Yttrium-90 and Rhenium-188 Radiopharmaceuticals for Radionuclide Therapy

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FIG. 5.4. Reduction of tumour volume in neuroblastoma bearing mice after application of 90 Y DOTA ERIC1 in different activities, in comparison with a control group. Iodine-131 MIBG did not show a detectable influence on tumour growth when activities up to 10 MBq/animal were administered, while 131 I ERIC1, as in earlier studies [5.4], showed a therapeutic effect, even when markedly low doses of radioactivity were injected. In contrast, in the control group, where the cold ERIC1 antibody was injected, no reduction or slowing of tumour growth was observed in comparison to the controls. The influence of fractionation on the therapeutic effect could be studied previously only with 131 I ERIC1, wherein on application of single doses of 2 MBq of 131 I ERIC1 every three days, fast accumulation of activity of up to >4 MBq 131 I was seen in the animal. Thus, in this group, the therapeutic action was intensified, albeit with an increased lethality, with the animals dying 13–16 d p.i. free of tumours. An injected dose of 0.5 MBq 131 I was found to be effective, and, with this treatment, the animals did not show adverse side effects such as weight loss or increased lethality, but survived for more than six months. The future plan is to investigate whether fractionation has a favourable influence on the therapeutic outcome with 90 Y ERIC1, that is, if it reduces side effects, as 90 Y applied at activities of >1 MBq usually leads to massive weight loss and death in the animals treated. 80
5.1.4.4. Conclusion The radioiodine labelled anti-NCAM antibody ERIC1 seems to be a promising radiopharmaceutical for treatment of neuroblastoma. The optimal dose is 1–2 MBq/animal, which would correspond to ~600–1200 MBq in humans (for a child of 15 kg). Initial experiments with 90 Y labelled ERIC1 have been very promising. These antibodies have shown an unequivocal therapeutic effect, whereas 131 I MIBG appears to have no influence on the tumour growth, even when higher radioactivity is administered per animal. Future studies will focus on: (a) (b) (c) (d) (e) Improved dose finding studies; Fractionation of radiation dose realized by intravenous application of 90 Y labelled ERIC1; Investigation of other radioimmunoconstructs against NCAM; Investigation of other tumour types with NCAM on tumour cells (particularly, small cell lung carcinoma); Pretargeting. REFERENCES TO CHAPTER 5 [5.1] SCHOMÄCKER, K., et al., Radioimmunotherapy with yttrium-90 ibritumomab tiuxetan. Clinical considerations, radiopharmacy, radiation protection, perspectives, Nucl. Med. 44 (2005) 166. [5.2] PAGANELLI, G., CHINOL, M., Radioimmunotherapy: Is avidin-biotin pretargeting the preferred choice among pretargeting methods? Eur. J. Nucl. Med. Mol. Imaging 30 (2003) 773. [5.3] OTTO, C., et al., Localization of 131I-labelled monoclonal antibody ERIC1 in a subcutaneous xenograft model of neuroblastoma in SCID mice, Nucl. Med. Commun. 27(2) (2006) 171. [5.4] GOLDENBERG, D.M., ROSSI, E.A., SHARKEY, R.M., McBRIDE, W.J., CHANG, C.H., Multifunctional antibodies by the dock-and-lock method for improved cancer imaging and therapy by pretargeting, J. Nucl. Med. 49 (2008) 158. 81
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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
Page 43 and 44: [2.52] GOLDENBERG, D.M., et al., Mu
Page 45 and 46: Chapter 3 DEVELOPMENT OF RADIOPHARM
Page 47 and 48: FIG. 3.3. Elution efficiencies for
Page 49 and 50: FIG. 3.5. Electrodeposition of yttr
Page 51 and 52: The results of the experiments of r
Page 53 and 54: TABLE 3.3. RESULTS FOR 90 Sr/ 90 Y
Page 55 and 56: FIG. 3.11. Elution yield of a 90 Sr
Page 57 and 58: According to Fig. 3.12, there is a
Page 59 and 60: eagent (Sigma). The mean recovery o
Page 61 and 62: FIG. 3.18. Variation of RCP (%) of
Page 63 and 64: (20 and 30 min) and volume of 188 R
Page 65 and 66: FIG. 3.24. Variation of labelling y
Page 67 and 68: (c) Clodronate: 20 mg of clodronate
Page 69 and 70: Chapter 4 EVALUATION OF THE 90 Sr/
Page 71 and 72: Kamadhenu consists of five main com
Page 73 and 74: Quality control of radiolabelling w
Page 75 and 76: The electrochemical deposition of 9
Page 77 and 78: FIG. 4.5. Typical pattern of the wh
Page 79 and 80: FIG. 4.6. Elution profile from the
Page 81 and 82: FIG. 4.8. CD20 recognition in Ramos
Page 83 and 84: 4.5. RECOMMENDATIONS AND FUTURE WOR
Page 85 and 86: adioiodine labelled anti-NCAM antib
Page 87 and 88: FIG. 5.1. Comparison of biodistribu
Page 89 and 90: FIG. 5.3. Three step strategy. Biot
Page 91 and 92: TABLE 5.1. THREE STEP PRETARGETING:
Page 93: 5.1.4. Therapeutic experiments with
Page 97 and 98: control procedure for detection of
Page 99 and 100: 6.1.3. Recovery of doped 85/89 Sr 2
Page 101 and 102: 6.2. PREPARATION AND BIOEVALUATION
Page 103 and 104: (a) (b) (c) FIG. 6.5. PD-10 column
Page 105 and 106: FIG. 6.7. SDS PAGE pattern of ritux
Page 107 and 108: FIG. 6.10. HPLC pattern of pure 90
Page 109 and 110: FIG. 6.13. Cell binding studies wit
Page 111 and 112: 6.2.1.6. Conclusion The procedure f
Page 113 and 114: FIG. 6.17. Elution profile of 90 Y
Page 115 and 116: form NADH, which, in turn, causes t
Page 117 and 118: FIG. 6.19. In vivo distribution pat
Page 119 and 120: ACKNOWLEDGEMENTS The authors of thi
Page 121 and 122: Chapter 7 DEVELOPMENT OF THERAPEUTI
Page 123 and 124: the residual breast tissue becoming
Page 125 and 126: 7.2.5.2. Automatic procedure The la
Page 127 and 128: FIG. 7.2. RCP values of 90 Y r-BHD
Page 129 and 130: FIG. 7.3. Pyrogen test shows result
Page 131 and 132: to avidin at the 1:4 avidin:r-BHD m
Page 133 and 134: [7.9] SU, F.M., GUSTAVSON, L.M., AX
Page 135 and 136: 8.1. INTRODUCTION In past years, th
Page 137 and 138: (a) FIG. 8.1. (a) Schematic illustr
Page 139 and 140: Preliminary synthesis of the biotin
Page 141 and 142: (a) (b) FIG. 8.4. (a) PEGylated and
Page 143 and 144: TABLE 8.2. BIODISTRIBUTION IN RATS
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A specific binding to avidin was ev
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[8.13] BOSCHI, A., DUATTI, A., UCCE
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90 Y solution obtained from a 90 Sr
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From each fraction, a ~1 g aliquot
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FIG. 9.2. Relationship between 90 S
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with 188 Re obtained from the 188 W
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9.3.2. Labelling of DPA ale DPA ale
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FIG. 9.8. TLC radiochromatogram of
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(-) 188 Re(CO) 3 (+) (-) 99m Tc(CO)
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the HSA solution containing sodium
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TABLE 9.3. RESULTS OF 99m Tc LABELL
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9.4.4. Yttrium-90 and 177 Lu labell
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FIG. 9.14. In vitro stability of 90
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(a) (b) (c) (d) (e) (f) (g) (h) (i)
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TABLE 9.8. YTTRIUM-90 CITRATE COLLO
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(a) (b) FIG. 9.17. Grain size distr
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TABLE 9.10. BIODISTRIBUTION AFTER A
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FIG. 9.19. Structure of DOTA biotin
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[9.8] WESTERA, G., GADZE, A., HORST
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Chapter 10 DEVELOPMENT, PREPARATION
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acidic pH) and the vial heated for
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10.2.2.1. Materials and methods (a)
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Using a semiquantitative method, th
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FIG. 10.3. Whole body, SPECT and ta
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TABLE 10.4. ORGAN DISTRIBUTION STUD
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was assessed by measuring the relea
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—— Biological studies: The whol
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or liver) (see Fig. 10.7). The resu
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(b) Results and discussion Healthy
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and the pellet (particles of HA lab
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FIG. 10.11. Organ distribution stud
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The procedure was as follows: —
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TABLE 10.5. INFLUENCE OF CHEMICAL I
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analysed using ICP OES was within t
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suggested for separation of pure 86
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adionuclidic purity of the 90 Y sol
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FIG. 10.16. (a) Strontium-90/yttriu
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[10.5] DJOKIĆ, D.J., JANKOVIĆ, D.
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Yttrium-90 is one of the radionucli
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(a) (b) (c) The generator was prepa
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—— Development of EPC: The EPC
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FIG. 11.4. Elution curve of 90 Sr e
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11.4. YTTRIUM-90 MAbs The use of th
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FIG. 11.6. RCP measured using ITLC
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FIG. 11.9. Biodistribution of 90 Y
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11.5. YTTRIUM-90 EDTMP Bone metasta
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FIG. 11.14. Electrophoresis of 90 Y
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FIG. 11.15. Particle size distribut
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11.7. CONCLUSION During this CRP, a
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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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