Localisation of [131I]MIBG in nude mice bearing SK-N-SH human neuroblastoma xenografts: effect of specific activity.
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1996-05
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Abstract
The biodistribution of no-carrier-added (n.c.a.) meta-[131I]iodobenzylguanidine ([131I]MIBG) and that prepared by the standard isotopic exchange method were compared in athymic mice bearing SK-N-SH human neuroblastoma xenografts. No advantage in tumour uptake was observed for the n.c.a. preparation. BALB/c nu/nu mice exhibited lower uptake in highly innervated normal tissues (heart and adrenals) than normal BALB/c mice. In another experiment, the distribution of n.c.a. [131I]MIBG in the absence or presence (3-9 micrograms) of MIBG carrier was determined. At both 4 h and 24 h, the heart uptake was reduced by a factor of 1.5 even at a dose of 3 micrograms MIBG. Tumour uptake was not significantly altered by various amounts of unlabelled MIBG at either time point.
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Ganesan Vaidyanathan
Dr. Vaidyanathan is a professor in the Department of Radiology. He is a member of the Nuclear Medicine track of the Medical Physics Graduate Program. His research involves development of radiopharmaceuticals especially for oncologic applications. Some of the projects he is involved in are given below.
I. New methods of radiohalogenating antibodies and its variants
a) Development of newer residualizing agents for the radiohalogenation of internalizing monoclonal antibodies.
b) Development of fluorine-18 labeled residualizing agents for labeling nanobodies.
c) Pre-targeting approach via bioorthogonal chemistry for in vivo labeling of antibodies and nanobodies with 18F and 211At.
d) Methods to label antibodies pre-conjugated with a prosthetic group of the tin precursor of residualizing agents.
e) Multimodal prosthetic groups for labeling antibodies and peptides with multiple radioisotopes.
II. MIBG Analogs for PET imaging
Radioiodinated MIBG is used in the diagnosis of the pathophysiology of the heart as well as neuroendocrine tumors such as neuroblastoma (NB). Design and development of newer fluorine-18 labeled MIBG analogues useful in the PET imaging of NB as well as that of myocardial diseases.
III. Noninvasive Imaging of Alkylguanine-DNA alkyltransferase (AGT)
AGT is a DNA repair protein and is primarily responsible for drug resistance in alkylator chemotherapy. An inverse correlation has been established between the tumor AGT content and the therapeutic outcome. The amount of AGT varies from tumor to tumor and within a group of patients of similar cancer. Thus, it is important to quantify tumor AGT of individual patients before administering alkylator chemotherapy. Our goal is to develop radiolabeled agents with which AGT can be quantified in a noninvasive manner by PET or SPECT imaging.
IV. PSMA targeting for prostate cancer therapy
Development of At-211 labeled urea-based inhibitor of Prostate-specific membrane antigen.
Stephen Thomas Keir
Brain Tumors, Preclinical Testing, Translational Research
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