PMID- 30809314
OWN - NLM
STAT- MEDLINE
DCOM- 20191212
LR  - 20200309
IS  - 1838-7640 (Electronic)
IS  - 1838-7640 (Linking)
VI  - 9
IP  - 3
DP  - 2019
TI  - Radioembolization of Hepatocellular Carcinoma with Built-In Dosimetry: First in 
      vivo Results with Uniformly-Sized, Biodegradable Microspheres Labeled with 
      (188)Re.
PG  - 868-883
LID - 10.7150/thno.29381 [doi]
AB  - A common form of treatment for patients with hepatocellular carcinoma (HCC) is 
      transarterial radioembolization (TARE) with non-degradable glass or resin 
      microspheres (MS) labeled with (90)Y ((90)Y-MS). To further simplify the 
      dosimetry calculations in the clinical setting, to have more control over the 
      particle size and to change the permanent embolization to a temporary one, we 
      developed uniformly-sized, biodegradable (188)Re-labeled MS ((188)Re-MS) as a new 
      and easily imageable TARE agent. Methods: MS made of poly(L-lactic acid) were 
      produced in a flow focusing microchip. The MS were labeled with (188)Re using a 
      customized kit. An orthotopic HCC animal model was developed in male Sprague 
      Dawley rats by injecting N1-S1 cells directly into the liver using ultrasound 
      guidance. A suspension of (188)Re-MS was administered via hepatic intra-arterial 
      catheterization 2 weeks post-inoculation of the N1-S1 cells. The rats were imaged 
      by SPECT 1, 24, 48, and 72 h post-radioembolization. Results: The spherical 
      (188)Re-MS had a diameter of 41.8 +/- 6.0 microm (CV = 14.5%). The site and the depth 
      of the injection of N1-S1 cells were controlled by visualization of the liver in 
      sonograms. Single 0.5 g tumors were grown in all rats. (188)Re-MS accumulated in 
      the liver with no deposition in the lungs. (188)Re decays to stable (188)Os by 
      emission of beta( ) particles with similar energy to those emitted by (90)Y while 
      simultaneously emitting gamma photons, which were imaged directly by single photon 
      computed tomography (SPECT). Using Monte Carlo methods, the dose to the tumors 
      was calculated to be 3-6 times larger than to the healthy liver tissue. 
      Conclusions:(188)Re-MS have the potential to become the next generation of 
      beta( )-emitting MS for TARE. Future work revolves around the investigation of the 
      therapeutic potential of (188)Re-MS in a large-scale, long-term preclinical study 
      as well as the evaluation of the clinical outcomes of using (188)Re-MS with 
      different sizes, from 20 to 50 microm.
FAU - De La Vega, Jose Carlos
AU  - De La Vega JC
AD  - Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC 
      Canada.
FAU - Esquinas, Pedro Luis
AU  - Esquinas PL
AD  - Department of Radiology, University of British Columbia, Vancouver, BC Canada.
FAU - Rodriguez-Rodriguez, Cristina
AU  - Rodriguez-Rodriguez C
AD  - Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC 
      Canada.
AD  - Department of Physics and Astronomy, University of British Columbia, Vancouver, 
      BC Canada.
FAU - Bokharaei, Mehrdad
AU  - Bokharaei M
AD  - Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC 
      Canada.
FAU - Moskalev, Igor
AU  - Moskalev I
AD  - The Vancouver Prostate Cancer Centre and Department of Urologic Sciences, 
      University of British Columbia, Vancouver, BC Canada.
FAU - Liu, David
AU  - Liu D
AD  - Department of Interventional Radiology, Vancouver General Hospital, Vancouver, BC 
      Canada.
FAU - Saatchi, Katayoun
AU  - Saatchi K
AD  - Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC 
      Canada.
FAU - Hafeli, Urs O
AU  - Hafeli UO
AD  - Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC 
      Canada.
LA  - eng
GR  - CIHR/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190125
PL  - Australia
TA  - Theranostics
JT  - Theranostics
JID - 101552395
RN  - 0 (Drug Carriers)
RN  - 0 (Polyesters)
RN  - 0 (Radioisotopes)
RN  - 459TN2L5F5 (poly(lactide))
RN  - 7440-15-5 (Rhenium)
SB  - IM
MH  - Animals
MH  - Carcinoma, Hepatocellular/diagnosis/*therapy
MH  - Disease Models, Animal
MH  - *Drug Carriers
MH  - Embolization, Therapeutic/*methods
MH  - Humans
MH  - In Vivo Dosimetry/methods
MH  - Liver Neoplasms/diagnosis/therapy
MH  - *Microspheres
MH  - Polyesters
MH  - Radioisotopes/*administration & dosage
MH  - Radiotherapy/*methods
MH  - Rats, Sprague-Dawley
MH  - Rhenium/*administration & dosage
MH  - Treatment Outcome
PMC - PMC6376476
OTO - NOTNLM
OT  - 188Re
OT  - beta radiation therapy
OT  - liver cancer
OT  - microspheres
OT  - monosized
OT  - radioembolization
COIS- Competing Interests: The authors have declared that no competing interest exists.
EDAT- 2019/02/28 06:00
MHDA- 2019/12/18 06:00
PMCR- 2019/01/01
CRDT- 2019/02/28 06:00
PHST- 2018/08/21 00:00 [received]
PHST- 2019/01/02 00:00 [accepted]
PHST- 2019/02/28 06:00 [entrez]
PHST- 2019/02/28 06:00 [pubmed]
PHST- 2019/12/18 06:00 [medline]
PHST- 2019/01/01 00:00 [pmc-release]
AID - thnov09p0868 [pii]
AID - 10.7150/thno.29381 [doi]
PST - epublish
SO  - Theranostics. 2019 Jan 25;9(3):868-883. doi: 10.7150/thno.29381. eCollection 
      2019.