PMID- 16720236
OWN - NLM
STAT- MEDLINE
DCOM- 20060831
LR  - 20201222
IS  - 0969-8051 (Print)
IS  - 0969-8051 (Linking)
VI  - 33
IP  - 4
DP  - 2006 May
TI  - Development of 111In-labeled tumor-associated antigen peptides for monitoring 
      dendritic-cell-based vaccination.
PG  - 453-8
AB  - Dendritic cells (DC) are professional antigen-presenting cells capable of 
      inducing potent immune responses. In our ongoing clinical trials, human leukocyte 
      antigen (HLA)-A2.1+ melanoma patients are vaccinated with mature DC, presenting 
      tumor-derived peptides in major histocompatibility complexes (MHC) to naive T 
      cells. Previously, we have shown that both intradermally and intranodally 
      injected (111)In-labeled mature DC migrate to draining lymph nodes. However, 
      little is known about the fate of the MHC-peptide complex after injection of 
      these peptide-loaded DC. The aim of the present study was to develop 
      radiolabeled, tumor-derived peptides to monitor their binding to MHC Class I. 
      METHODS: The HLA-A2.1 binding peptide gp100:154-162mod (gp100:154m) was 
      conjugated with diethylenetriamine pentaacetic acid (DTPA) either at the 
      N-terminus (alpha-DTPA-gp100:154m) or at the epsilon amino group of the Lys(154) 
      residue (epsilon-DTPA-gp100:154m) and labeled with (111)In. RESULTS: The maximum 
      specific activity for both peptides was 13 GBq/micromol. The IC50 of the 
      alpha-[(111)In]DTPA-gp100:154m peptide was >75 microM. The IC50 of the 
      (111)In-labeled epsilon-DTPA-gp100:154m was 3 microM, similar to the unconjugated 
      peptide. MHC binding studies showed specific binding of the 
      epsilon-[(111)In]DTPA-gp100:154m peptide to the JY cells at 4 degrees C. 
      Interestingly, no specific binding was observed for the 
      alpha-[(111)In]DTPA-gp100:154m peptide. In contrast to the 
      alpha-[(111)In]DTPA-gp100:154m peptide, the epsilon-[(111)In]DTPA-gp100:154m 
      peptide was recognized by cytotoxic T cells. CONCLUSION: When DTPA was conjugated 
      to the epsilon NH2 group of the Lys(154) residue, MHC binding of the peptide was 
      preserved and could still be recognized by cytotoxic T cells. These studies allow 
      the noninvasive determination of the behavior of MHC-peptide complexes on DC in 
      vivo.
FAU - Laverman, Peter
AU  - Laverman P
AD  - Department of Nuclear Medicine, Radboud University Nijmegen Medical Centre, PO 
      Box 9101, 6500 HB Nijmegen, The Netherlands. p.laverman@nucmed.umcn.nl
FAU - de Vries, I Jolanda M
AU  - de Vries IJ
FAU - Scharenborg, Nicole M
AU  - Scharenborg NM
FAU - de Boer, Annemiek
AU  - de Boer A
FAU - Broekema, Matthias
AU  - Broekema M
FAU - Oyen, Wim J G
AU  - Oyen WJ
FAU - Figdor, Carl G
AU  - Figdor CG
FAU - Adema, Gosse J
AU  - Adema GJ
FAU - Boerman, Otto C
AU  - Boerman OC
LA  - eng
PT  - Journal Article
DEP - 20060502
PL  - United States
TA  - Nucl Med Biol
JT  - Nuclear medicine and biology
JID - 9304420
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Cancer Vaccines)
RN  - 0 (HLA-A2 Antigen)
RN  - 0 (Indium Radioisotopes)
RN  - 0 (Peptides)
RN  - 0 (Radiopharmaceuticals)
SB  - IM
MH  - Antineoplastic Agents/immunology/therapeutic use
MH  - Binding Sites
MH  - Cancer Vaccines/*immunology/therapeutic use
MH  - Cell Line, Tumor
MH  - Dendritic Cells/diagnostic imaging/immunology/*transplantation
MH  - HLA-A2 Antigen/*immunology
MH  - Humans
MH  - *Indium Radioisotopes/immunology
MH  - Peptides/*immunology
MH  - Protein Binding
MH  - Radionuclide Imaging
MH  - Radiopharmaceuticals/immunology
EDAT- 2006/05/25 09:00
MHDA- 2006/09/01 09:00
CRDT- 2006/05/25 09:00
PHST- 2005/12/22 00:00 [received]
PHST- 2006/01/18 00:00 [revised]
PHST- 2006/02/26 00:00 [accepted]
PHST- 2006/05/25 09:00 [pubmed]
PHST- 2006/09/01 09:00 [medline]
PHST- 2006/05/25 09:00 [entrez]
AID - S0969-8051(06)00035-7 [pii]
AID - 10.1016/j.nucmedbio.2006.02.005 [doi]
PST - ppublish
SO  - Nucl Med Biol. 2006 May;33(4):453-8. doi: 10.1016/j.nucmedbio.2006.02.005. Epub 
      2006 May 2.