Ganesan Vaidyanathan, PhD

Professor in Radiology

Department / Division
Radiology / Radiology - General

Address:
Box 3808 Med Ctr
Radiology
Durham, NC 27710

Office Telephone:
(919) 684-7811

Training:

• PhD, University of Kentucky at Lexington, 1987

Research Interests:
I. Noninvasive Imaging of Alkylguanine-DNA alkyltransferase (AGT)

AGT is a DNA repair protein and is primarily responsible for drug resistance in alkylatro 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 positron emission tomography or single photon emission tomography.

II. MIBG Analogs

Design and development of newer analogs of the radiopharmaceutical, meta-iodobenzylguanidine. The goal is to develop an agent which will give better tumor-to-normal tissue ratios. Efforts are under way to introduce various substituents such as nitro, halo and sulfonic onto the benzene ring of MIBG resulting in derivatives with a wide spectrum of lipophilicity. An analog of MIBG in which the benzene ring is replaced by a pyridine ring will also be synthesized. These newer analogs will be evaluated in detail in vitro using various neuroblastoma, pheochromocytoma and medulloblastoma cell lines. Interesting compound(s) will be further evaluated in vivo in normal mice and mice hosting neuroblastoma and medulloblastoma xenografts. Use of various interventional agents to maximize tumor-to-normal tissue ratios will also be investigated.

III. New Methods of Radiohalogenating Antibodies

Efforts are under way in developing an agent with which antibodies can be radioiodinated using a kit formulation yet resulting in minimal in vivo dehalogenation. Other work involves a) development of radiohalogenating agents for antibodies which internalizes and b) conjugation of MIBG to antibodies.

IV. Radiolabeled Octreotide Analogs

Octreotide analogs radiolabeled with 111In and copper isotopes have been reported as potential agents for the diagnosis and treatment of somatostatin receptor positive tumors. Four analogs of octreotide that can be labeled with radioiodine and astaine has ben developed and are undergoing preliminary in vitro and invivo evaluations.

V. IUdR Analogs

5-Iodo-deoxyuridine (IUdR), a thymidine analog, is a DNA seeking agent. Therapeutic potential of IUdR labeled with 125I has been demonstrated. Recently we developed an IUdR analog labeled with the à-emitting nuclide, 211At (AUdR). AUdR has been demonstrated to be several fold more toxic than IUdR in vitro. Both IUdR and AUdR are not very stable in vivo. A 2'-fluorine substituted analog of IudR, FIAU has ben shown to be more stable than the parent compound. A method for the no-carrier-added synthesis radioiodinated FIAU and its astatinated analog has been developed. In vitro and in vivo of evaluation of these analogs are under way.

VI. PSMA targeting for prostate cancer therapy

Development of At-211 labeled urea-based inhibitor of Prostate-specific membraned antigen.