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  • Kristiansson, AmandaLund University,Lunds universitet,Infektionsmedicin,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Antioxidationsmedicin,Forskargrupper vid Lunds universitet,Infection Medicine (BMC),Section III,Department of Clinical Sciences, Lund,Faculty of Medicine,Antioxidation medicine,Lund University Research Groups (författare)

177Lu-PSMA-617 Therapy in Mice, with or without the Antioxidant α1-Microglobulin (A1M), Including Kidney Damage Assessment Using 99mTc-MAG3 Imaging

  • Artikel/kapitelEngelska2021

Förlag, utgivningsår, omfång ...

  • 2021-02-10
  • MDPI AG,2021

Nummerbeteckningar

  • LIBRIS-ID:oai:lup.lub.lu.se:c6d481a8-5aaa-47bd-b441-abebbe2fccec
  • https://lup.lub.lu.se/record/c6d481a8-5aaa-47bd-b441-abebbe2fccecURI
  • https://doi.org/10.3390/biom11020263DOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:art swepub-publicationtype
  • Ämneskategori:ref swepub-contenttype

Anmärkningar

  • Anti-prostate specific membrane antigen (PSMA) radioligand therapy is promising but not curative in castration resistant prostate cancer. One way to broaden the therapeutic index could be to administer higher doses in combination with radioprotectors, since administered radioactivity is kept low today in order to avoid side-effects from a high absorbed dose to healthy tissue. Here, we investigated the human radical scavenger α1-microglobulin (A1M) together with 177-Lutetium (177Lu) labeled PSMA-617 in preclinical models with respect to therapeutic efficacy and kidney toxicity. Nude mice with subcutaneous LNCaP xenografts were injected with 50 or 100 MBq of [177Lu]Lu-PSMA-617, with or without injections of recombinant A1M (rA1M) (at T = 0 and T = 24 h). Kidney absorbed dose was calculated to 7.36 Gy at 4 days post a 100 MBq injection. Activity distribution was imaged with Single-Photon Emission Computed Tomography (SPECT) at 24 h. Tumor volumes were measured continuously, and kidneys and blood were collected at termination (3-4 days and 3-4 weeks after injections). In a parallel set of experiments, mice were given [177Lu]Lu-PSMA-617 and rA1M as above and dynamic technetium-99m mercaptoacetyltriglycine ([99mTc]Tc-MAG3) SPECT imaging was performed prior to injection, and 3- and 6-months post injection. Blood and urine were continuously sampled. At termination (6 months) the kidneys were resected. Biomarkers of kidney function, expression of stress genes and kidney histopathology were analyzed. [177Lu]Lu-PSMA-617 uptake, in tumors and kidneys, as well as treatment efficacy did not differ between rA1M and vehicle groups. In mice given rA1M, [99mTc]Tc-MAG3 imaging revealed a significantly higher slope of initial uptake at three months compared to mice co-injected with [177Lu]Lu-PSMA-617 and vehicle. Little or no change compared to control was seen in urine albumin, serum/plasma urea levels, RT-qPCR analysis of stress response genes and in the kidney histopathological evaluation. In conclusion, [99mTc]Tc-MAG3 imaging presented itself as a sensitive tool to detect changes in kidney function revealing that administration of rA1M has a potentially positive effect on kidney perfusion and tubular function when combined with [177Lu]Lu-PSMA-617 therapy. Furthermore, we could show that rA1M did not affect anti-PSMA radioligand therapy efficacy.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Örbom, AndersLund University,Lunds universitet,Forskningsgruppen för Systemisk strålterapi,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Strålterapi,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Systemic Radiation Therapy Group,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Radiation therapy,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)med-aom (författare)
  • Ahlstedt, JonasLund University,Lunds universitet,Ergonomi och aerosolteknologi,Institutionen för designvetenskaper,Institutioner vid LTH,Lunds Tekniska Högskola,Lund University Bioimaging Center,Medicinska fakulteten,Ergonomics and Aerosol Technology,Department of Design Sciences,Departments at LTH,Faculty of Engineering, LTH,Faculty of Medicine(Swepub:lu)med-jat (författare)
  • Karlsson, HelenaLund University,Lunds universitet,Neonatologi,Forskargrupper vid Lunds universitet,Neonatology,Lund University Research Groups(Swepub:lu)he4542ka (författare)
  • Zedan, WahedLund University,Lunds universitet,Forskningsgruppen för Systemisk strålterapi,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Strålterapi,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Systemic Radiation Therapy Group,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Radiation therapy,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)med-wez (författare)
  • Gram, MagnusLund University,Lunds universitet,Neonatologi,Forskargrupper vid Lunds universitet,Sjukdomsorsakande oxidation,Neonatology,Lund University Research Groups,Redox Medicine(Swepub:lu)medk-mo0 (författare)
  • Åkerström, BoLund University,Lunds universitet,Infektionsmedicin,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Antioxidationsmedicin,Forskargrupper vid Lunds universitet,Infection Medicine (BMC),Section III,Department of Clinical Sciences, Lund,Faculty of Medicine,Antioxidation medicine,Lund University Research Groups(Swepub:lu)medk-bak (författare)
  • Strand, Sven-ErikLund University,Lunds universitet,Medicinsk strålningsfysik, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Forskningsgruppen för Systemisk strålterapi,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Strålterapi,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medical Radiation Physics, Lund,Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,Systemic Radiation Therapy Group,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Radiation therapy,Section I,Department of Clinical Sciences, Lund(Swepub:lu)rafy-ses (författare)
  • Altai, MohamedLund University,Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Strålterapi,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Radiation therapy,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)mo8753al (författare)
  • Strand, JoannaLund University,Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Strålterapi,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Radiation therapy,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)jo5371st (författare)
  • Vilhelmsson Timmermand, OskarLund University,Lunds universitet,Forskningsgruppen för Systemisk strålterapi,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Strålterapi,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Systemic Radiation Therapy Group,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Radiation therapy,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)immu-orv (författare)
  • InfektionsmedicinSektion III (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Biomolecules: MDPI AG11:22218-273X

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