SBIR-STTR Award

The objective is development of a rationally designed 99mTc-peptide radiopharmaceutical for scintigraphic detection and localization of infection/inflammation foci. The designed peptide is based on tuftsin, a tetrapeptide that is a natural component of the immune response network. Binding of tuftsin to its specific receptor on macrophages and granulocytes stimulate phagocytosis. Receptor-tuftsin complex is reported to internalize. A 99mTc-labeled tuftsin molecule is therefore an ideal candidate as an in vivo inflammation imaging agent for any site of active recruitment of macrophages and granulocytes. The initial 99mTc binding peptide we have designed has high affinity for tuftsin receptor (KD, 1-5 nM), is metabolically stable, and has proved promising as an infection/inflammation localizing agent in experimental animals. In Phase I we plan to optimize the peptide formulation as a lyophilized one step labeling kit, study its 99mTc labeling profiles, determine its specificity and affinity for tuftsin receptors on leukocytes, and perform extensive animal studies in mice, rats and rabbits for imaging inflammation foci, clearance patterns, and biodistribution. Phase II will include extended animal studies, product formulation and manufacturing protocols, acute toxicity studies and initiation of preliminary human studies.Proposed commercial application:Tc-Tuftsin analogue has significant potential application in diagnostic nuclear medicine, for imaging of suspected sites of infection and inflammation, including diagnosis of fevers of unknown origin, appendicitis, and AIDS opportunistic infections.National Institute of Allergy and Infectious Diseases (NIAID)

The objective is development of a rationally designed 99mTc-peptide radio- pharmaceutical for scintigraphic detection and localization of infection/ inflammation foci. The designed peptide is based on natural tetrapeptide tuftsin, a component of immune response network. Binding of tuftsin to its candidate as an in vivo inflammation imaging agent for a site of active granulocyte recruitment. Rationally designed tuftsin analogs, based on a newly developed concept of designing receptor-specific radio- pharmaceuticals, will be used in Phase II studies. The design incorporates a type of pro-drug approach in which a tuftsin receptor-specific sequence turns biologically active only upon its complexation with 99mTc metal ion that fixes its bioactive structure. Phase I studies have established 2000 fold higher affinity for a Tc-labeled peptide than that of the unlabeled peptide, based on competitive inhibition studies. This approach thus yields preparations that are functionally carrier-free, thereby, promising high specific activity of the 99mTc-labeled species. In Phase-II, product manufacture, formulation, 99mTc-labelings, acute toxicity studies, extended animals studies and initiation of preliminary human studies will be performed with emphasis on dosimetry, pharmacokinetics and clinical efficacy of the agent in imaging inflammation foci in patients with suspected infection/inflammation. PROPOSED COMMERCIAL APPLICATION: 99mTc-Tuftsin analog has potential applications in diagnostic nuclear medicine for rapid imaging of suspected sites of infection and inflammation, including diagnosis of fevers of unknown origin, appendicitis, prosthetic infections, osteomyelitis, and opportunistic infections.

Thesaurus Terms:
bioimaging /biomedical imaging, contrast media, drug design /synthesis /production, inflammation, oligopeptide, radiopharmacology, technetium disease model, infection, pharmacokinetics, radiation dosage dog