PET imaging of soluble yttrium-86-labeled carbon nanotubes in mice.
BACKGROUND
The potential medical applications of nanomaterials are shaping the landscape of the nanobiotechnology field and driving it forward. A key factor in determining the suitability of these nanomaterials must be how they interface with biological systems. Single walled carbon nanotubes (CNT) are being investigated as platforms for the delivery of biological, radiological, and chemical payloads to target tissues. CNT are mechanically robust graphene cylinders comprised of sp(2)-bonded carbon atoms and possessing highly regular structures with defined periodicity. CNT exhibit unique mechanochemical properties that can be exploited for the development of novel drug delivery platforms. In order to evaluate the potential usefulness of this CNT scaffold, we undertook an imaging study to determine the tissue biodistribution and pharmacokinetics of prototypical DOTA-functionalized CNT labeled with yttrium-86 and indium-111 ((86)Y-CNT and (111)In-CNT, respectively) in a mouse model.


RESULTS
The (86)Y-CNT construct was synthesized from amine-functionalized, water-soluble CNT by covalently attaching multiple copies of DOTA chelates and then radiolabeling with the positron-emitting metal-ion, yttrium-86. A gamma-emitting (111)In-CNT construct was similarly prepared and purified. The constructs were characterized spectroscopically, microscopically, and chromatographically. The whole-body distribution and clearance of yttrium-86 was characterized at 3 and 24 hours post-injection using positron emission tomography (PET). The yttrium-86 cleared the blood within 3 hours and distributed predominantly to the kidneys, liver, spleen and bone. Although the activity that accumulated in the kidney cleared with time, the whole-body clearance was slow. Differential uptake in these target tissues was observed following intravenous or intraperitoneal injection.


CONCLUSIONS
The whole-body PET images indicated that the major sites of accumulation of activity resulting from the administration of (86)Y-CNT were the kidney, liver, spleen, and to a much less extent the bone. Blood clearance was rapid and could be beneficial in the use of short-lived radionuclides in diagnostic applications.
McDevitt
Michael R
MR
Molecular Pharmacology and Chemistry Department, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America. m-mcdevitt@ski.mskcc.org
Chattopadhyay
Debjit
D
Jaggi
Jaspreet S
JS
Finn
Ronald D
RD
Zanzonico
Pat B
PB
Villa
Carlos
C
Rey
Diego
D
Mendenhall
Juana
J
Batt
Carl A
CA
Njardarson
Jon T
JT
Scheinberg
David A
DA
D000818:Animals; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D008297:Male; D051379:Mice; D008819:Mice, Nude; D046529:Microscopy, Electron, Transmission; D037742:Nanotubes, Carbon; D049268:Positron-Emission Tomography; D012995:Solubility; D013059:Spectrum Analysis, Raman; D014018:Tissue Distribution; D015021:Yttrium Radioisotopes / Q000737:chemistry* / Q000493:pharmacokinetics
D037742:Nanotubes, Carbon; D015021:Yttrium Radioisotopes