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Motexafin lutetium

Description of motexafin lutetium: motexafin lutetium is a pentadentate aromatic metallotexaphyrin with photosensitizing properties. Motexafin lutetium preferentially accumulates in tumor cells due to their increased rates of metabolism and absorbs light, forming an extended high energy conformational state that produces high quantum yields of singlet oxygen, resulting in local cytotoxic effects. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus)

Current developer:    Pharmacycs, Inc.

Motexafin lutetium is a texaphyrin, marketed as Antrin by Pharmacyclics Inc.  It is a photosensitiser for use in photodynamic therapy to treat skin conditions and superficial cancers. It has also been tested for use in photoangioplasty (photodynamic treatment of diseased arteries). It is photoactivated by 732 nm light which allows greater depth of penetration.

Highlight on recent research using Motexafin lutetium

1. Motexafin lutetium-photodynamic therapy of prostate cancer:

Results show PDT to induce large, transient increases in serum PSA levels. Patients who experienced high PDT dose showed greater short-term increase in PSA and a significantly more durable PSA response (biochemical delay). These data strongly promote the need for individualized delivery of PDT dose and assessment of treatment effect in PDT of prostate cancer. Information gained from such patient-specific measurements could facilitate the introduction of multiple PDT sessions in patients who would benefit. [source: Clin Cancer Res. 2008 Aug 1;14(15):4869-76.]

2. Increasing damage to tumor blood vessels during motexafin lutetium-PDT:

Photodynamic therapy (PDT) with low light fluence rate has rarely been studied in protocols that use short drug-light intervals and thus deliver illumination while plasma concentrations of photosensitizer are high, creating a prominent vascular response. In this study, the effects of light fluence rate on PDT response were investigated using motexafin lutetium (10 mg/kg) in combination with 730 nm light and a 180-min drug-light interval. At 180 min, the plasma level of photosensitizer was 5.7 ng/microl compared to 3.1 ng/mg in RIF tumor, and PDT-mediated vascular effects were confirmed by a spasmodic decrease in blood flow during illumination. Light delivery at 25 mW/cm(2) significantly improved long-term tumor responses over that at 75 mW/cm(2). This effect could not be attributed to oxygen conservation at low fluence rate, because 25 mW/cm(2) PDT provided little benefit to tumor hemoglobin oxygen saturation. However, 25 mW/cm(2) PDT did prolong the duration of ischemic insult during illumination and was correspondingly associated with greater decreases in perfusion immediately after PDT, followed by smaller increases in total hemoglobin concentration in the hours after PDT. Increases in blood volume suggest blood pooling from suboptimal vascular damage; thus the smaller increases after 25 mW/cm(2) PDT provide evidence of more widespread vascular damage, which was accompanied by greater decreases in clonogenic survival. Further study of low fluence rate as a means to improve responses to PDT under conditions designed to predominantly damage vasculature is warranted. [source: Radiat Res. 2010 Sep;174(3):331-40.].

  1: Busch TM, Wang HW, Wileyto EP, Yu G, Bunte RM. Increasing damage to tumor blood vessels during motexafin lutetium-PDT through use of low fluence rate. Radiat Res. 2010 Sep;174(3):331-40. PubMed PMID: 20726728; PubMed Central PMCID: PMC2995951.

2: Patel H, Mick R, Finlay J, Zhu TC, Rickter E, Cengel KA, Malkowicz SB, Hahn SM, Busch TM. Motexafin lutetium-photodynamic therapy of prostate cancer: short- and long-term effects on prostate-specific antigen. Clin Cancer Res. 2008 Aug 1;14(15):4869-76. PubMed PMID: 18676760; PubMed Central PMCID: PMC2680073.

3: Wang HW, Finlay JC, Lee K, Zhu TC, Putt ME, Glatstein E, Koch CJ, Evans SM, Hahn SM, Busch TM, Yodh AG. Quantitative comparison of tissue oxygen and motexafin lutetium uptake by ex vivo and noninvasive in vivo techniques in patients with intraperitoneal carcinomatosis. J Biomed Opt. 2007 May-Jun;12(3):034023. PubMed PMID: 17614731.

4: Finlay JC, Zhu TC, Dimofte A, Stripp D, Malkowicz SB, Busch TM, Hahn SM. Interstitial fluorescence spectroscopy in the human prostate during motexafin lutetium-mediated photodynamic therapy. Photochem Photobiol. 2006 Sep-Oct;82(5):1270-8. PubMed PMID: 16808592.

5: Du KL, Mick R, Busch TM, Zhu TC, Finlay JC, Yu G, Yodh AG, Malkowicz SB, Smith D, Whittington R, Stripp D, Hahn SM. Preliminary results of interstitial motexafin lutetium-mediated PDT for prostate cancer. Lasers Surg Med. 2006 Jun;38(5):427-34. PubMed PMID: 16788929.

6: Ross HM, Smelstoys JA, Davis GJ, Kapatkin AS, Del Piero F, Reineke E, Wang H, Zhu TC, Busch TM, Yodh AG, Hahn SM. Photodynamic therapy with motexafin lutetium for rectal cancer: a preclinical model in the dog. J Surg Res. 2006 Oct;135(2):323-30. Epub 2006 May 2. PubMed PMID: 16650871.

7: Verigos K, Stripp DC, Mick R, Zhu TC, Whittington R, Smith D, Dimofte A, Finlay J, Busch TM, Tochner ZA, Malkowicz S, Glatstein E, Hahn SM. Updated results of a phase I trial of motexafin lutetium-mediated interstitial photodynamic therapy in patients with locally recurrent prostate cancer. J Environ Pathol Toxicol Oncol. 2006;25(1-2):373-87. PubMed PMID: 16566729.

8: Yeung PF. Motexafin lutetium (Pharmacyclics). IDrugs. 2001 Mar;4(3):351-9. PubMed PMID: 16025394.

9: Zhu TC, Finlay JC, Hahn SM. Determination of the distribution of light, optical properties, drug concentration, and tissue oxygenation in-vivo in human prostate during motexafin lutetium-mediated photodynamic therapy. J Photochem Photobiol B. 2005 Jun 1;79(3):231-41. Epub 2004 Dec 2. PubMed PMID: 15896650.

10: Miles D, Mody TD, Hatcher LI, Fiene J, Stiles M, Lin PP, Lee JW. Quantitation of motexafin lutetium in human plasma by liquid chromatography-tandem mass spectrometry and inductively coupled plasma-atomic emission spectroscopy. AAPS PharmSci. 2003;5(3):E23. PubMed PMID: 14621958; PubMed Central PMCID: PMC2750933.

11: Kereiakes DJ, Szyniszewski AM, Wahr D, Herrmann HC, Simon DI, Rogers C, Kramer P, Shear W, Yeung AC, Shunk KA, Chou TM, Popma J, Fitzgerald P, Carroll TE, Forer D, Adelman DC. Phase I drug and light dose-escalation trial of motexafin lutetium and far red light activation (phototherapy) in subjects with coronary artery disease undergoing percutaneous coronary intervention and stent deployment: procedural and long-term results. Circulation. 2003 Sep 16;108(11):1310-5. Epub 2003 Aug 25. PubMed PMID: 12939212.

12: Zhu TC, Hahn SM, Kapatkin AS, Dimofte A, Rodriguez CE, Vulcan TG, Glatstein E, Hsi RA. In vivo optical properties of normal canine prostate at 732 nm using motexafin lutetium-mediated photodynamic therapy. Photochem Photobiol. 2003 Jan;77(1):81-8. PubMed PMID: 12856887.

13: Dimofte A, Zhu TC, Hahn SM, Lustig RA. In vivo light dosimetry for motexafin lutetium-mediated PDT of recurrent breast cancer. Lasers Surg Med. 2002;31(5):305-12. PubMed PMID: 12430147.

14: Chou TM, Woodburn KW, Cheong WF, Lacy SA, Sudhir K, Adelman DC, Wahr D. Photodynamic therapy: applications in atherosclerotic vascular disease with motexafin lutetium. Catheter Cardiovasc Interv. 2002 Nov;57(3):387-94. Review. PubMed PMID: 12410519.

15: Solonenko M, Cheung R, Busch TM, Kachur A, Griffin GM, Vulcan T, Zhu TC, Wang HW, Hahn SM, Yodh AG. In vivo reflectance measurement of optical properties, blood oxygenation and motexafin lutetium uptake in canine large bowels, kidneys and prostates. Phys Med Biol. 2002 Mar 21;47(6):857-73. PubMed PMID: 11936174.

16: Yamaguchi A, Woodburn KW, Hayase M, Hoyt G, Robbins RC. Photodynamic therapy with motexafin lutetium (Lu-Tex) reduces experimental graft coronary artery disease. Transplantation. 2001 Jun 15;71(11):1526-32. PubMed PMID: 11435960.

17: Chen Z, Woodburn KW, Shi C, Adelman DC, Rogers C, Simon DI. Photodynamic therapy with motexafin lutetium induces redox-sensitive apoptosis of vascular cells. Arterioscler Thromb Vasc Biol. 2001 May;21(5):759-64. PubMed PMID: 11348871.

18: Hsi RA, Kapatkin A, Strandberg J, Zhu T, Vulcan T, Solonenko M, Rodriguez C, Chang J, Saunders M, Mason N, Hahn S. Photodynamic therapy in the canine prostate using motexafin lutetium. Clin Cancer Res. 2001 Mar;7(3):651-60. PubMed PMID: 11297261.

19: Griffin GM, Zhu T, Solonenko M, Del Piero F, Kapakin A, Busch TM, Yodh A, Polin G, Bauer T, Fraker D, Hahn SM. Preclinical evaluation of motexafin lutetium-mediated intraperitoneal photodynamic therapy in a canine model. Clin Cancer Res. 2001 Feb;7(2):374-81. PubMed PMID: 11234893.

20: Hayase M, Woodbum KW, Perlroth J, Miller RA, Baumgardner W, Yock PG, Yeung A. Photoangioplasty with local motexafin lutetium delivery reduces macrophages in a rabbit post-balloon injury model. Cardiovasc Res. 2001 Feb 1;49(2):449-55. PubMed PMID: 11164855.

21: Parise RA, Miles DR, Egorin MJ. Sensitive high-performance liquid chromatographic assay for motexafin gadolinium and motexafin lutetium in human plasma. J Chromatogr B Biomed Sci Appl. 2000 Dec 1;749(2):145-52. PubMed PMID: 11145051.

22: Yamaguchi A, Woodburn KW, Hayase M, Robbins RC. Reduction of vein graft disease using photodynamic therapy with motexafin lutetium in a rodent isograft model. Circulation. 2000 Nov 7;102(19 Suppl 3):III275-80. PubMed PMID: 11082401.

23: Rockson SG, Kramer P, Razavi M, Szuba A, Filardo S, Fitzgerald P, Cooke JP, Yousuf S, DeVault AR, Renschler MF, Adelman DC. Photoangioplasty for human peripheral atherosclerosis: results of a phase I trial of photodynamic therapy with motexafin lutetium (Antrin). Circulation. 2000 Nov 7;102(19):2322-4. PubMed PMID: 11067782.