PMID- 28159813
OWN - NLM
STAT- MEDLINE
DCOM- 20180601
LR  - 20181202
IS  - 1557-3265 (Electronic)
IS  - 1078-0432 (Linking)
VI  - 23
IP  - 14
DP  - 2017 Jul 15
TI  - Correlation between Ferumoxytol Uptake in Tumor Lesions by MRI and Response to 
      Nanoliposomal Irinotecan in Patients with Advanced Solid Tumors: A Pilot Study.
PG  - 3638-3648
LID - 10.1158/1078-0432.CCR-16-1990 [doi]
AB  - Purpose: To determine whether deposition characteristics of ferumoxytol (FMX) 
      iron nanoparticles in tumors, identified by quantitative MRI, may predict tumor 
      lesion response to nanoliposomal irinotecan (nal-IRI).Experimental Design: 
      Eligible patients with previously treated solid tumors had FMX-MRI scans before 
      and following (1, 24, and 72 hours) FMX injection. After MRI acquisition, R2* 
      signal was used to calculate FMX levels in plasma, reference tissue, and tumor 
      lesions by comparison with a phantom-based standard curve. Patients then received 
      nal-IRI (70 mg/m(2) free base strength) biweekly until progression. Two 
      percutaneous core biopsies were collected from selected tumor lesions 72 hours 
      after FMX or nal-IRI.Results: Iron particle levels were quantified by FMX-MRI in 
      plasma, reference tissues, and tumor lesions in 13 of 15 eligible patients. On 
      the basis of a mechanistic pharmacokinetic model, tissue permeability to FMX 
      correlated with early FMX-MRI signals at 1 and 24 hours, while FMX tissue binding 
      contributed at 72 hours. Higher FMX levels (ranked relative to median value of 
      multiple evaluable lesions from 9 patients) were significantly associated with 
      reduction in lesion size by RECIST v1.1 at early time points (P < 0.001 at 1 hour 
      and P < 0.003 at 24 hours FMX-MRI, one-way ANOVA). No association was observed 
      with post-FMX levels at 72 hours. Irinotecan drug levels in lesions correlated 
      with patient's time on treatment (Spearman rho = 0.7824; P = 0.0016).Conclusions: 
      Correlation between FMX levels in tumor lesions and nal-IRI activity suggests 
      that lesion permeability to FMX and subsequent tumor uptake may be a useful 
      noninvasive and predictive biomarker for nal-IRI response in patients with solid 
      tumors. Clin Cancer Res; 23(14); 3638-48. (c)2017 AACR.
CI  - (c)2017 American Association for Cancer Research.
FAU - Ramanathan, Ramesh K
AU  - Ramanathan RK
AD  - Virginia G Piper Cancer Center, Honor Healthcare, Scottsdale, Arizona. 
      Ramanathan.ramesh@mayo.edu Sklinz@merrimack.com.
AD  - Translational Genomics Research Institute, Phoenix, Arizona.
FAU - Korn, Ronald L
AU  - Korn RL
AD  - Virginia G Piper Cancer Center, Honor Healthcare, Scottsdale, Arizona.
AD  - Imaging Endpoints, Scottsdale, Arizona.
FAU - Raghunand, Natarajan
AU  - Raghunand N
AD  - Moffitt Cancer Center, Tampa, Florida.
FAU - Sachdev, Jasgit C
AU  - Sachdev JC
AD  - Virginia G Piper Cancer Center, Honor Healthcare, Scottsdale, Arizona.
FAU - Newbold, Ronald G
AU  - Newbold RG
AD  - Virginia G Piper Cancer Center, Honor Healthcare, Scottsdale, Arizona.
AD  - Imaging Endpoints, Scottsdale, Arizona.
FAU - Jameson, Gayle
AU  - Jameson G
AD  - Virginia G Piper Cancer Center, Honor Healthcare, Scottsdale, Arizona.
FAU - Fetterly, Gerald J
AU  - Fetterly GJ
AD  - Roswell Park Cancer Institute, Buffalo, New York.
FAU - Prey, Joshua
AU  - Prey J
AD  - Roswell Park Cancer Institute, Buffalo, New York.
FAU - Klinz, Stephan G
AU  - Klinz SG
AD  - Merrimack Pharmaceuticals, Inc., Cambridge, Massachusetts. 
      Ramanathan.ramesh@mayo.edu Sklinz@merrimack.com.
FAU - Kim, Jaeyeon
AU  - Kim J
AD  - Merrimack Pharmaceuticals, Inc., Cambridge, Massachusetts.
FAU - Cain, Jason
AU  - Cain J
AD  - Merrimack Pharmaceuticals, Inc., Cambridge, Massachusetts.
FAU - Hendriks, Bart S
AU  - Hendriks BS
AD  - Merrimack Pharmaceuticals, Inc., Cambridge, Massachusetts.
FAU - Drummond, Daryl C
AU  - Drummond DC
AD  - Merrimack Pharmaceuticals, Inc., Cambridge, Massachusetts.
FAU - Bayever, Eliel
AU  - Bayever E
AD  - Merrimack Pharmaceuticals, Inc., Cambridge, Massachusetts.
FAU - Fitzgerald, Jonathan B
AU  - Fitzgerald JB
AD  - Merrimack Pharmaceuticals, Inc., Cambridge, Massachusetts.
LA  - eng
PT  - Journal Article
DEP - 20170203
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Liposomes)
RN  - 7673326042 (Irinotecan)
RN  - XM0M87F357 (Ferrosoferric Oxide)
RN  - XT3Z54Z28A (Camptothecin)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Camptothecin/administration & dosage/*analogs & derivatives/blood/chemistry
MH  - Disease-Free Survival
MH  - Female
MH  - Ferrosoferric Oxide/*administration & dosage/blood/chemistry
MH  - Humans
MH  - Irinotecan
MH  - Liposomes/administration & dosage/chemistry
MH  - Magnetic Resonance Imaging
MH  - Male
MH  - Middle Aged
MH  - Nanoparticles/administration & dosage/chemistry
MH  - Neoplasms/diagnostic imaging/*drug therapy/pathology
MH  - Pilot Projects
EDAT- 2017/02/06 06:00
MHDA- 2018/06/02 06:00
CRDT- 2017/02/05 06:00
PHST- 2016/08/11 00:00 [received]
PHST- 2017/01/19 00:00 [revised]
PHST- 2017/01/20 00:00 [accepted]
PHST- 2017/02/06 06:00 [pubmed]
PHST- 2018/06/02 06:00 [medline]
PHST- 2017/02/05 06:00 [entrez]
AID - 1078-0432.CCR-16-1990 [pii]
AID - 10.1158/1078-0432.CCR-16-1990 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2017 Jul 15;23(14):3638-3648. doi: 
      10.1158/1078-0432.CCR-16-1990. Epub 2017 Feb 3.