Lutetium texaphyrin, PCI-0123, is a pure, water-soluble photosensitizer with a large broad absorption band centered at 732 nm. The compound was tested for photodynamic therapy (PDT) effectiveness in a murine mammary cancer model. The texaphyrin macrocycle as illustrated by magnetic resonance imaging and 14C-radiolabeled texaphyrin studies was shown to be tumor selective; a tumor-to-muscle ratio of 10.55 was seen after 5 h. Lutetium texaphyrin, at a drug dose of 20 mumol/kg with irradiation 5 h postinjection at 150 J/cm2 and 150 mW/cm2, had significant efficacy (P < 0.0001) in treating neoplasms of moderate size (40 +/- 14 mm3) and also had significant efficacy (P < 0.0001) in treating larger neoplasms (147 +/- 68 mm3). The PDT efficacy was correlated with the time interval between PCI-0123 administration and light exposure. A 100% cure rate was achieved when photoirradiation took place 3 h postinjection compared to 50% for 5 h using 10 mumol/kg and 150 J/cm2 at 150 mW/cm2. The PDT efficacy was attributable to the selective uptake/retention of the texaphyrin photosensitizer in addition to the depth of light penetration achievable at the 732 nm laser irradiation.

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Hematide is an investigational pegylated synthetic peptide that stimulates erythropoiesis in animal models and is being developed for the treatment of anemia associated with chronic renal failure and cancer. This study evaluated the safety and pharmacodynamics of single, intravenous doses (0.025, 0.05, and 0.1 mg/kg) of Hematide in 28 healthy male volunteers. All doses of Hematide were well tolerated, with safety profiles similar to those of placebo. Hematide showed a dose-dependent increase in reticulocytes. The 0.1-mg/kg dose was associated with a statistically significant increase in hemoglobin (Hgb) from baseline compared to the placebo group (13.6 ؎ 3.9 g/L [1. 36 IntroductionThere are several common clinical situations in which anemia is the result of hypoproliferation of red blood cell (RBC) precursors secondary to erythropoietin (EPO) deficiency. These include anemias associated with chronic kidney disease (CKD), chronic inflammation, and cancer, with or without myelosuppressive therapy. In these situations, recombinant human EPO (rHuEPO) has been used successfully to increase hemoglobin (Hgb) levels, reduce fatigue, and improve daily function.Hematide is a synthetic, dimeric peptidic erythropoiesisstimulating agent (ESA) covalently linked to polyethylene glycol (PEG) and is being developed for the treatment of anemia associated with chronic renal failure and cancer. Because its primary amino acid sequence is unrelated to that of rHuEPO, Hematide is unlikely to induce a cross-reactive immune response against endogenous EPO. 1 This potentially reduces the risk of pure red cell aplasia (PRCA), a rare complication caused by an immune response to rHuEPO. PRCA reached a peak incidence outside of the United States in 2001 to 2002, largely related to a change in formulation of the product. 2,3 Hematide binds to and activates the human EPO receptor, stimulating the proliferation and differentiation of human red cell precursors in vitro in a manner similar to ESAs. 1 A predictable, dose-related effect on reticulocyte and Hgb levels has been observed in rats and monkeys. 1 The design of this first study of Hematide in humans was based on these nonclinical data and the published reports of ESAs in approximately 400 healthy volunteers. [4][5][6][7][8][9][10][11][12][13] This study was designed to evaluate the safety and pharmacokinetic and pharmacodynamic profiles of single intravenous dose levels of the drug and to determine the minimum pharmacologic active dose (PAD) in healthy subjects. Results of the pharmacokinetic analysis will be published separately. Subjects, materials, and methods EligibilityEligible subjects were men, 18 to 40 years of age, with a body mass index (BMI) of 18 to 30 kg/m 2 , without any clinically significant medical condition. At study entry, subjects were to have a Hgb value of 160 g/L (16 g/dL) or less, and normal values for ferritin, white blood cell count, and platelet count. All subjects were informed of the investigational nature of this study and signed informed consent. The stud...