean recovery o
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FIG. 3.18. Variation of RCP (%) of
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(20 and 30 min) and volume of 188 R
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FIG. 3.24. Variation of labelling y
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(c) Clodronate: 20 mg of clodronate
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Chapter 4 EVALUATION OF THE 90 Sr/
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Kamadhenu consists of five main com
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Quality control of radiolabelling w
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The electrochemical deposition of 9
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FIG. 4.5. Typical pattern of the wh
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FIG. 4.6. Elution profile from the
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FIG. 4.8. CD20 recognition in Ramos
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4.5. RECOMMENDATIONS AND FUTURE WOR
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adioiodine labelled anti-NCAM antib
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FIG. 5.1. Comparison of biodistribu
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FIG. 5.3. Three step strategy. Biot
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TABLE 5.1. THREE STEP PRETARGETING:
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5.1.4. Therapeutic experiments with
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5.1.4.4. Conclusion The radioiodine
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control procedure for detection of
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6.1.3. Recovery of doped 85/89 Sr 2
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6.2. PREPARATION AND BIOEVALUATION
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(a) (b) (c) FIG. 6.5. PD-10 column
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FIG. 6.7. SDS PAGE pattern of ritux
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FIG. 6.10. HPLC pattern of pure 90
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FIG. 6.13. Cell binding studies wit
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6.2.1.6. Conclusion The procedure f
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FIG. 6.17. Elution profile of 90 Y
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form NADH, which, in turn, causes t
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FIG. 6.19. In vivo distribution pat
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ACKNOWLEDGEMENTS The authors of thi
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Chapter 7 DEVELOPMENT OF THERAPEUTI
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the residual breast tissue becoming
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7.2.5.2. Automatic procedure The la
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FIG. 7.2. RCP values of 90 Y r-BHD
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FIG. 7.3. Pyrogen test shows result
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to avidin at the 1:4 avidin:r-BHD m
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[7.9] SU, F.M., GUSTAVSON, L.M., AX
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8.1. INTRODUCTION In past years, th
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(a) FIG. 8.1. (a) Schematic illustr
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Preliminary synthesis of the biotin
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(a) (b) FIG. 8.4. (a) PEGylated and
Page 143 and 144: TABLE 8.2. BIODISTRIBUTION IN RATS
Page 145 and 146: A specific binding to avidin was ev
Page 147 and 148: [8.13] BOSCHI, A., DUATTI, A., UCCE
Page 149 and 150: 90 Y solution obtained from a 90 Sr
Page 151 and 152: From each fraction, a ~1 g aliquot
Page 153 and 154: FIG. 9.2. Relationship between 90 S
Page 155 and 156: with 188 Re obtained from the 188 W
Page 157 and 158: 9.3.2. Labelling of DPA ale DPA ale
Page 159 and 160: FIG. 9.8. TLC radiochromatogram of
Page 161 and 162: (-) 188 Re(CO) 3 (+) (-) 99m Tc(CO)
Page 163 and 164: the HSA solution containing sodium
Page 165 and 166: TABLE 9.3. RESULTS OF 99m Tc LABELL
Page 167 and 168: 9.4.4. Yttrium-90 and 177 Lu labell
Page 169 and 170: FIG. 9.14. In vitro stability of 90
Page 171 and 172: (a) (b) (c) (d) (e) (f) (g) (h) (i)
Page 173 and 174: TABLE 9.8. YTTRIUM-90 CITRATE COLLO
Page 175 and 176: (a) (b) FIG. 9.17. Grain size distr
Page 177 and 178: TABLE 9.10. BIODISTRIBUTION AFTER A
Page 179 and 180: FIG. 9.19. Structure of DOTA biotin
Page 181 and 182: [9.8] WESTERA, G., GADZE, A., HORST
Page 183 and 184: Chapter 10 DEVELOPMENT, PREPARATION
Page 185 and 186: acidic pH) and the vial heated for
Page 187 and 188: 10.2.2.1. Materials and methods (a)
Page 189 and 190: Using a semiquantitative method, th
Page 191 and 192: FIG. 10.3. Whole body, SPECT and ta
Page 193: TABLE 10.4. ORGAN DISTRIBUTION STUD
Page 197 and 198: —— Biological studies: The whol
Page 199 and 200: or liver) (see Fig. 10.7). The resu
Page 201 and 202: (b) Results and discussion Healthy
Page 203 and 204: and the pellet (particles of HA lab
Page 205 and 206: FIG. 10.11. Organ distribution stud
Page 207 and 208: The procedure was as follows: —
Page 209 and 210: TABLE 10.5. INFLUENCE OF CHEMICAL I
Page 211 and 212: analysed using ICP OES was within t
Page 213 and 214: suggested for separation of pure 86
Page 215 and 216: adionuclidic purity of the 90 Y sol
Page 217 and 218: FIG. 10.16. (a) Strontium-90/yttriu
Page 219 and 220: [10.5] DJOKIĆ, D.J., JANKOVIĆ, D.
Page 221 and 222: Yttrium-90 is one of the radionucli
Page 223 and 224: (a) (b) (c) The generator was prepa
Page 225 and 226: —— Development of EPC: The EPC
Page 227 and 228: FIG. 11.4. Elution curve of 90 Sr e
Page 229 and 230: 11.4. YTTRIUM-90 MAbs The use of th
Page 231 and 232: FIG. 11.6. RCP measured using ITLC
Page 233 and 234: FIG. 11.9. Biodistribution of 90 Y
Page 235 and 236: 11.5. YTTRIUM-90 EDTMP Bone metasta
Page 237 and 238: FIG. 11.14. Electrophoresis of 90 Y
Page 239 and 240: FIG. 11.15. Particle size distribut
Page 241 and 242: 11.7. CONCLUSION During this CRP, a
Page 243 and 244: Chapter 12 DEVELOPMENT OF 90 Sr/ 90
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12.1.1.4. Acid vapour trap and radi
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12.1.8. Yttrium-90 peptide labellin
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(a) FIG. 12.3. Yttrium-90 elution p
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FIG. 12.6. HPLC of 90 Y DOTATATE. 1
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Chapter 13 BIFUNCTIONAL BISPHOSPHON
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latter requirement [13.10]. When th
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whether the organometallic core sel
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The fate of a targeted imaging prob
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FIG. 13.7. SPECT/CT images showing
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FIG. 13.9. TLC SG analyses of [ 188
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FIG. 13.11. Stability study (toward
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Ex vivo biodistribution studies at
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was in the form of either pertechne
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FIG. 13.19. Absolute uptake of 99m
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[13.2] ZHANG, S., GANGAL, G., ULUDA
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[13.31] DE ROSALES, R.T.M., et al.,
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The activity due to 90 Sr should be
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14.3.1.2. Operation of the 90 Sr/ 9
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antibody were taken, to which 90 Y
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operation, radiopharmaceutical grad
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14.4.1.3. Operation of the stage II
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A typical EPC pattern for a 90 Y pr
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FIG. 14.10. Decay curve of carrier
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FIG. 14.12. ITLC of 90 Y rituximab.
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FIG. 14.13. Reaction scheme for lab
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TABLE 14.6. STABILITY (%) OF 90 Y D
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FIG. 14.18. Microsphere albumin siz
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[14.3] PANDEY, U., DHAMI, P.S., JAG
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naphthalene and 1.2 g of 2,5-diphen
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A-2.2. Materials The method for sep
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out using a Wallac 1411 spectromete
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A-5.3. Procedure The technique was
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Although acyclic chelators offer ma
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(b) (c) and 90 Y colloids, both ser
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CONTRIBUTORS TO DRAFTING AND REVIEW
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INDIA Allied Publishers 1 st Floor,
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A key requirement for the effective
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Yttrium-90 and Rhenium-188 Radiopharmaceuticals for Radionuclide Therapy

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