Compared to purpurinimides, the pyropheophorbide containing an iodobenzyl group showed enhanced PDT efficacy and tumor imaging (124I-PET) ability.
Two positional isomers of purpurinimide, 3-[1'-(3-iodobenzyloxyethyl)] purpurin-18-N-hexylimide methyl ester 4, in which the iodobenzyl group is present at the top half of the molecule (position-3), and a 3-(1'-hexyloxyethy)purpurin-18-N-(3-iodo-benzylimide)] methyl ester 5, where the iodobenzyl group is introduced at the bottom half (N-substitued cyclicimide) of the molecule, were derived from chlorophyll-a. The tumor uptake and phototherapeutic abilities of these isomers were compared with the pyropheophorbide analogue 1 (lead compound). These compounds were then converted into the corresponding 124I-labeled PET imaging agents with specific activity >1 Ci/micromol. Among the positional isomers 4 and 5, purpurinimide 5 showed enhanced imaging and therapeutic potential. However, the lead compound 1 derived from pyropheophorbide-a exhibited the best PET imaging and PDT efficacy. For investigating the overall lipophilicity of the molecule, the 3-O-hexyl ether group present at position-3 of purpurinimide 5 was replaced with a methyl ether substituent, and the resulting product 10 showed improved tumor uptake, but due to its significantly higher uptake in the liver, spleen, and other organs, a poor tumor contrast in whole-body tumor imaging was observed.
Pandey
Suresh K
SK
PDT Center, Cell Stress Biology and Department of Dermatology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
Sajjad
Munawwar
M
Chen
Yihui
Y
Pandey
Anupam
A
Missert
Joseph R
JR
Batt
Carrie
C
Yao
Rutao
R
Nabi
Hani A
HA
Oseroff
Allan R
AR
Pandey
Ravindra K
RK
D000818:Animals; D000880:Anthraquinones / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002734:Chlorophyll / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000077194:Chlorophyll A; D007457:Iodine Radioisotopes / Q000737:chemistry; D007462:Iodobenzenes / Q000737:chemistry*; D007536:Isomerism; D051379:Mice; D009369:Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D049268:Positron-Emission Tomography; D014018:Tissue Distribution
D000880:Anthraquinones; D007457:Iodine Radioisotopes; D007462:Iodobenzenes; D017319:Photosensitizing Agents; D002734:Chlorophyll; C031905:iodobenzene; C511975:purpurin anthraquinone; D000077194:Chlorophyll A