PMID- 32335736
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231113
IS  - 2191-219X (Print)
IS  - 2191-219X (Electronic)
IS  - 2191-219X (Linking)
VI  - 10
IP  - 1
DP  - 2020 Apr 25
TI  - Toxicity of a combined therapy using the mTOR-inhibitor everolimus and PRRT with 
      [(177)Lu]Lu-DOTA-TATE in Lewis rats.
PG  - 41
LID - 10.1186/s13550-020-00628-y [doi]
LID - 41
AB  - PURPOSE: Peptide receptor radionuclide therapy (PRRT) with 
      [(177)Lu]Lu-DOTA(0),TYR(3)-octreotate ([(177)Lu]Lu-DOTA-TATE) and the mechanistic 
      target of rapamycin (mTOR) inhibitor everolimus are both approved for the 
      treatment of neuroendocrine tumours (NET). However, tumour progression is still 
      frequent, and treatment strategies need further improvement. One possible 
      approach could be to combine different therapy options. In this study, we 
      investigated the toxicity of a combined treatment with everolimus and 
      [(177)Lu]Lu-DOTA-TATE in female Lewis rats. METHODS: Animals received 200 MBq of 
      [(177)Lu]Lu-DOTA-TATE once and/or 5 mg/kg body weight everolimus or placebo 
      weekly for 16 weeks and were divided into four groups (group 1, placebo; group 2, 
      everolimus; group 3, placebo + [(177)Lu]Lu-DOTA-TATE; group 4, everolimus + 
      [(177)Lu]Lu-DOTA-TATE). Blood levels of creatinine and blood urea nitrogen (BUN) 
      were assessed weekly to monitor nephrotoxicity, and a full blood count was 
      performed at the time of euthanasia to monitor myelotoxicity. Additionally, renal 
      function was analysed by sequential [(99m)Tc]Tc-mercaptoacetyltriglycine 
      ([(99m)Tc]Tc-MAG3) scintigraphies. Histopathological examination was performed in 
      all the kidneys using a standardized renal damage score (RDS). RESULTS: Rats 
      receiving everolimus showed a significantly lower increase in creatinine levels 
      than those receiving placebo. Everolimus therapy reduced white blood count 
      significantly, which was not observed for [(177)Lu]Lu-DOTA-TATE. Functional renal 
      scintigraphies using [(99m)Tc]Tc-MAG3 showed a compromised initial tracer uptake 
      after PRRT and slower but still preserved excretion after everolimus. Histology 
      showed no significant RDS differences between groups. CONCLUSION: Renal 
      scintigraphy is a highly sensitive tool for the detection of renal function 
      impairment after a combination of everolimus and PRRT. Additional treatment with 
      everolimus does not increase renal and haematological toxicity of PRRT with 
      [(177)Lu]Lu-DOTA-TATE.
FAU - Zellmer, Johannes
AU  - Zellmer J
AD  - Department of Nuclear Medicine, University Hospital, 
      Ludwig-Maxilimians-University Munich, Munich, Germany.
FAU - Yen, Hsi-Yu
AU  - Yen HY
AD  - Department of Pathology, Technical University of Munich, Munich, Germany.
AD  - German Cancer Consortium (DKTK), German Cancer Research Centre (DKFZ), 
      Heidelberg, Germany.
AD  - Comparative Experimental Pathology, Technical University of Munich, Munich, 
      Germany.
FAU - Kaiser, Lena
AU  - Kaiser L
AD  - Department of Nuclear Medicine, University Hospital, 
      Ludwig-Maxilimians-University Munich, Munich, Germany.
FAU - Mille, Erik
AU  - Mille E
AD  - Department of Nuclear Medicine, University Hospital, 
      Ludwig-Maxilimians-University Munich, Munich, Germany.
FAU - Gildehaus, Franz Josef
AU  - Gildehaus FJ
AD  - Department of Nuclear Medicine, University Hospital, 
      Ludwig-Maxilimians-University Munich, Munich, Germany.
FAU - Boning, Guido
AU  - Boning G
AD  - Department of Nuclear Medicine, University Hospital, 
      Ludwig-Maxilimians-University Munich, Munich, Germany.
FAU - Steiger, Katja
AU  - Steiger K
AD  - Department of Pathology, Technical University of Munich, Munich, Germany.
AD  - Comparative Experimental Pathology, Technical University of Munich, Munich, 
      Germany.
FAU - Hacker, Marcus
AU  - Hacker M
AD  - Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear 
      Medicine, Medical University of Vienna, Vienna, Austria.
FAU - Bartenstein, Peter
AU  - Bartenstein P
AD  - Department of Nuclear Medicine, University Hospital, 
      Ludwig-Maxilimians-University Munich, Munich, Germany.
FAU - Todica, Andrei
AU  - Todica A
AD  - Department of Nuclear Medicine, University Hospital, 
      Ludwig-Maxilimians-University Munich, Munich, Germany.
FAU - Haug, Alexander R
AU  - Haug AR
AD  - Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear 
      Medicine, Medical University of Vienna, Vienna, Austria.
FAU - Ilhan, Harun
AU  - Ilhan H
AD  - Department of Nuclear Medicine, University Hospital, 
      Ludwig-Maxilimians-University Munich, Munich, Germany. 
      harun.ilhan@med.uni-muenchen.de.
LA  - eng
PT  - Journal Article
DEP - 20200425
PL  - Germany
TA  - EJNMMI Res
JT  - EJNMMI research
JID - 101560946
PMC - PMC7183514
OTO - NOTNLM
OT  - Everolimus
OT  - PRRT
OT  - Renal clearance
OT  - Scintigraphy
OT  - [177Lu]Lu-DOTA-TATE
COIS- The authors declare that they have no competing interests.
EDAT- 2020/04/27 06:00
MHDA- 2020/04/27 06:01
PMCR- 2020/04/25
CRDT- 2020/04/27 06:00
PHST- 2019/11/14 00:00 [received]
PHST- 2020/04/07 00:00 [accepted]
PHST- 2020/04/27 06:00 [entrez]
PHST- 2020/04/27 06:00 [pubmed]
PHST- 2020/04/27 06:01 [medline]
PHST- 2020/04/25 00:00 [pmc-release]
AID - 10.1186/s13550-020-00628-y [pii]
AID - 628 [pii]
AID - 10.1186/s13550-020-00628-y [doi]
PST - epublish
SO  - EJNMMI Res. 2020 Apr 25;10(1):41. doi: 10.1186/s13550-020-00628-y.