Optimization of dendrimer structure for sentinel lymph node imaging: Effects of generation and terminal group.
The detection of the sentinel lymph node (SLN), the first lymph node draining tumor cells, is important in cancer diagnosis and therapy. Dendrimers are synthetic macromolecules with highly controllable structures, and are potent multifunctional imaging agents. In this study, 12 types of dendrimer of different generations (G2, G4, G6, and G8) and different terminal groups (amino, carboxyl, and acetyl) were prepared to determine the optimal dendrimer structure for SLN imaging. Radiolabeled dendrimers were intradermally administrated to the right footpads of rats. All G2 dendrimers were predominantly accumulated in the kidney. Amino-terminal, acetyl-terminal, and carboxyl-terminal dendrimers of greater than G4 were mostly located at the injection site, in the blood, and in the SLN, respectively. The carboxyl-terminal dendrimers were largely unrecognized by macrophages and T-cells in the SLN. Finally, SLN detection was successfully performed by single photon emission computed tomography imaging using carboxyl-terminal dendrimers of greater than G4.


BACKGROUND
The early detection of tumor cells in the sentinel draining lymph nodes (SLN) is of utmost importance in terms of determining cancer prognosis and devising treatment. In this article, the authors investigated various formulations of dendrimers to determine the optimal one for tumor detection. The data generated from this study would help clinicians to fight the cancer battle in the near future.
Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, Sakai, Osaka, Japan.
Yuichiro
Y
Niki
Medical Photonics Research Center, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
Mikako
M
Ogawa
Department of Materials Science, Graduate School of Engineering, Osaka Prefecture University, Sakai, Osaka, Japan.
Rie
R
Makiura
Medical Photonics Research Center, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
Yasuhiro
Y
Magata
Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, Sakai, Osaka, Japan. Electronic address: kojima@chem.osakafu-u.ac.jp.
Chie
C
Kojima
D000818:Animals; D050091:Dendrimers / Q000737:chemistry* / Q000493:pharmacokinetics*; D008198:Lymph Nodes / Q000473:pathology*; D008297:Male; D009369:Neoplasms / Q000175:diagnosis / Q000473:pathology*; D011379:Prognosis; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
D050091:Dendrimers; C104700:PAMAM Starburst; D019275:Radiopharmaceuticals
Biodistribution; Dendrimer; Imaging; Sentinel lymph node; Single photon emission computed tomography