99mTc-labeled superparamagnetic iron oxide nanoparticles for multimodality SPECT/MRI of sentinel lymph nodes.
The purpose of this study was to develop multimodality SPECT/MRI contrast agents for sentinel lymph node (SLN) mapping in vivo.


METHODS
Nanoparticles with a solid iron oxide core and a polyethylene glycol coating were labeled with (99m)Tc. The labeling efficiency was determined with instant thin-layer chromatography and magnetic separation. The stability of the radiolabeled superparamagnetic iron oxide nanoparticles (SPIONs) was verified in both sterile water and human serum at room temperature 6 and 24 h after labeling. Five Wistar rats were injected subcutaneously in the right hind paw with (99m)Tc-SPIONs (25-50 MBq, ∼0.2 mg of Fe) and sacrificed 4 h after injection. Two animals were imaged with SPECT/MRI. All 5 rats were dissected; the lymph nodes, liver, kidneys, spleen, and hind paw containing the injection site were removed and weighed; and activity in the samples was measured. The microdistribution within the lymph nodes was studied with digital autoradiography.


RESULTS
The efficiency of labeling of the SPIONs was 99% 6 h after labeling in both water and human serum. The labeling yield was 98% in water and 97% in human serum 24 h after labeling. The SLN could be identified in vivo with SPECT/MRI. The accumulation of (99m)Tc-SPIONs (as the percentage injected dose/g [%ID/g]) in the SLN was 100 %ID/g, whereas in the liver and spleen it was less than 2 %ID/g. Digital autoradiography images revealed a nonhomogeneous distribution of (99m)Tc-SPIONs within the lymph nodes; nanoparticles were found in the cortical, subcapsular, and medullary sinuses.


CONCLUSIONS
This study revealed the feasibility of labeling SPIONs with (99m)Tc. The accumulation of (99m)Tc-SPIONs in lymph nodes after subcutaneous injection in animals, verified by SPECT/MRI, is encouraging for applications in breast cancer and malignant melanoma.
Department of Medical Radiation Physics, Lund University, Lund, Sweden. Renata.Madru@med.lu.se
Renata
R
Madru
Pontus
P
Kjellman
Fredrik
F
Olsson
Karin
K
Wingårdh
Christian
C
Ingvar
Freddy
F
Ståhlberg
Johan
J
Olsrud
Jimmy
J
Lätt
Sarah
S
Fredriksson
Linda
L
Knutsson
Sven-Erik
SE
Strand
D000818:Animals; D002855:Chromatography, Thin Layer; D003287:Contrast Media; D005290:Ferric Compounds / Q000493:pharmacokinetics; D007091:Image Processing, Computer-Assisted; D008198:Lymph Nodes / Q000000981:diagnostic imaging* / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008280:Magnetics; D058185:Magnetite Nanoparticles; D008297:Male; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles; D010316:Particle Size; D014677:Pharmaceutical Vehicles; D011092:Polyethylene Glycols; D011786:Quality Control; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D021701:Sentinel Lymph Node Biopsy / Q000379:methods*; D013667:Technetium / Q000493:pharmacokinetics; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
D003287:Contrast Media; D005290:Ferric Compounds; D058185:Magnetite Nanoparticles; D014677:Pharmaceutical Vehicles; D019275:Radiopharmaceuticals; C000499:ferric oxide; D011092:Polyethylene Glycols; D013667:Technetium