Endre søk
RefereraExporteraLink to record
Permanent link

Direct link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Evaluation of Tumor-Targeting Properties of an Antagonistic Bombesin Analogue RM26 Conjugated with a Non-Residualizing Radioiodine Label Comparison with a Radiometal-Labelled Counterpart
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk strålningsvetenskap.ORCID-id: 0000-0003-2660-9837
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Theranostics.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Preparativ läkemedelskemi.ORCID-id: 0000-0002-9153-2832
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Theranostics.ORCID-id: 0000-0001-7921-3268
Vise andre og tillknytning
2019 (engelsk)Inngår i: Pharmaceutics, ISSN 1999-4923, E-ISSN 1999-4923, Vol. 11, nr 8, artikkel-id 380Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Radiolabelled antagonistic bombesin analogues are successfully used for targeting of gastrin-releasing peptide receptors (GRPR) that are overexpressed in prostate cancer. Internalization of antagonistic bombesin analogues is slow. We hypothesized that the use of a non-residualizing radioiodine label might not affect the tumour uptake but would reduce the retention in normal organs, where radiopharmaceutical would be internalized. To test this hypothesis, tyrosine was conjugated via diethylene glycol linker to N-terminus of an antagonistic bombesin analogue RM26 to form Tyr-PEG(2)-RM26. [In-111]In-DOTA-PEG(2)-RM26 was used as a control with a residualizing label. Tyr-PEG(2)-RM26 was labelled with I-125 with 95% radiochemical purity and retained binding specificity to GRPR. The IC50 values for Tyr-PEG(2)-RM26 and DOTA-PEG(2)-RM26 were 1.7 +/- 0.3 nM and 3.3 +/- 0.5 nM, respectively. The cellular processing of [I-125]I-Tyr-PEG(2)-RM26 by PC-3 cells showed unusually fast internalization. Biodistribution showed that uptake in pancreas and tumour was GRPR-specific for both radioconjugates. Blood clearance of [I-125]I-Tyr-PEG(2)-RM26 was appreciably slower and activity accumulation in all organs was significantly higher than for [In-111]In-DOTA-PEG(2)-RM26. Tumor uptake of [In-111]In-DOTA-PEG(2)-RM26 was significantly higher than for [I-125]I-Tyr-PEG(2)-RM26, resulting in higher tumour-to-organ ratio for [In-111]In-DOTA-PEG(2)-RM26 at studied time points. Incorporation of amino acids with hydrophilic side-chains next to tyrosine might overcome the problems associated with the use of tyrosine as a prosthetic group for radioiodination.

sted, utgiver, år, opplag, sider
MDPI, 2019. Vol. 11, nr 8, artikkel-id 380
Emneord [en]
prostate cancer, bombesin antagonistic analogue, GRPR, RM26, tyrosine, PC-3 xenografts
HSV kategori
Identifikatorer
URN: urn:nbn:se:uu:diva-394645DOI: 10.3390/pharmaceutics11080380ISI: 000484515100013PubMedID: 31382362OAI: oai:DiVA.org:uu-394645DiVA, id: diva2:1362019
Forskningsfinansiär
Swedish Research Council, 2015-02509Swedish Research Council, 2015-02353Swedish Cancer Society, CAN 2017/425Swedish Cancer Society, CAN 2018/436Tilgjengelig fra: 2019-10-17 Laget: 2019-10-17 Sist oppdatert: 2019-10-17bibliografisk kontrollert

Open Access i DiVA

fulltekst(4390 kB)59 nedlastinger
Filinformasjon
Fil FULLTEXT01.pdfFilstørrelse 4390 kBChecksum SHA-512
ff0a06e29b24a333860235e29885fcc5ddb0843662fad68e6b06bd6406fc25dec058d2a84ecd37772d37ff9b4eb82ad231ef692dd329721565abd8ad0314b108
Type fulltextMimetype application/pdf

Andre lenker

Forlagets fulltekstPubMed

Søk i DiVA

Av forfatter/redaktør
Oroujeni, MaryamAbouzayed, AymanLundmark, FannyMitran, BogdanOrlova, AnnaTolmachev, VladimirRosenström, Ulrika
Av organisasjonen
I samme tidsskrift
Pharmaceutics

Søk utenfor DiVA

GoogleGoogle Scholar
Totalt: 59 nedlastinger
Antall nedlastinger er summen av alle nedlastinger av alle fulltekster. Det kan for eksempel være tidligere versjoner som er ikke lenger tilgjengelige

doi
pubmed
urn-nbn

Altmetric

doi
pubmed
urn-nbn
Totalt: 117 treff
RefereraExporteraLink to record
Permanent link

Direct link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf