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

Pyropheophorbide-a and the corresponding 3-(1'-hexyloxyethyl)-3-devinyl derivative (HPPH), the tumor-avid photosensitizers were conjugated with mono- or di-bisaminoethanethiols (N₂S₂ ligand). The in vivo biodistribution study of the related ^99mTc 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- ^99mTc N₂S₂ 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 ^99mTc is incompatible with the 24 h imaging time, suggesting that the use of a longer-lived isotope such as ¹¹¹In 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 ^99mTc.