RT Journal Article
SR Electronic
T1 In Vivo Imaging of Natural Killer Cell Trafficking in Tumors
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1575
OP 1580
DO 10.2967/jnumed.114.152918
VO 56
IS 10
A1 Filippo Galli
A1 Anna Serafina Rapisarda
A1 Helena Stabile
A1 Gaurav Malviya
A1 Isabella Manni
A1 Elena Bonanno
A1 Giulia Piaggio
A1 Angela Gismondi
A1 Angela Santoni
A1 Alberto Signore
YR 2015
UL http://jnm.snmjournals.org/content/56/10/1575.abstract
AB Natural killer cells (NKs) are important effectors of the innate immune system, with marked antitumor activity. Imaging NK trafficking in vivo may be relevant to following up the efficacy of new therapeutic approaches aiming at increasing tumor-infiltrating NKs (TINKs). The specific aims of present study were to efficiently target NKs using a 99mTc-anti-CD56 and to image human NK trafficking in SCID mice bearing human cancer. Methods: The anti-CD56 monoclonal antibody (mAb) was radiolabeled with 99mTc, and in vitro quality controls were performed to test labeling efficiency, stability, and binding affinity to CD56. In vivo biodistribution was determined by injecting 5.5 MBq (104 ng) of radiolabeled antibody in the tail vein of SCID mice, which were then sacrificed at 1, 3, 6, and 24 h after injection. Targeting experiments were performed on 2 groups of SCID mice inoculated subcutaneously with increasing numbers of human NKs in the right thigh (from 2.5 × 106 to 40 × 106) and human granulocytes (CD56−) or anaplastic thyroid cancer (ARO) cells in the contralateral thigh as control. TINK trafficking imaging was achieved by injecting 5.5 MBq of 99mTc-anti-CD56 mAb in SCID mice bearing ARO tumor xenografts in the right thigh, 24 h after being reconstituted with 105, 106, or 107 human NKs. Results: Anti-CD56 mAb was radiolabeled, achieving a radiochemical purity of more than 97% and a specific activity of 3,700 MBq/mg and retaining biochemical integrity and binding activity. In vivo studies revealed physiologic uptake in the liver and kidneys. Targeting experiments confirmed the specificity of labeled antibody to CD56+ cells. Human NK cells injected in CD1 nude mice accumulated in the ARO tumors within 24 h and were imaged as early as 3 h after intravenous administration of 99mTc-anti-CD56. Conclusion: 99mTc-anti-CD56 is a promising tool for in vivo imaging of TINK cell trafficking.