Intravenously administered, multi-walled carbon nanotubes functionalized with diethylentriaminepentaacetic dianhydride (DTPA-MWNT) and radiolabeled with Indium-111 (111In), were dynamically tracked in vivo using a microSingle Photon Emission Tomography (microSPECT) scanner. Imaging showed that nanotubes enter the systemic blood circulation and within

5 min begin to permeate through the renal glomerular filtration system into the bladder. Urinary excretion of DTPA-MWNT was confirmed at 24 h post-administration. The renal clearance of DTPA-MWNT in rats reported here opens the door to the use of MWNT as components of multiple diagnostic and therapeutic modalities in development for systemic indications such as cardiovascular diseases and cancer. There has been an explosive increase in the number of nanomaterials designed for biomedical applications that has generated extraordinary interest and expectations for effective, disease-eradicating therapeutic modalities.[1] At the same time, the toxicological burden and the pharmacological viability of such novel nanomaterials remain largely unknown, further complicating the discussion for the need of a new regulatory framework for nanomaterials.[2] One such type of highly innovative nanomaterials is the CNT, first reported in the early 1990s by Iijima.[3] Extraordinary characteristics of this material, consisting only of a network of carbon atoms in the nanometer scale, include great tensile strength, as well as high electrical and thermal conductivity.[4] Our work has focused on the pharmacological development of functionalized CNT (f-CNT) using the 1, 3-dipolar cycloaddition reaction [5] to render the CNT surfaces water-soluble and therefore compatible with the biological milieu. Various biomedical applications of f-CNT have been explored and encouraging proof-of-principle studies have indicated their effective role as delivery systems for genes, peptides, antimicrobial agents and cytotoxic drug molecules.[6] However, the clinical evaluation of any therapeutic or diagnostic agent based on f-CNT will involve the administration or implantation of nanotubes and their matrices into patients. In order to design such clinical studies, preclinical development of f-CNT is essential, particularly the determination of their in vivo pharmacological profiles. Towards that goal we first reported tissue biodistribution and blood circulation half-life data following intravenous administration of single-walled CNT (SWNT) covalently functionalized with tracer radionuclides.[7] Other laboratories have also carried out similar in vivo studies following intraperitoneal,[8] intratumoral [9] or intravenous [10] administration of different types of CNT. A very recent report [11] using the functionalization chemistry developed in our laboratories to conjugate monoclonal antibodies for tumor cell targeting of SWNT, also reported rapid, high levels of elimination of the nanotubes, in good agreement with our original observations.[7] However, none of these reports elucidated the