The Structures of Gd(III) Chelates Conjugated at the Periphery of 3-(1’-Hexyloxy)ethyl-3-devinylpyropheophorbide-a (HPPH) Have a Significant Impact on the Imaging and Therapy of Cancer

3-(1’-Hexyloxyethyl)-3-devinyl-pyropheophorbide-a (HPPH or Photochlor), a tumor-avid chlorophyll-a derivative currently undergoing human clinical trials, was conjugated at various peripheral positions (position-17 or 20) of HPPH with either Gd(III)-aminobenzyl-DTPA (Gd(III) DTPA) or Gd(III)-aminoethylamido-DOTA (Gd(III) DOTA). The corresponding conjugates were evaluated for in vitro PDT efficacy, T₁, T₂ relaxivities, in vivo fluorescence, and MR imaging under similar treatment parameters. Among these analogs, the water-soluble Gd(III)-aminoethylamido-DOTA linked at position-17 of HPPH, i. e., HPPH-17-Gd(III) DOTA, demonstrated strong potential for tumor imaging by both MR and fluorescence, while maintaining the PDT efficacy in BALB/c mice bearing Colon-26 tumors (7/10 mice were tumor free on day 60). In contrast to Gd(III) DTPA (Magnevist) and Gd(III) DOTA (Dotarem), the HPPH-Gd(III) DOTA retains in the tumor for a long period of time (24 to 48 h) and provides an option of fluorescence-guided cancer therapy. Thus, a single agent can be used for cancer-imaging and therapy. However, further detailed pharmacokinetic, pharmacodynamic, and toxicological studies of the conjugate are required before initiating Phase I human clinical trials.     

Sintered silicon nitride/nano-silicon carbide materials based on preceramic polymers and ceramic powder

A flexible method is presented, which enables the fabrication of porous as well as dense Si₃N₄/nano-SiC components by using Si₃N₄ powder and a preceramic polymer (polycarbosilazane) as alternative ceramic forming binder. The SiCN polymer benefits consolidation as well as shaping of the green body and partially fills the interstices between the Si₃N₄ particles. Cross-linking of the precursor at 300 °C increases the mechanical stability of the green bodies and facilitates near net shape machining. At first, pyrolysis leads to porous ceramic bodies. Finally, subsequent gas pressure sintering results in dense Si₃N₄/nano-SiC ceramics. Due to the high ceramic yield of the polycarbosilazane binder, the shrinkage during sintering is significantly reduced from 20 to 15 lin.%. Investigations of the sintered ceramics reveal, that the microstructure of the Si₃N₄ ceramic contains approx. 6 vol.% nano-scaled SiC segregations, which are located both at the grain boundaries and as inclusions in the Si₃N₄ grains.