The occurence of restenosis following percutaneous transluminal coronary angioplasty is prevented or inhibited using a photopheresis treatment method. In accordance with the photopheresis treatment method, a photoactive compound such as 8-methoxypsoralen is administered to the patient's blood or affected tissue, or some fraction thereof, in vitro or in vivo using conventional administration routes. A portion of the patient's blood or affected tissue is then treated (preferably, extracorporeally) using photopheresis, which comprises subjecting the blood or affected tissue to electromagnetic radiation in a wavelength suitable for activating the photoactive compound, such as ultraviolet light, preferably long wavelength ultraviolet light in the wavelength range of 320 to 400 nm, commonly called UVA light. The treated blood or affected tissue, or a fraction thereof, is returned to the patient (in the case of extracoporeal photopheresis) or remains in the patient (following in vivo photopheresis).

The occurrence of restenosis following percutaneous transluminal coronary angioplasty is prevented or inhibited using a photopheresis treatment method, In accordance with the photopheresis treatment method, a photoactive compound such as 8-methoxypsoralen is administered to the patient's blood or affected tissue, or some fraction thereof, in vitro or in vivo using conventional administration routes. A portion of the patient's blood or affected tissue is then treated (preferably, extracorporeally) using photopheresis, which comprises subjecting the blood or affected tissue to electromagnetic radiation in a wavelength suitable for activating the photoactive compound, such as ultraviolet light, preferably long wavelength ultraviolet light in the wavelength range of 320 to 400 nm, commonly called UVA light. The treated blood or affected tissue, or a fraction thereof, is returned to the patient (in the case of extracorporeal photopheresis) or remains in the patient (following in vivo photopheresis).

A broad class of photosensitive compounds having enhanced in vivo target tissue selectivity and versatility in photodynamic therapy. Many furocoumarin compounds, such as psoralens, exhibit cytostatic activity when photoactivated but exhibit little in vivo specificity for selectively accumulating in any particular target tissue such as atheromatous plaques. Reactive Oxygen Producing Photosensitizers ("ROPPs") are photoactivatable compounds having an affinity for hyperproliferating cells (such as atheromatous plaque cells), which when photoactivated, produce cytotoxic reaction products. The photoactivity of a ROPP, such as a porphyrin, may be reduced by metalating the porphyrin while the selective affinity of the metalized ROPP for hyperproliferating tissue remains substantially unchanged. By linking a furocoumarin compound to a ROPP to form a F-ROPP, the cytostatic properties of the furocoumarin portion of the F-ROPP can be exploited while the selective affinity of the ROPP portion of the compound for hyperproliferating cells such as atheromatous plaque provides enhanced tissue selectivity without cytotoxicity. In vivo, certain F-ROPPs may be forced to selectively accumulate in a target tissue by illuminating only the target tissue with light having a wavelength operable for photoactivating the F portion of the F-ROPP thereby causing the F-ROPP to either form a monoadduct with or crosslink the cellular DNA in the target tissue. Light of a second wavelength can then be delivered to the target tissue to photoactivate the ROPP portion causing further interference with cellular activity.

Levels of psoralen concentration in a biological detection target are determined so that an appropriate UVA light dose of PUVA therapy can be delivered to a biological treatment target. The appropriate therapy is determined by the product of the UVA light dose and psoralen concentration level. After determination of a baseline optical autofluoresence signal from the detection target, a first dosage of psoralen (preferably 8-methoxypsoralen [8-MOP]) is administered. Thereafter, the detection target is irradiated under the same conditions as the pre-psoralen irradiation. Then, the optical return from the psoralen-treated detection target is analyzed. A computer (86) compares the pre-psoralen optical return and psoralen-treated optical return to calculate a real time determination of the concentration level of psoralen in the treatment target. Then, then knowing the precise psoralen concentration level, a UV dosage level required to achieve the desired PUVA therapy can be precisely determined and applied to the treatment target. In some embodiments, the detection target is the treatment target and in vivo real time psoralen concentration is determined. Various forms of applicators (52, 452, 552, 652, 752) are provided for differing types of targets. Each applicator is mounted on an optical fiber bundle (54). In some embodiments, the same optical fiber bundle (54) is employed to transmit the irradiation and optical return signals in the psoralen concentration determination, as well as to transmit the UVA for the PUVA therapy.

A broad class of photosensitive compounds having enhanced in vivo target tissue selectivity and versatility in photodynamic therapy. Many furocoumarin compounds, such as psoralens, exhibit cytostatic activity when photoactivated but exhibit little in vivo specificity for selectively accumulating in any particular target tissue such as atheromatous plaques. Reactive Oxygen Producing Photosensitizers ("ROPPs") are photoactivatable compounds having an affinity for hyperproliferating cells (such as atheromatous plaque cells), which when photoactivated, produce cytotoxic reaction products. The photoactivity of a ROPP, such as a porphyrin, may be reduced by metalating the porphyrin while the selective affinity of the metalized ROPP for hyperproliferating tissue remains substantially unchanged. By linking a furocoumarin compound to a ROPP to form a F-ROPP, the cytostatic properties of the furocoumarin portion of the F-ROPP can be exploited while the selective affinity of the ROPP portion of the compound for hyperproliferating cells such as atheromatous plaque provides enhanced tissue selectivity without cytotoxicity. In vivo, certain F-ROPPs may be forced to selectively accumulate in a target tissue by illuminating only the target tissue with light having a wavelength operable for photoactivating the F portion of the F-ROPP thereby causing the F-ROPP to either form a monoadduct with or crosslink the cellular DNA in the target tissue. Light of a second wavelength can then be delivered to the target tissue to photoactivate the ROPP portion causing further interference with cellular activity.