Bifunctional HPPH-N2S2-99mTc conjugates as tumor imaging agents: synthesis and biodistribution studies

Abstract

Pyropheophorbide-a and the corresponding 3-(1'-hexyloxyethyl)-3-devinyl derivative ( HPPH ), the tumor-avid photosensitizers were conjugated with mono- or di-bisaminoethanethiols ( N 2 S 2 ligand). The in vivo biodistribution study of the related 99m Tc complexes was performed in F-344 rats bearing Ward colon tumors at 4 h and 24 h post injection. These data show that the complexes are stable and among four tracers, HPPH di-99 m Tc N 2 S 2 conjugate reaches the highest tumor uptake (%ID/g). The larger tumors reach higher concentrations of the tracer. However, the short 6 h half life of 99 m Tc is incompatible with the 24 h imaging time, suggesting that the use of a longer-lived isotope such as 111 In could still provide a useful scanning agent, or that further structure-activity screening could yield an HPPH analog with more appropriate pharmacokinetics for tumor imaging with 99 m Tc .