PMID- 7671250
OWN - NLM
STAT- MEDLINE
DCOM- 19951019
LR  - 20181130
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 55
IP  - 19
DP  - 1995 Oct 1
TI  - Tumor-specific anti-epidermal growth factor receptor variant III monoclonal 
      antibodies: use of the tyramine-cellobiose radioiodination method enhances 
      cellular retention and uptake in tumor xenografts.
PG  - 4375-82
AB  - Amplification and rearrangement of the epidermal growth factor receptor (EGFR) 
      gene are characteristics of many types of tumors. One class of EGFR mutations, 
      EGFRvIII, is characterized by an in-frame deletion resulting in a truncated 
      external domain of the receptor. EGFRvIII was first identified in a subset of 
      gliomas and has since been found in some non-small cell lung carcinomas and 
      breast carcinomas. mAbs specific for this variant form of EGFR but unreactive 
      with the wild-type EGFR have been reported from our laboratory. This study 
      further characterizes three of these antibodies. We determined, via radiolabeling 
      techniques and immunofluorescence microscopy, that, after cell binding in vitro, 
      the anti-EGFRvIII-specific mAbs internalize at 37 degrees C. Furthermore, 
      subsequent to internalization, the antibodies were processed intracellularly, 
      presumably by lysosomal degradation. We also examined the use of an alternative 
      radiolabeling procedure that uses nonmetabolizable radio-iodinated tyramine 
      cellobiose. Our results show that the tyramine cellobiose labeling method allows 
      for greater tumor cell retention of radiolabel in vitro (76% for tyramine 
      cellobiose and 27% for Iodo-Gen after 24 h). Paired-label biodistribution studies 
      in athymic mice indicate that anti-EGFRvIII mAb L8A4 localizes specifically to 
      EGFRvIII-expressing tumor xenografts with a maximum of 34.3 +/- 7.6% injected 
      dose/g when labeled using tyramine cellobiose compared with a maximum of 14.9 +/- 
      4.3% injected dose/g using Iodo-Gen; similar results were obtained with mAb H10. 
      These results suggest that the anti-EGFRvIII mAbs may serve as potential carriers 
      for radioconjugate- and immunotoxin-based therapies for tumors expressing 
      EGFRvIII.
FAU - Reist, C J
AU  - Reist CJ
AD  - Department of Pathology, Duke University Medical Center, Durham, North Carolina 
      27710, USA.
FAU - Archer, G E
AU  - Archer GE
FAU - Kurpad, S N
AU  - Kurpad SN
FAU - Wikstrand, C J
AU  - Wikstrand CJ
FAU - Vaidyanathan, G
AU  - Vaidyanathan G
FAU - Willingham, M C
AU  - Willingham MC
FAU - Moscatello, D K
AU  - Moscatello DK
FAU - Wong, A J
AU  - Wong AJ
FAU - Bigner, D D
AU  - Bigner DD
FAU - Zalutsky, M R
AU  - Zalutsky MR
LA  - eng
GR  - CA 11898/CA/NCI NIH HHS/United States
GR  - CA 56115/CA/NCI NIH HHS/United States
GR  - NS 20023/NS/NINDS NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Drug Carriers)
RN  - 0 (Iodine Radioisotopes)
RN  - 16462-44-5 (Cellobiose)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - X8ZC7V0OX3 (Tyramine)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal/*pharmacokinetics/therapeutic use
MH  - Cellobiose
MH  - Drug Carriers
MH  - ErbB Receptors/analysis/*immunology
MH  - Iodine Radioisotopes/*pharmacokinetics
MH  - Isotope Labeling/*methods
MH  - Mice
MH  - Microscopy, Fluorescence
MH  - Neoplasm Transplantation
MH  - Neoplasms, Experimental/*metabolism/therapy
MH  - Radiation Dosage
MH  - Tissue Distribution
MH  - Transplantation, Heterologous
MH  - Tyramine
EDAT- 1995/10/01 00:00
MHDA- 1995/10/01 00:01
CRDT- 1995/10/01 00:00
PHST- 1995/10/01 00:00 [pubmed]
PHST- 1995/10/01 00:01 [medline]
PHST- 1995/10/01 00:00 [entrez]
PST - ppublish
SO  - Cancer Res. 1995 Oct 1;55(19):4375-82.