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.
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.
