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Title:
RADIODENSE COMPOSITIONS
Document Type and Number:
WIPO Patent Application WO/2000/025829
Kind Code:
A2
Abstract:
The invention relates to radiodense compositions for use in methods of radiation treatment of target tissues, such as tumors, the radiodense compositions include a particulate or polymeric contrast agent that has a dwell time within the target tissue of at least one hour.

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Inventors:
MCINTIRE GREGORY L (US)
BACON EDWARD R (US)
ILLIG KATHLEEN J (US)
WOLF GERALD L (US)
Application Number:
PCT/US1999/025529
Publication Date:
May 11, 2000
Filing Date:
October 29, 1999
Export Citation:
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Assignee:
GEN HOSPITAL CORP (US)
NYCOMED IMAGING AS (NO)
MCINTIRE GREGORY L (US)
BACON EDWARD R (US)
ILLIG KATHLEEN J (US)
WOLF GERALD L (US)
International Classes:
A61K9/127; A61K31/167; A61K31/235; A61K33/06; A61K33/18; A61K33/22; A61K33/24; A61K33/26; A61K33/32; A61K33/38; A61K41/00; A61K45/00; A61K49/04; A61K51/00; A61N5/10; A61P35/00; C08G73/02; C08K3/08; C08K5/00; C08L79/02; (IPC1-7): A61K49/00
Domestic Patent References:
WO1998047532A11998-10-29
WO1994027644A11994-12-08
WO2000025819A12000-05-11
WO2000043045A12000-07-27
Foreign References:
US5665330A1997-09-09
US5008907A1991-04-16
Other References:
DATABASE MEDLINE [Online] US NATIONAL LIBRARY OF MEDICINE (NLM), BETHESDA, MD, US; SANTOS MELLO R ET AL: "Radiation dose enhancement in tumors with iodine." retrieved from STN Database accession no. 83191891 XP002134800 & MEDICAL PHYSICS, (1983 JAN-FEB) 10 (1) 75-8.,
Attorney, Agent or Firm:
Fasse, Peter J. (MA, US)
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Claims:
Claims
1. A radiodense composition for use in a method of radiation treatment of a target tissue in an animate subject, the radiodense composition comprising a particulate or polymeric contrast agent that has a dwell time within the target tissue of at least one hour, and wherein the radiodense composition is administered directly into the target tissue, and the target tissue is thereafter exposed to radiation.
2. The composition of claim 1, wherein the composition comprises a radiationinduced cytotoxic radiationemitting agent.
3. The composition of claim 1, wherein the composition comprises a cytotoxic radiation dose enhancing agent.
4. The composition of claim 1, wherein the radiodense composition comprises iohexol, iopamidol, ioversol, ioxilan, iomeprol, or iodixanol.
5. The composition of claim 1, wherein the radiodense composition comprises iodine, barium, bismuth, boron, bromine, calcium, gold, silver, iron, manganese, nickel, gadolinium, dysprosium, tungsten, tantalum, stainless steel, or nitinol, or a combination of any one or more of the above.
6. The composition of claim 1, wherein the radiodense composition comprises a radiodense material present within a small, lipid soluble molecule.
7. The composition of claim 1, wherein the radiodense composition has a dwell time within the target tissue of at least 5 hours.
8. The composition of claim 1, wherein the radiodense composition has a dwell time within the target tissue of at least 24 hours.
9. The composition of claim 1, wherein the radiodense composition is about 10 nanometers to 100 microns in size.
10. The composition of claim 1, wherein the radiodense composition comprises NI244, NI212, or a liposome comprising iohexol.
11. The composition of claim 1, wherein the composition further comprises a soluble Xray dense material.
12. The composition of claim 1, wherein the target tissue is a tumor.
13. The use of a radiodense composition of claim 1 in the manufacture of a therapeutic agent for use in a method of radiation therapy of a target tissue.
14. A linear or branched polymer comprising alternating chelant and iodinated aromatic moieties, the chelant moieties comprising the residue of a linear polyaminocarboxylic acid or derivative thereof capable of complexing a metal ion, or a salt or chelate of the polymer.
15. A polymeric composition comprising formula I: wherein X is O, NH, NR, (CH2) mNR, or CO2 (CH2) mNR; Z is CO2H, CO2R, CH2CO2R, CONR2, OH, OR, or a solubility enhancing group; R is independently hydrogen or an alkyl or aryl group, optionally substituted by one or more hydroxy, alkoxy, amine, or carboxy groups; n is a positive integer; and m is zero or 1 to 8.
16. The composition of claim 15, wherein the composition is a polyaminocarboxylic acidbased polymer.
17. The composition of claim 15, wherein the solubility of the compound is enhanced by varying the nature of group Z.
18. The composition of claim 15, wherein X is O or NH.
19. The composition of claim 15, wherein Z is CO2H or OH.
20. The composition of claim 15, wherein Z is a poly (alkylene oxide) moiety.
21. The composition of claim 15, wherein n is 1 to 300.
22. The composition of claim 15, wherein m is 0 to 4.
23. A method for preparing a polymeric composition, the method comprising reacting one or more monochelant compounds having at least one reactive functional group with one or more iodinated aromatic moieties having at least one functional group capable of reacting with reactive groups of said monochelants.
24. The method of claim 23, wherein the iodinated aromatic moieties each comprise at least two functional groups.
25. The method of claim 23, wherein the method is used to prepare the polymeric composition of claim 7.
26. A method of preparing a polymeric composition, the method comprising (a) converting a polyaminocarboxylate monochelant into an activated polyaminocarboxylate compound containing one or more reactive groups; and (b) forming an amide or ester linkage between the activated polyaminocarboxylate compound and an aromatic iodinated compound to form the polymeric composition.
27. The method of claim 26, further comprising (c) repeating steps (a) and (b) with the product of step (b) to produce a higher polymer.
28. The method of claim 26, further comprising protecting one or more of the reactive groups in the activated polyaminocarboxylate compound during the step of forming the linkage between the compounds.
29. A method of claim 26, wherein the reactive groups in the activated polyaminocarboxylate compound comprise an amide or anhydride.
30. A method of claim 26, wherein the reactive groups in the activated polyaminocarboxylate compound comprise an activated carboxyl group.
31. The method of claim 26, wherein the method is used to prepare the polymeric composition of claim 8.
32. A method for preparing a polymeric composition, the method comprising reacting a compound of formula II: with a compound of formula III: Z is CO2H, CO2R, CH2CO2R, CONR2, OH, OR, or a solubility enhancing group; and Y is OH, NH2, or CH2NH2).
Description:
INTERNATIONALSEARCHREPORT Inte onal ApplicationNo PCT/US99/25529 C.(Continuation)DOCUMENTSCONSIDEREDTOBERELEVANT Category° Citation ofdocument,withindication,whereappropriate,oftherelevantpass agesRelevanttoclaimNo. DATABASE MEDLINE'Online!1-13 USNATIONALLIBRARYOFMEDICINE(NLM), BETHESDA,MD,US; SANTOSMELLORETAL:"Radiationdose enhancementintumorswithiodine." retrievedfromSTN Databaseaccessionno.83191891 XP002134800 abstract &MEDICALPHYSICS,(1983JAN-FEB)10(1) 75-8., XWO9427644A(ANELLIPIERLUCIO;HAEN14-32 CHRISTOPHDE(IT);DIBRASPA(IT);FEDELI) 8December1994(1994-12-08) page17,line15-line30;claims page20,line20-page21,line9 page13,line13-line27;claims1,3,4,6 EWO0025819A(NYCOMEDIMAGINGAS;GEN14 HOSPITALCORP(US);WOLFGERALDL(US); BA)11May2000(2000-05-11) claims EWO0043045A(PHOTOGENINC)14 27July2000(2000-07-27) claims1,28,30,31 3 II, ternational applicationNo. INTERNATIONALSEARCHREPORTPCT/US99/25529 Box IObservationswherecertainclaimswerefoundunsearchable(Continu ationofitem1offirstsheet) ThisInternationalSearchReporthasnotbeenestablishedinrespecto fcertainclaimsunderArticle17(2)(a)forthefollowingreasons: 1.ClaimsNos.: becausetheyrelatetosubjectmatternotrequiredtobesearchedbythi sAuthority,namely: 2.F-IClaimsNos.: becausetheyrelatetopartsoftheIntemationalApplicationthatdono tcomplywiththeprescribedrequirementstosuch anextentthatnomeaningfulInternationalSearchcanbecarriedout,s pecifically: 3.ngClaimsNos.: becausetheyaredependentclaimsandarenotdraftedinaccordancewit hthesecondandthirdsentencesofRule6.4(a). Box11Observationswhereunityofinventionislacking(Continuation ofitem2offirstsheet) ThisIntemationalSearchingAuthorityfoundmultipleinventionsint hisinternationalapplication,asfollows: seeadditionalsheet 1.As allrequiredadditionalsearchfeesweretimelypaidbytheapplicant, thisIntemationalSearchReportcoversall searchableclaims. 2.As allsearchableclaimscouldbesearchedwithouteffortjustifyingana dditionalfee,thisAuthoritydidnotinvitepayment ofanyadditionalfee. 3.Asonlysomeoftherequiredadditionalsearchfeesweretimelypaidb ytheapplicant,thisinternationalSearchReport conversonlythoseclaimsforwhichfeeswerepaid,specificallyclaim sNos.: 4.njNorequiredadditionalsearchfeesweretimelypaidbytheapplica nt.Consequently,thisInternationalSearchReportis restrictedtotheinventionfirstmentionedintheclaims: itiscoveredbyclaimsNos.: RemarkonProtestnTheadditionalsearchfeeswereaccompaniedbythea pplicant'sprotest. F nNoprotestaccompaniedthepaymentofadditionalsearchfees. u FURTHER INFORMATION CONTINUED FROM PCT/ISA/210 This International Searching Authority found multiple (groups of) inventions in this international application, as follows: 1. Claims: 1-13 Radiodense composition for use in a method of radiation treatment of a target tissue in an animate subject 2. Claims: 14-32 A linear or branched polymer comprising alternating chelant and iodinated aromatic moieties and method of preparation. INTERNATIONALSEARCHREPORT Inte.. onal Application No nformation on patenttamily members PCT/US 99/25529 PatentdocumentPublicationPatentfamilyPublication citedinsearchreportdatemember(s)date WO9847532A29-10-1998AU7068698A13-11-1998 EP0977593A09-02-2000 US5665330A09-09-1997NONE US5008907A16-04-1991WO9014861A13-12-1990 WO9427644A08-12-1994IT1270974B26-05-1997 IT1264610B04-10-1996 AU6996594A20-12-1994 EP0703790A03-04-1996 JP8510458T05-11-1996 US5660814A26-08-1997 ZA9403816A31-01-1995 WO0025819A11-05-2000WO0025829A11-05-2000 WO0043045A27-07-2000NONE



 
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