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A Radiopharmaceutical Kit for PET Renography

Hariprasad Gali, Ph.D.

Principal Investigator

Agency: OCAST

Abstract

Renal diseases affect over 26 million American adults. Improved diagnostic techniques that provide physicians with an accurate disease status and the underlying cause are needed to implement appropriate preventive and/or treatment strategies in a timely manner to prevent eventual kidney failure. Renography is an important diagnostic test to manage renal patients. It allows physicians to visualize the kidneys and determine their function. However, currently used imaging technology for renography provides limited information on the renal pathophysiology, which is essential to knowing the underlying cause of the disease. This problem could be overcome by using positron emission tomography (PET), but no suitable radiopharmaceutical is available for using PET for renography. The goal of this project is to prove the feasibility of developing the needed radiopharmaceutical for use in PET renography.

We have completed preliminary research that has identified para-[18F]fluorohippurate (F-18 PFH) as a potential PET renal agent. Structurally, F-18 PFH is a close analog of ortho-[131I]iodohippurate (Hippuran), a discontinued radiopharmaceutical (because iodine-131 is a beta-emitter and its nuclear properties are not suitable for imaging) historically regarded as a gold standard for renography. The image quality obtained from F-18 PFH PET renography in healthy rats was remarkably better than that obtained with Tc-99m MAG3 (a clinical agent) renography. A key advantage of PET renography is that it provides temporal 3-D and slice-specific images of renal parenchyma and quantitative data without additional studies. However, clinical use of F-18 PFH is challenging, as it is prepared by a time-consuming, multi-step radiosynthetic strategy. We therefore propose to develop a new PET renal agent that can be reconstituted from an instant kit with gallium-68 (half-life of 68 minutes) eluted from a generator, which significantly reduces overall cost of the radiopharmaceutical.

For this project we propose to demonstrate 1) the feasibility of producing a dose of the new radiopharmaceutical within 10-20 minutes to minimize loss due to Ga-68 decay, 2) that the biological properties and renogram parameters of the new radiopharmaceutical are suitable for renography, and 3) the proof of concept of our technology to detect renal injury in a rat model of cisplatin-induced nephrotoxicity. The success of this project will lead to a larger project focused on developing chemistry and manufacturing controls (CMCs) and demonstrating safety (preclinical toxicology and radiation dosimetry), as required by FDA for an IND application for conducting Phase 1 clinical trials. The ultimate project goal is to develop an economical and readily accessible radiopharmaceutical for PET renography in patients with renal diseases.