Photoangioplasty for Human Peripheral Atherosclerosis

Rockson, Stanley G.; Kramer, Paul H.; Razavi, Mahmood K.; Szuba, Andrzej; Filardo, Steven D.; Fitzgerald, Peter J.; Cooke, John P.; Yousuf, Shuja; DeVault, Arthur R.; Renschler, Markus F.; Adelman, Daniel C.

doi:10.1161/01.cir.102.19.2322

Cited by 89 publications

(32 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Currently this investigational drug is in a multi-center Phase II randomized trial for the photoangioplastic treatment of peripheral arterial disease (PAD) [55][56][57]. A Phase I trial has also been initiated recently for the photoangioplastic reduction of coronary arterial disease (CAD).…”

Section: Antrinmentioning

confidence: 99%

“…In this trial, a standard dose escalation study, the ANTRIN 1 PA procedure consisted of: (1) administering the drug via an intravenous injection (1-5 mg kg À1 ), (2) waiting until 24 h post-injection (to allow for a maximized uptake of the drug in the diseased plaque with concomitant enhanced clearance from the plasma), and (3) illumination of the diseased site with 732 nm red-light delivered via an intravascular fiberoptic catheter. Varying light fluences were used, namely, 400, 500, 625, or 781 J cm À1 fiber [55,56,59]. Serial quantitative angiography and intravascular ultrasound (IVUS) analyses allowed for an objective assessment of the vascular responses.…”

Section: Antrinmentioning

confidence: 99%

“…Importantly, no adverse vascular responses were seen by angiography 28 days after treatment of ANTRIN 1 PA. Furthermore, no evidence of ANTRIN 1 -related vascular damage, thrombus, hemorrhage, dissection, or deleterious effects on normal vessel walls were observed at any point, at or below the MTD (maximum tolerated dose) by IVUS [57,60]. Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly.…”

Section: Antrinmentioning

confidence: 99%

See 2 more Smart Citations

Texaphyrins: a new approach to drug development

Mody

Sessler

2001

J. Porphyrins Phthalocyanines

View full text Add to dashboard Cite

ABSTRACT:The texaphyrins are prototypical metal-coordinating expanded porphyrins. They represent a burgeoning class of pharmacological agents that show promise for an array of medical applications. Currently, two different water-soluble lanthanide texaphyrins, namely motexafin gadolinium (Gd-Tex, 1) and motexafin lutetium (Lu-Tex, 2), are involved in multi-center clinical trials for a variety of indications. The first of these agents, XCYTRIN 1 (motexafin gadolinium) Injection, is being evaluated as a potential X-ray radiation enhancer in a randomized Phase III clinical trial in patients with brain metastases. The second, in various formulations, is being evaluated as a photosensitizer for use in: (i) the photodynamic treatment of recurrent breast cancer (LUTRIN KEYWORDS: texaphyrin; porphyrin; expanded porphyrin; motexafin gadolinium; motexafin lutetium; photodynamic therapy; photoangioplasty; photosensitizer; radiation sensitization; breast cancer; age-related macular degeneration THE CHEMISTRY OF TEXAPHYRINS OverviewThe texaphyrins, represented by prototypic complexes 1 and 2 (motexafin gadolinium, Gd-Tex and motexafin lutetium, Lu-Tex, respectively, cf. Fig. 1), are aromatic tripyrrolic, pentaaza, Schiff-base macrocycles that bear a strong, but 'expanded' resemblance to the porphyrins and other naturally occurring tetrapyrrolic prosthetic groups [1][2][3]. For instance, like the porphyrins, the texaphyrins are fully aromatic and intensely colored. They are, however, dark green (rather than purplish), and in terms of their aromatic peripheries are formally 22 p-electron systems rather than 18 p-electron ones. As a consequence, they display Sorettype absorption bands (high energy transitions) at ca 470 nm (vs 400-410 nm for porphyrins) and a lowest energy Q-type absorption band at b700 nm (vs ca 620 nm for porphyrins), with the exact wavelengths of the latter transition primarily depending on the substituents on the benzene moiety and the metal ion complexed within the macrocyclic core (see Fig. 2). Also, in contrast to porphyrins, the texaphyrins are monoanionic ligands that contain five, rather than four, coordinating nitrogen atoms within their central core [1,4]. The fact that this central core is roughly 20% larger than that of the porphyrins further endows the texaphyrins with an ability to form stable, nonlabile 1:1 complexes with a range of larger metal cations, including specifically those of the trivalent lanthanide series [5]. In fact, now almost 12 years after their original invention, the texaphyrins (e.g 1 and 2) remain the only well-characterized expanded porphyrin systems for which an extensive 'large cation' coordination chemistry exists [1,5,6].Among the metals that form stable complexes with texaphyrins are lanthanide(III), cadmium(II), yttrium(III), and manganese(II) [1,6]. Of these cations, cadmium(II) was the first that was found to give an acceptable yield ($25%) of the desired Cd(II) texaphyrin complex 3 [1,4]. Subsequently, the critical oxidative-metallation reaction required to prepar...

show abstract

Section: Antrinmentioning

confidence: 99%

Section: Antrinmentioning

confidence: 99%

Section: Antrinmentioning

confidence: 99%

See 1 more Smart Citation

Texaphyrins: a new approach to drug development

Mody

Sessler

2001

J. Porphyrins Phthalocyanines

View full text Add to dashboard Cite

show abstract

“…In particular, porphyrinic pigments have enjoyed widespread use as photodynamic therapy (PDT) agents in the treatment of cancers, age-related macular degeneration, [1][2][3] and most recently, cardiovascular disease. [4,5] Unfortunately, the therapeutic window of many agents is small, and the associated toxicity can be significant. [6] Over time, a number of modifications have been made to the porphyrins to increase their singlet oxygen quantum yields, make them more water soluble, improve their pharmacokinetics, and target them to tissues of interest.…”

Section: Introductionmentioning

confidence: 99%

Model Systems for Fluorescence and Singlet Oxygen Quenching by Metalloporphyrins

McCarthy

Weissleder

2007

ChemMedChem

View full text Add to dashboard Cite

Next-generation photodynamic therapy agents will minimize extraneous phototoxicity by being active only at the target site. To this end, we have developed a model system to systematically investigate the excited-state quenching ability of a number of metalloporphyrins. Central metal ions that prefer four-coordinate, square planar orientations (Ag(II), Cu(II), Ni(II), Pd(II), and Zn(II)) were used. Porphyrin dimers based on 5-(4-aminophenyl)-10,15,20-triphenylporphyrin and comprising both a free base porphyrin and a metalloporphyrin covalently linked through a five-carbon alkyl chain were synthesized. The fluorescence and singlet oxygen quantum yields for the dimers were probed at 630 and 650 nm, respectively, resulting in the excitation of only the free base porphyrin and allowing a comparison of the quenching efficacy of each central metal ion. These results demonstrate that metalloporphyrins can serve as efficient quenchers, and may be useful in the design of novel light-activated therapeutic agents.

show abstract

“…The application of Antrin, followed by endovascular photoactivation, termed photoangioplasty, has just completed a phase I safety study in patients with peripheral arterial disease [8]. Currently, Antrin is being evaluated in a phase II peripheral study and also in a phase I clinical study for the treatment of primary atherosclerosis and also the prevention of restenosis involving coronary arteries.…”

Section: Introductionmentioning

confidence: 99%

Photodynamic therapy using motexafin lutetium in allograft coronary artery disease

Woodburn

Rodriguez

Robbins

et al. 2001

J. Porphyrins Phthalocyanines

View full text Add to dashboard Cite

Graft coronary artery disease (GCAD) limits long-term patient survival following heart transplantation. There are few treatment options. Exploration into less invasive diagnostic techniques and attenuation of allograft coronary disease is warranted. The selectivity of Antrin 1 Injection (a motexafin lutetium sensitizer, Lu-Tex) and illumination with far-red light, approximately 732 nm, has been evaluated in several preclinical atherosclerosis models. Lu-Tex, using fluorescence microscopy, was found to partition into distinct punctate cytoplasmic compartments in cultured human bypass coronary smooth muscle cells (SMCs). Using specific organelle probes the chief subcellular localization sites were lysosomes and endoplasmic reticulum. The inhibitory effect of Lu-Texmediated photoactivation was demonstrated using SMCs; many cells died via an apoptotic pathway. Following illumination, fluorescence microscopy revealed sensitizer redistribution with fluorescence being observed in the mitochondria. The distribution of Lu-Tex was evaluated in a rat model of heterotopic cardiac allografts 60 days after transplantation. Lu-Tex was retained in the cardiac allograft, exhibiting a five-fold increase in retention between the allograft and native heart. These results encourage further exploration of Lu-Tex for diagnosis, and possible amelioration of chronic graft vascular disease using photodynamic therapy.

show abstract

Photoangioplasty for Human Peripheral Atherosclerosis

Abstract: This phase I study demonstrates that photoangioplasty with motexafin lutetium is well tolerated and safe. Preliminary efficacy data suggest a future role for the treatment of flow-limiting atherosclerosis.

Cited by 89 publications

References 5 publications

Texaphyrins: a new approach to drug development

Texaphyrins: a new approach to drug development

Model Systems for Fluorescence and Singlet Oxygen Quenching by Metalloporphyrins

Photodynamic therapy using motexafin lutetium in allograft coronary artery disease

Contact Info

Product

Resources

About