Multimodality Agents for Tumor Imaging (PET, Fluorescence) and Photodynamic Therapy. A Possible “See and Treat” Approach

Abstract

Methyl 3-(1'-m-iodobenzyloxyethyl)-3-devinylpyropheophorbide-a (2), obtained in a sequence of reactions from pyropheophorbide-a (a chlorophyll-a derivative), was found to be a promising imaging agent and a photosensitizer for photodynamic therapy (PDT). The electrophilic aromatic iodination of the corresponding trimethylstannyl intermediate with Na124I in the presence of an Iodogen bead afforded 124I-labeled photosensitizer 4 with >95% radioactive specificity. In addition to drug-uptake, the light fluence and fluence rate that were used for the light treatment had a significant impact in long-term tumor cure. The iodo photosensitizer 2 (nonlabeled analogue of 4) produced 100% tumor cure (5/5 mice were tumor free on day 60) at a dose of 1.5 micromol/kg and a light dose of 128 J/cm2, 14 mW/cm2 for 2.5 h (lambda(max) 665 nm) at 24 h postinjection. The photosensitizer also showed promising tumor fluorescence and PET imaging ability. Our present work demonstrates the utility of the first 124I-labeled photosensitizer as a "multimodality agent", which could further be improved by using more tumor-avid and/or target-specific photosensitizers.

Contrast-Enhanced MRI-Guided Photodynamic Cancer Therapy with a Pegylated Bifunctional Polymer Conjugate

“…Recently, there has been an increased interest in the use of photosensitizers with in vivo imaging modalities to provide a common system for simultaneous imaging and therapy (11)(12)(13). MRI is a non-invasive imaging modality and has several advantages over other imaging modalities since it provides three-dimensional anatomic images with high spatial resolution.…”

Erythrocytes Membrane Photodestruction Sensitized Chlorophyll a Derivatives: Some Structure-Activity Regularities

“…It was shown that chlorins without exo-cycle (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) cause an active photosensitized lysis of erythrocytes regardless of the substituent's nature. The presence of exocycle (compounds 1-19) in the most cases leads to decrease in photohemolysis power and increase in its induction period.…”

“…[1][2][3][4][5][6] Thus, new PS searching among chlorophyll a derivatives is of a good chance and the investigation of their activity mechanisms and "structure-activity" regularities are of a great interest for new potential PS synthesis planning. [15,21,[28][29][30][31][32] Variation of chlorins chemical structure features such as charge, hydrophobicity and steric properties leads to the significant changing of the pigments ability to insert into the cell which can define their photodynamic effectivity. [33,34] The ability of pigments to interact with membrane structures is of a great significance for photosensitizing activity appearance in cell culture and in vivo.…”

TSPO 18 kDa (PBR) Targeted Photosensitizers for Cancer Imaging (PET) and PDT

“…15 Photodynamic therapy (PDT) is a unique approach that uses low energy light to kill cancer cells; [16][17][18][19][20] more selective and potent sensitizers need to be developed. PET (positron emission tomography) [21][22][23] 25 although the PET imaging result of our 124 I labeled porphyrin photosensitizer was quite decent, we are still trying to find a more breast cancer specific agent for tumor detection and therapy.…”

“…25 Upon reaction with BOP [(benzotriazol-1-yloxy)tris(dimethylamino)-phosphonium hexafluorophosphate] and hexamethylene diamine, 8 was converted into amide 9 in 60% yield. By following a similar approach, after reacting with N-Boc-ethylenediamine, 8 was converted to 10 in 90% yield.…”