PMID- 29627705
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240328
IS  - 1936-5233 (Print)
IS  - 1936-5233 (Electronic)
IS  - 1936-5233 (Linking)
VI  - 11
IP  - 3
DP  - 2018 Jun
TI  - 3D Imaging Detection of HER2 Based in the Use of Novel Affibody-Quantum Dots 
      Probes and Ratiometric Analysis.
PG  - 672-685
LID - S1936-5233(18)30006-8 [pii]
LID - 10.1016/j.tranon.2018.03.004 [doi]
AB  - Patients with breast cancer (BC) overexpressing HER2 (HER2+) are selected for 
      Trastuzumab treatment, which blocks HER2 and improves cancer prognosis. However, 
      HER2+ diagnosis, by the gold standard, immunohistochemistry, could lead to 
      errors, associated to: a) variability in sample manipulation (thin 2D sections), 
      b) use of subjective algorithms, and c) heterogeneity of HER2 expression within 
      the tissue. Therefore, we explored HER2 3D detection by multiplexed imaging of 
      Affibody-Quantum Dots conjugates (Aff-QD), ratiometric analysis (RMA(FI)) and 
      thresholding, using BC multicellular tumor spheroids (BC-MTS) (~120 mum of 
      diameter) as 3D model of BC. HER2+, HER2- and hybrid HER2+/- BC-MTS (mimicking 
      heterogeneous tissue) were incubated simultaneously with two Aff-QD probes 
      (anti-HER2 and negative control (NC), respectively, (1:1)). Confocal XY sections 
      were recorded along the Z distance, and processed by automatized RMA(FI) 
      (anti-HER2 Aff-QD/ NC). Quantifying the NC fluorescence allowed to predict the 
      fraction of non-specific accumulation of the anti-HER2 probe within the thick 
      sample, and resolve the specific HER2 level. HER2 was detected up to 30mum within 
      intact BC-MTS, however, permeabilization improved detection up to 70mum. Specific 
      HER2 signal was objectively quantified, and HER2 3D-density of 9.2, 48.3 and 
      30.8% were obtained in HER2-, HER2+ and hybrid HER2+/- permeabilized BC-MTS, 
      respectively. Therefore, by combining the multiplexing capacity of Aff-QD probes 
      and RMA(FI), we overcame the challenge of non-specific probe accumulation in 3D 
      samples with minimal processing, yielding a fast, specific spatial HER2 detection 
      and objective quantification.
CI  - Copyright (c) 2018 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Perez-Trevino, Perla
AU  - Perez-Trevino P
AD  - Tecnologico de Monterrey, Escuela de Medicina, Av. Morones Prieto No. 3000 Pte., 
      Monterrey, NL, Mexico, 64710.
FAU - la Cerda, Hector Hernandez-De
AU  - la Cerda HH
AD  - Tecnologico de Monterrey, Escuela de Medicina, Av. Morones Prieto No. 3000 Pte., 
      Monterrey, NL, Mexico, 64710.
FAU - Perez-Trevino, Jorge
AU  - Perez-Trevino J
AD  - Tecnologico de Monterrey, Escuela de Medicina, Av. Morones Prieto No. 3000 Pte., 
      Monterrey, NL, Mexico, 64710.
FAU - Fajardo-Ramirez, Oscar Raul
AU  - Fajardo-Ramirez OR
AD  - Tecnologico de Monterrey, Escuela de Medicina, Av. Morones Prieto No. 3000 Pte., 
      Monterrey, NL, Mexico, 64710.
FAU - Garcia, Noemi
AU  - Garcia N
AD  - Tecnologico de Monterrey, Escuela de Medicina, Av. Morones Prieto No. 3000 Pte., 
      Monterrey, NL, Mexico, 64710.
FAU - Altamirano, Julio
AU  - Altamirano J
AD  - Tecnologico de Monterrey, Escuela de Medicina, Av. Morones Prieto No. 3000 Pte., 
      Monterrey, NL, Mexico, 64710. Electronic address: altamirano@itesm.mx.
LA  - eng
PT  - Journal Article
DEP - 20180405
PL  - United States
TA  - Transl Oncol
JT  - Translational oncology
JID - 101472619
PMC - PMC6053773
EDAT- 2018/04/09 06:00
MHDA- 2018/04/09 06:01
PMCR- 2018/04/05
CRDT- 2018/04/09 06:00
PHST- 2017/12/21 00:00 [received]
PHST- 2018/03/08 00:00 [revised]
PHST- 2018/03/12 00:00 [accepted]
PHST- 2018/04/09 06:00 [pubmed]
PHST- 2018/04/09 06:01 [medline]
PHST- 2018/04/09 06:00 [entrez]
PHST- 2018/04/05 00:00 [pmc-release]
AID - S1936-5233(18)30006-8 [pii]
AID - 10.1016/j.tranon.2018.03.004 [doi]
PST - ppublish
SO  - Transl Oncol. 2018 Jun;11(3):672-685. doi: 10.1016/j.tranon.2018.03.004. Epub 
      2018 Apr 5.