Monitoring of a new approach of immunotherapy with allogenic (111)In-labelled NK cells in patients with renal cell carcinoma.
The transfusion of allogenic, in vitro expanded natural killer cells (NKC) is a novel therapy option in oncology. To date, however, the biodistribution and kinetics of allogenic NKC have not been investigated. Therefore, in this study three patients with renal cell carcinoma received 3-7 x 10(8) NKC labelled with indium-111 oxine with a tenfold excess of unlabelled cells during NKC therapy. Whole-body scintigrams were obtained (0.5-144 h) in the anterior and posterior views. Scintigrams were analysed using a region of interest technique, and single-photon emission tomography (SPET) studies of the abdomen were performed. Results were compared to those obtained with polymerase chain reaction (PCR) of the peripheral blood (determination of foreign DNA, nested PCR, limit of detection 0.01%). Shortly after transfusion of NKC, more than 50% of the activity was accumulated in the lungs. We observed redistribution effects from lungs to liver, spleen and bone marrow. No significant loss of activity could be detected. In two of four large metastases, tracer accumulation could be proven by SPET. As confirmed by scintigrams and PCR, the fraction of circulating transfused cells was low at all times. Long-term activity retention might be caused either by survival of the allogenic cells, as confirmed by PCR (up to 3 days p.i.), or by phagocytosis of labelled cellular fragments. However, PCR data and uptake in metastases indicated long survival of a portion of allogenic NKC. Such long survival and low retention of the cells in the lung are requirements for an effective immunotherapeutic approach.
Meller
Birgit
B
Clinic of Radiotherapy and Nuclear Medicine, University of Lübeck, Lübeck, Germany. meller@stnuk.uni-luebeck.de
Frohn
Christoph
C
Brand
Jörg-Matthias
JM
Lauer
Isabel
I
Schelper
Lutz F
LF
von Hof
Katharina
K
Kirchner
Holger
H
Richter
Eckart
E
Baehre
Manfred
M
D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000000981:diagnostic imaging* / Q000276:immunology / Q000628:therapy*; D002470:Cell Survival; D017690:Cell Transplantation / Q000379:methods; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007205:Indium Radioisotopes; D007680:Kidney Neoplasms / Q000000981:diagnostic imaging / Q000276:immunology / Q000628:therapy; D007694:Killer Cells, Natural / Q000000981:diagnostic imaging* / Q000637:transplantation*; D008875:Middle Aged; D009928:Organ Specificity; D016133:Polymerase Chain Reaction / Q000379:methods; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution; D014184:Transplantation, Homologous / Q000379:methods
D007205:Indium Radioisotopes; D019275:Radiopharmaceuticals