aluminum-tetrasulfophthalocyanine and Prostatic-Neoplasms

Sulfonated aluminum phthalocyanines (AlPcS) are potent photosensitizers for the photodynamic therapy (PDT) of cancer. In this study we evaluate the possibility to improve the efficacy of AlPcS-PDT for prostate cancer by targeting tetrasulfonated aluminum phthalocyanines (AlPcS(4)) to the gastrin-releasing peptide receptor (GRPR) through coupling to bombesin. A mono-carbohexyl derivative of AlPcS(4) is attached to 8-Aoc-bombesin(7-14)NH(2) via an amide bridge to yield a bombesin-AlPcS(4) conjugate linked by a C-14 spacer chain. The conjugate is characterized by mass spectroscopy and shown to bind to the GRPR with a relative binding affinity (RBA) of 2.3, taking bombesin (RBA=100) as unity. The in vitro photodynamic efficacy of the conjugate against PC-3 human prostate cancer cells is improved by a factor 2.5 over the non-conjugated mono-carbohexyl derivative of AlPcS(4).

Topics: Binding Sites; Bombesin; Cell Line, Tumor; Drug Delivery Systems; Humans; Indoles; Male; Mass Spectrometry; Organometallic Compounds; Photochemotherapy; Photosensitizing Agents; Prostatic Neoplasms; Receptors, Bombesin

Variations in the optical coefficients in tissue and the photosensitizer during photodynamic therapy (PDT) will require adjustment of the light dose during the course of therapy. We have studied the dynamics using light transmission spectra for two different tumor models when tetrasulfonated aluminum phthalocyanine (AlPcS4) was used as photosensitizer.. Spectra were measured noninvasively in the EMT6/Ed murine tumor model, and with interstitially implanted source and probe fibers in the Dunning R3327-AT rat tumor model. Measurements were performed in the range 600-840 nm, using a tunable dye laser, a diode laser, and a Ti:Sapphire laser. AlPcS4 has absorption in the range 600-700 nm with an absorption peak at 670 nm in saline.. The in vivo spectrum of AlPcS4 both in the EMT6/Ed tumor model and the Dunning R3327-AT tumor model differs from the spectrum of AlPcS4 in saline. The absorption at 670 nm was reduced, whereas the absorption at 640 nm increased. Exposure of phototherapeutic levels of light caused reduced light absorption by the photosensitizer and further spectral shift.. We found that the AIPcS4 absorption spectrum changes in a biological environment, and we also observed increased light transmission at the treatment wavelength during PDT in both tumor models. Instability in the absorption spectrum of the photosensitizer may influence the effectiveness of PDT.

Topics: Animals; Antineoplastic Agents; Indoles; Lasers; Male; Mice; Neoplasm Transplantation; Neoplasms, Experimental; Organometallic Compounds; Phantoms, Imaging; Photochemotherapy; Prostatic Neoplasms; Radiation-Sensitizing Agents; Rats; Spectrometry, Fluorescence; Spectrophotometry; Tumor Cells, Cultured