ZA200507983B - Thorium-227 for use in radiotherapy of soft tissue disease - Google Patents
Thorium-227 for use in radiotherapy of soft tissue disease Download PDFInfo
- Publication number
- ZA200507983B ZA200507983B ZA200507983A ZA200507983A ZA200507983B ZA 200507983 B ZA200507983 B ZA 200507983B ZA 200507983 A ZA200507983 A ZA 200507983A ZA 200507983 A ZA200507983 A ZA 200507983A ZA 200507983 B ZA200507983 B ZA 200507983B
- Authority
- ZA
- South Africa
- Prior art keywords
- thorium
- soft tissue
- complexing agent
- complex
- radium
- Prior art date
Links
- ZSLUVFAKFWKJRC-FTXFMUIASA-N thorium-227 Chemical compound [227Th] ZSLUVFAKFWKJRC-FTXFMUIASA-N 0.000 title claims description 63
- 208000016247 Soft tissue disease Diseases 0.000 title claims description 15
- 238000001959 radiotherapy Methods 0.000 title description 4
- 238000000034 method Methods 0.000 claims description 48
- 230000008685 targeting Effects 0.000 claims description 48
- 210000004872 soft tissue Anatomy 0.000 claims description 44
- 229910052776 Thorium Inorganic materials 0.000 claims description 36
- 239000008139 complexing agent Substances 0.000 claims description 32
- 238000011282 treatment Methods 0.000 claims description 30
- 201000010099 disease Diseases 0.000 claims description 29
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 29
- HCWPIIXVSYCSAN-OIOBTWANSA-N radium-223 Chemical compound [223Ra] HCWPIIXVSYCSAN-OIOBTWANSA-N 0.000 claims description 28
- 229960005562 radium-223 Drugs 0.000 claims description 27
- 230000000694 effects Effects 0.000 claims description 21
- 206010028980 Neoplasm Diseases 0.000 claims description 20
- 238000001727 in vivo Methods 0.000 claims description 20
- 210000001519 tissue Anatomy 0.000 claims description 15
- 231100001180 nonmyelotoxic Toxicity 0.000 claims description 14
- 230000037396 body weight Effects 0.000 claims description 12
- 150000001875 compounds Chemical class 0.000 claims description 10
- 230000000536 complexating effect Effects 0.000 claims description 7
- 230000003211 malignant effect Effects 0.000 claims description 7
- 239000000203 mixture Substances 0.000 claims description 7
- WDLRUFUQRNWCPK-UHFFFAOYSA-N Tetraxetan Chemical class OC(=O)CN1CCN(CC(O)=O)CCN(CC(O)=O)CCN(CC(O)=O)CC1 WDLRUFUQRNWCPK-UHFFFAOYSA-N 0.000 claims description 6
- 102000008394 Immunoglobulin Fragments Human genes 0.000 claims description 5
- 108010021625 Immunoglobulin Fragments Proteins 0.000 claims description 5
- 206010025323 Lymphomas Diseases 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- -1 thorium ions Chemical class 0.000 claims description 5
- 238000002512 chemotherapy Methods 0.000 claims description 4
- 238000010438 heat treatment Methods 0.000 claims description 4
- 239000003446 ligand Substances 0.000 claims description 4
- 238000002560 therapeutic procedure Methods 0.000 claims description 4
- 201000009030 Carcinoma Diseases 0.000 claims description 3
- 206010039491 Sarcoma Diseases 0.000 claims description 3
- 238000001356 surgical procedure Methods 0.000 claims description 3
- 241000282465 Canis Species 0.000 claims description 2
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 238000002710 external beam radiation therapy Methods 0.000 claims description 2
- 201000000050 myeloid neoplasm Diseases 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 238000002660 stem cell treatment Methods 0.000 claims description 2
- 238000011277 treatment modality Methods 0.000 claims description 2
- ZSLUVFAKFWKJRC-IGMARMGPSA-N 232Th Chemical compound [232Th] ZSLUVFAKFWKJRC-IGMARMGPSA-N 0.000 description 32
- 210000004027 cell Anatomy 0.000 description 29
- 230000001225 therapeutic effect Effects 0.000 description 22
- 239000002738 chelating agent Substances 0.000 description 19
- 230000014759 maintenance of location Effects 0.000 description 17
- 229910052705 radium Inorganic materials 0.000 description 17
- 230000000717 retained effect Effects 0.000 description 15
- HCWPIIXVSYCSAN-UHFFFAOYSA-N radium atom Chemical compound [Ra] HCWPIIXVSYCSAN-UHFFFAOYSA-N 0.000 description 13
- 239000000243 solution Substances 0.000 description 12
- 241000282412 Homo Species 0.000 description 10
- 210000004369 blood Anatomy 0.000 description 10
- 239000008280 blood Substances 0.000 description 10
- 230000005855 radiation Effects 0.000 description 10
- 239000000047 product Substances 0.000 description 9
- 102000004169 proteins and genes Human genes 0.000 description 9
- 108090000623 proteins and genes Proteins 0.000 description 9
- 230000002285 radioactive effect Effects 0.000 description 9
- 231100000419 toxicity Toxicity 0.000 description 9
- 230000001988 toxicity Effects 0.000 description 9
- 238000002347 injection Methods 0.000 description 8
- 239000007924 injection Substances 0.000 description 8
- 210000000440 neutrophil Anatomy 0.000 description 8
- 239000002245 particle Substances 0.000 description 8
- 241000282472 Canis lupus familiaris Species 0.000 description 7
- 229960004641 rituximab Drugs 0.000 description 7
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 6
- 239000000427 antigen Substances 0.000 description 6
- 108091007433 antigens Proteins 0.000 description 6
- 102000036639 antigens Human genes 0.000 description 6
- 230000001588 bifunctional effect Effects 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 239000002502 liposome Substances 0.000 description 6
- 239000011159 matrix material Substances 0.000 description 6
- QPCDCPDFJACHGM-UHFFFAOYSA-N N,N-bis{2-[bis(carboxymethyl)amino]ethyl}glycine Chemical class OC(=O)CN(CC(O)=O)CCN(CC(=O)O)CCN(CC(O)=O)CC(O)=O QPCDCPDFJACHGM-UHFFFAOYSA-N 0.000 description 5
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 230000006378 damage Effects 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 239000012634 fragment Substances 0.000 description 5
- 238000002372 labelling Methods 0.000 description 5
- 231100000518 lethal Toxicity 0.000 description 5
- 230000001665 lethal effect Effects 0.000 description 5
- 229960003330 pentetic acid Drugs 0.000 description 5
- 229940051022 radioimmunoconjugate Drugs 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 231100000331 toxic Toxicity 0.000 description 5
- 230000002588 toxic effect Effects 0.000 description 5
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 4
- 208000026310 Breast neoplasm Diseases 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 206010060862 Prostate cancer Diseases 0.000 description 4
- 210000000988 bone and bone Anatomy 0.000 description 4
- 239000013522 chelant Substances 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 230000008030 elimination Effects 0.000 description 4
- 238000003379 elimination reaction Methods 0.000 description 4
- 231100000226 haematotoxicity Toxicity 0.000 description 4
- 229940088597 hormone Drugs 0.000 description 4
- 239000005556 hormone Substances 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 229910052751 metal Inorganic materials 0.000 description 4
- 239000002184 metal Substances 0.000 description 4
- 108090000765 processed proteins & peptides Proteins 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 238000011287 therapeutic dose Methods 0.000 description 4
- 108090001008 Avidin Proteins 0.000 description 3
- 206010006187 Breast cancer Diseases 0.000 description 3
- 239000002211 L-ascorbic acid Substances 0.000 description 3
- 235000000069 L-ascorbic acid Nutrition 0.000 description 3
- 206010027476 Metastases Diseases 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 150000001218 Thorium Chemical class 0.000 description 3
- QQINRWTZWGJFDB-YPZZEJLDSA-N actinium-225 Chemical compound [225Ac] QQINRWTZWGJFDB-YPZZEJLDSA-N 0.000 description 3
- 230000002411 adverse Effects 0.000 description 3
- 229960005070 ascorbic acid Drugs 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 210000001185 bone marrow Anatomy 0.000 description 3
- 230000022534 cell killing Effects 0.000 description 3
- 125000004122 cyclic group Chemical group 0.000 description 3
- 229940014144 folate Drugs 0.000 description 3
- 239000011724 folic acid Substances 0.000 description 3
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 3
- 235000019152 folic acid Nutrition 0.000 description 3
- 229940127121 immunoconjugate Drugs 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 125000005647 linker group Chemical group 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 206010061289 metastatic neoplasm Diseases 0.000 description 3
- 102000004196 processed proteins & peptides Human genes 0.000 description 3
- 239000012217 radiopharmaceutical Substances 0.000 description 3
- 229940121896 radiopharmaceutical Drugs 0.000 description 3
- 230000002799 radiopharmaceutical effect Effects 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 210000004881 tumor cell Anatomy 0.000 description 3
- UDOPJKHABYSVIX-UHFFFAOYSA-N 2-[4,7,10-tris(carboxymethyl)-6-[(4-isothiocyanatophenyl)methyl]-1,4,7,10-tetrazacyclododec-1-yl]acetic acid Chemical compound C1N(CC(O)=O)CCN(CC(=O)O)CCN(CC(O)=O)CCN(CC(O)=O)C1CC1=CC=C(N=C=S)C=C1 UDOPJKHABYSVIX-UHFFFAOYSA-N 0.000 description 2
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 2
- 239000005695 Ammonium acetate Substances 0.000 description 2
- 206010065553 Bone marrow failure Diseases 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 241001637516 Polygonia c-album Species 0.000 description 2
- 229920005654 Sephadex Polymers 0.000 description 2
- 239000012507 Sephadex™ Substances 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 2
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 2
- 229940125666 actinium-225 Drugs 0.000 description 2
- 229940043376 ammonium acetate Drugs 0.000 description 2
- 235000019257 ammonium acetate Nutrition 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 229960002685 biotin Drugs 0.000 description 2
- 235000020958 biotin Nutrition 0.000 description 2
- 239000011616 biotin Substances 0.000 description 2
- 210000001772 blood platelet Anatomy 0.000 description 2
- 210000000481 breast Anatomy 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 231100000135 cytotoxicity Toxicity 0.000 description 2
- 230000003013 cytotoxicity Effects 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 238000001730 gamma-ray spectroscopy Methods 0.000 description 2
- 230000002489 hematologic effect Effects 0.000 description 2
- 239000012216 imaging agent Substances 0.000 description 2
- 210000000265 leukocyte Anatomy 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000001394 metastastic effect Effects 0.000 description 2
- 208000037819 metastatic cancer Diseases 0.000 description 2
- 208000011575 metastatic malignant neoplasm Diseases 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 2
- 230000005258 radioactive decay Effects 0.000 description 2
- HCWPIIXVSYCSAN-YPZZEJLDSA-N radium-224 Chemical compound [224Ra] HCWPIIXVSYCSAN-YPZZEJLDSA-N 0.000 description 2
- 229910052704 radon Inorganic materials 0.000 description 2
- SYUHGPGVQRZVTB-UHFFFAOYSA-N radon atom Chemical compound [Rn] SYUHGPGVQRZVTB-UHFFFAOYSA-N 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 102220162701 rs201262353 Human genes 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 230000009870 specific binding Effects 0.000 description 2
- 210000000130 stem cell Anatomy 0.000 description 2
- 230000003637 steroidlike Effects 0.000 description 2
- MRYQZMHVZZSQRT-UHFFFAOYSA-M tetramethylazanium;acetate Chemical compound CC([O-])=O.C[N+](C)(C)C MRYQZMHVZZSQRT-UHFFFAOYSA-M 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- KZLVRAKJPTYSTD-UHFFFAOYSA-N 2-[(4-isothiocyanatophenyl)methyl]-1,4,7,10-tetrazacyclododecane Chemical compound C1=CC(N=C=S)=CC=C1CC1NCCNCCNCCNC1 KZLVRAKJPTYSTD-UHFFFAOYSA-N 0.000 description 1
- VAOYPHGXHKUTHC-KRWDZBQOSA-N 2-[2-[bis(carboxymethyl)amino]ethyl-[(2s)-2-[bis(carboxymethyl)amino]-3-(4-isothiocyanatophenyl)propyl]amino]acetic acid Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(=O)O)C[C@@H](N(CC(O)=O)CC(O)=O)CC1=CC=C(N=C=S)C=C1 VAOYPHGXHKUTHC-KRWDZBQOSA-N 0.000 description 1
- STNZNCWQNMGRIM-UHFFFAOYSA-N 2-benzyl-1,4,7,10-tetrakis-(4-methylphenyl)sulfonyl-1,4,7,10-tetrazacyclododecane Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N1CCN(S(=O)(=O)C=2C=CC(C)=CC=2)CC(CC=2C=CC=CC=2)N(S(=O)(=O)C=2C=CC(C)=CC=2)CCN(S(=O)(=O)C=2C=CC(C)=CC=2)CC1 STNZNCWQNMGRIM-UHFFFAOYSA-N 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 206010002556 Ankylosing Spondylitis Diseases 0.000 description 1
- 108091023037 Aptamer Proteins 0.000 description 1
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 description 1
- 206010005949 Bone cancer Diseases 0.000 description 1
- 206010051779 Bone marrow toxicity Diseases 0.000 description 1
- 208000018084 Bone neoplasm Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 208000001640 Fibromyalgia Diseases 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 description 1
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 1
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 1
- 206010027457 Metastases to liver Diseases 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 208000003788 Neoplasm Micrometastasis Diseases 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical group [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 102000015636 Oligopeptides Human genes 0.000 description 1
- 108010038807 Oligopeptides Proteins 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 208000019155 Radiation injury Diseases 0.000 description 1
- 208000000453 Skin Neoplasms Diseases 0.000 description 1
- 208000032383 Soft tissue cancer Diseases 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- 102000007000 Tenascin Human genes 0.000 description 1
- 108010008125 Tenascin Proteins 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- QQINRWTZWGJFDB-IGMARMGPSA-N actinium-227 Chemical compound [227Ac] QQINRWTZWGJFDB-IGMARMGPSA-N 0.000 description 1
- 230000005262 alpha decay Effects 0.000 description 1
- LBDSXVIYZYSRII-IGMARMGPSA-N alpha-particle Chemical compound [4He+2] LBDSXVIYZYSRII-IGMARMGPSA-N 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 238000005349 anion exchange Methods 0.000 description 1
- 239000003957 anion exchange resin Substances 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 229910052789 astatine Inorganic materials 0.000 description 1
- RYXHOMYVWAEKHL-UHFFFAOYSA-N astatine atom Chemical compound [At] RYXHOMYVWAEKHL-UHFFFAOYSA-N 0.000 description 1
- RYXHOMYVWAEKHL-OUBTZVSYSA-N astatine-211 Chemical compound [211At] RYXHOMYVWAEKHL-OUBTZVSYSA-N 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000027455 binding Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- JCXGWMGPZLAOME-RNFDNDRNSA-N bismuth-213 Chemical compound [213Bi] JCXGWMGPZLAOME-RNFDNDRNSA-N 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 238000004820 blood count Methods 0.000 description 1
- 231100000366 bone marrow toxicity Toxicity 0.000 description 1
- 210000002805 bone matrix Anatomy 0.000 description 1
- 150000001642 boronic acid derivatives Chemical class 0.000 description 1
- 239000012888 bovine serum Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 150000001669 calcium Chemical class 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 125000004181 carboxyalkyl group Chemical group 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 210000003679 cervix uteri Anatomy 0.000 description 1
- 150000004697 chelate complex Chemical class 0.000 description 1
- 230000009920 chelation Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- CDMADVZSLOHIFP-UHFFFAOYSA-N disodium;3,7-dioxido-2,4,6,8,9-pentaoxa-1,3,5,7-tetraborabicyclo[3.3.1]nonane;decahydrate Chemical compound O.O.O.O.O.O.O.O.O.O.[Na+].[Na+].O1B([O-])OB2OB([O-])OB1O2 CDMADVZSLOHIFP-UHFFFAOYSA-N 0.000 description 1
- 231100000371 dose-limiting toxicity Toxicity 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000001210 effect on neutrophils Effects 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 229940011871 estrogen Drugs 0.000 description 1
- 239000000262 estrogen Substances 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 150000002224 folic acids Chemical class 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 230000005251 gamma ray Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 150000002371 helium Chemical class 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 238000001794 hormone therapy Methods 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 230000002390 hyperplastic effect Effects 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 231100000636 lethal dose Toxicity 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 238000013160 medical therapy Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 238000006263 metalation reaction Methods 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 238000009126 molecular therapy Methods 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 230000001613 neoplastic effect Effects 0.000 description 1
- 208000004235 neutropenia Diseases 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 229910052756 noble gas Inorganic materials 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 238000002727 particle therapy Methods 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 231100000683 possible toxicity Toxicity 0.000 description 1
- 208000037920 primary disease Diseases 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 230000002250 progressing effect Effects 0.000 description 1
- 208000037821 progressive disease Diseases 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 201000001514 prostate carcinoma Diseases 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000002510 pyrogen Substances 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000010339 sodium tetraborate Nutrition 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 231100000901 systemic toxic effect Toxicity 0.000 description 1
- 231100000057 systemic toxicity Toxicity 0.000 description 1
- 238000011361 targeted radionuclide therapy Methods 0.000 description 1
- 229960003604 testosterone Drugs 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 229940124598 therapeutic candidate Drugs 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
- A61K51/10—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody
- A61K51/1093—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody conjugates with carriers being antibodies
- A61K51/1096—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody conjugates with carriers being antibodies radioimmunotoxins, i.e. conjugates being structurally as defined in A61K51/1093, and including a radioactive nucleus for use in radiotherapeutic applications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
- A61K51/10—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody
- A61K51/1027—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody against receptors, cell-surface antigens or cell-surface determinants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N5/00—Radiation therapy
- A61N5/10—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
- A61N5/1001—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy using radiation sources introduced into or applied onto the body; brachytherapy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Optics & Photonics (AREA)
- Physics & Mathematics (AREA)
- Immunology (AREA)
- Biomedical Technology (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Radiology & Medical Imaging (AREA)
- Pathology (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Radiation-Therapy Devices (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0308731.9A GB0308731D0 (en) | 2003-04-15 | 2003-04-15 | Method of radiotherapy |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200507983B true ZA200507983B (en) | 2007-03-28 |
Family
ID=35385222
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200507983A ZA200507983B (en) | 2003-04-15 | 2004-04-15 | Thorium-227 for use in radiotherapy of soft tissue disease |
Country Status (19)
| Country | Link |
|---|---|
| EP (1) | EP1617876B1 (fr) |
| JP (2) | JP5006032B2 (fr) |
| KR (2) | KR101274867B1 (fr) |
| CN (1) | CN100586484C (fr) |
| AU (1) | AU2004229218B2 (fr) |
| BR (1) | BRPI0409387B8 (fr) |
| CA (1) | CA2522148C (fr) |
| CY (1) | CY1115407T1 (fr) |
| DK (1) | DK1617876T3 (fr) |
| EA (1) | EA008195B1 (fr) |
| ES (1) | ES2486845T3 (fr) |
| HK (1) | HK1094150A1 (fr) |
| IL (1) | IL171148A (fr) |
| MX (1) | MXPA05010804A (fr) |
| NO (1) | NO332931B1 (fr) |
| NZ (3) | NZ543044A (fr) |
| PL (1) | PL1617876T3 (fr) |
| PT (1) | PT1617876E (fr) |
| ZA (1) | ZA200507983B (fr) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ543044A (en) * | 2003-04-15 | 2010-04-30 | Algeta As | Thorium-227 for use in radiotherapy of soft tissue disease |
| GB201002508D0 (en) * | 2010-02-12 | 2010-03-31 | Algeta As | Product |
| GB201007354D0 (en) * | 2010-04-30 | 2010-06-16 | Algeta Asa | Method |
| GB201105298D0 (en) * | 2011-03-29 | 2011-05-11 | Algeta Asa | Pharmaceutical preparation |
| GB201600153D0 (en) * | 2016-01-05 | 2016-02-17 | Bayer As | Isotope preparation method |
| GB201600154D0 (en) * | 2016-01-05 | 2016-02-17 | Bayer As | Isotope preparation method |
| ES2952744T3 (es) | 2016-12-15 | 2023-11-03 | Nestle Sa | Composiciones y procedimientos que modulan los glóbulos blancos o los neutrófilos en un animal de compañía |
| FR3088769B1 (fr) * | 2018-11-15 | 2020-12-25 | Orano Med | Procede de preparation d'au moins un generateur a haute teneur en radium-228 |
| RU2767567C1 (ru) * | 2020-10-27 | 2022-03-17 | Станислав Анатольевич Дороватовский | Комплексные соединения, содержащие в своем составе радионуклид 227Th, а также бисфосфонатный фрагмент, способы их получения, а также потенциальное применение в качестве действующего вещества в составе остеотропного радиофармацевтического лекарственного препарата |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2053196T3 (es) * | 1989-06-19 | 1994-07-16 | Akzo Nv | Metodo para la produccion de un radioinmunoconjugado. |
| WO1993020852A2 (fr) * | 1992-04-13 | 1993-10-28 | The Dow Chemical Company | Agents de chelation macrocycliques, leurs chelates et conjugues |
| MY133346A (en) * | 1999-03-01 | 2007-11-30 | Biogen Inc | Kit for radiolabeling ligands with yttrium-90 |
| NO314537B1 (no) * | 1999-12-06 | 2003-04-07 | Anticancer Therapeutic Inv Sa | Reseptorbindende konjugater |
| NO312708B1 (no) * | 2000-02-21 | 2002-06-24 | Anticancer Therapeutic Inv Sa | Radioaktive liposomer til terapi |
| EP1227849A2 (fr) * | 2000-02-25 | 2002-08-07 | Dangshe Ma | Complexes et conjugat d'actinium-225 pour radio-immunotherapie |
| NO313180B1 (no) * | 2000-07-04 | 2002-08-26 | Anticancer Therapeutic Inv Sa | Bensökende alfapartikkel emitterende radiofarmasöytika |
| ITMI20022411A1 (it) * | 2002-11-14 | 2004-05-15 | Bracco Imaging Spa | Agenti per la diagnosi e la terapia di tumori che espongono sulla superficie delle cellule proteine alterate. |
| NZ543044A (en) * | 2003-04-15 | 2010-04-30 | Algeta As | Thorium-227 for use in radiotherapy of soft tissue disease |
-
2004
- 2004-04-15 NZ NZ543044A patent/NZ543044A/en unknown
- 2004-04-15 ZA ZA200507983A patent/ZA200507983B/en unknown
- 2004-04-15 JP JP2006506137A patent/JP5006032B2/ja not_active Expired - Lifetime
- 2004-04-15 EP EP04727587.0A patent/EP1617876B1/fr not_active Expired - Lifetime
- 2004-04-15 PL PL04727587T patent/PL1617876T3/pl unknown
- 2004-04-15 CN CN200480016329A patent/CN100586484C/zh not_active Expired - Lifetime
- 2004-04-15 NZ NZ606996A patent/NZ606996A/en not_active IP Right Cessation
- 2004-04-15 AU AU2004229218A patent/AU2004229218B2/en not_active Expired
- 2004-04-15 KR KR1020117003862A patent/KR101274867B1/ko active IP Right Grant
- 2004-04-15 KR KR1020057019497A patent/KR20060015507A/ko not_active Application Discontinuation
- 2004-04-15 ES ES04727587.0T patent/ES2486845T3/es not_active Expired - Lifetime
- 2004-04-15 DK DK04727587.0T patent/DK1617876T3/da active
- 2004-04-15 PT PT47275870T patent/PT1617876E/pt unknown
- 2004-04-15 NZ NZ595758A patent/NZ595758A/xx not_active IP Right Cessation
- 2004-04-15 MX MXPA05010804A patent/MXPA05010804A/es active IP Right Grant
- 2004-04-15 EA EA200501456A patent/EA008195B1/ru not_active IP Right Cessation
- 2004-04-15 BR BRPI0409387A patent/BRPI0409387B8/pt active IP Right Grant
- 2004-04-15 CA CA2522148A patent/CA2522148C/fr not_active Expired - Lifetime
-
2005
- 2005-09-28 IL IL171148A patent/IL171148A/en active IP Right Grant
- 2005-11-15 NO NO20055390A patent/NO332931B1/no unknown
-
2007
- 2007-01-19 HK HK07100706.8A patent/HK1094150A1/xx not_active IP Right Cessation
-
2011
- 2011-12-02 JP JP2011265169A patent/JP5468597B2/ja not_active Expired - Lifetime
-
2014
- 2014-07-28 CY CY20141100569T patent/CY1115407T1/el unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20140235924A1 (en) | Method of radiotherapy | |
| JP5468597B2 (ja) | 軟組織疾患の放射線治療におけるトリウム−２２７を用いた医薬組成物、複合体及びその調製方法、並びにキット | |
| AU2005259258B2 (en) | Radionuclides for medical use | |
| Dadachova | Cancer therapy with alpha-emitters labeled peptides | |
| Hatcher-Lamarre et al. | Alpha emitting nuclides for targeted therapy | |
| Ferrier et al. | An appendix of radionuclides used in targeted alpha therapy | |
| US20060228297A1 (en) | Thorium-227 for use in radiotherapy of soft tissue disease | |
| Audicio et al. | [177Lu] DOTA-anti-CD20: labeling and pre-clinical studies | |
| JP2019059747A (ja) | 有利な特性を有する放射性医薬溶液 | |
| US7794691B2 (en) | Radionuclides for medical use | |
| Zhang et al. | Alpha‐emitters and targeted alpha therapy in cancer treatment | |
| US20020082389A1 (en) | Method and means for site directed therapy | |
| Vallabhajosula | Radiopharmaceuticals for therapy | |
| Bailey | Advancing targeting radiopharmaceuticals for theranostic applications | |
| Ma | Trithiol Ligand Development for Radioarsenic and Radioantimony toward Potential Theranostic Radiopharmaceutical Agents | |
| Cieszykowska et al. | Radiometals in Molecular Imaging and Therapy | |
| Fonslet | Production and utilization of unconventional radiometals for advanced diagnostics and therapy | |
| Barrio et al. | Dosimetric studies of anti-CD20 labeled with therapeutic radionuclides at IPEN/CNEN-SP | |
| Ramdahl et al. | Targeted alpha emitters in tumor therapy | |
| Frenvik | Development of separation technology for the removal of radium-223 from targeted thorium conjugate formulations. |