Bifunctional HPPH-N2S2-Tc-99m 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 Tc-99m complexes was performed in F344 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-Tc-99m 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 Tc-99m is incompatible with the 24 h imaging time, suggesting that the use of a longer-lived isotope such as In-111 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 Tc-99m. Copyright (C) 2003 Society of Porphyrins & Phthalocyanines.