Multifunctional nanoparticle PEG­Ce6­Gd for MRI­guided photodynamic therapy.

Gliomas are one of the most common types of primary brain tumors. Despite recent advances in the combination of surgery, radiotherapy, systemic therapy (chemotherapy, targeted therapy) and supportive therapy in the multimodal treatment of gliomas, the overall prognosis remains poor and the long­term survival rate is low. Thus, it is crucial to develop a novel glioma management method. Due to its relatively non­invasive, selective and repeatable characteristics, photodynamic therapy (PDT) has been investigated for glioma therapy in the past decade, exhibiting higher selectivity and lower side effects compared with those of conventional therapy. However, most of the photosensitizers (PSs) are highly hydrophobic, leading to poor water solubility, rapid degradation with clearance in blood circulation and ultimately, low bioavailability. In the present study, hydrophilic polyethylene glycol (PEG)­chlorin e6 (Ce6) chelated gadolinium ion (Gd3+) nanoparticles (PEG­Ce6­Gd NPs) were synthesized via a chelation and self­assembly process. Initially, the cell cytotoxicity of PEG­Ce6­Gd NPs was evaluated with or without laser irradiation. The in vitro study demonstrated the lack of toxicity of PEG­Ce6­Gd NPs to tumor cells in the absence of laser irradiation. However, its toxicity was enhanced under laser irradiation. Moreover, the size and weight of brain tumors were significantly decreased in mice with glioma xenografts, which was further confirmed via histological analysis. Subsequently, the results indicated that the PEG­Ce6­Gd NPs had a favorable T1­weighted contrast performance (0.43 mg ml­1 s­1) and were observed to have significant contrast enhancement at the tumor site from 0.25 to 1 h post­injection in vivo. The favorable MRI, as well as the synergetic photodynamic antitumor effect and antineoplastic ability of PEG­Ce6­Gd NPs was identified. It was suggested that PEG­Ce6­Gd NPs had great potential in the diagnosis and PDT treatment of gliomas, and possibly other cancer types, with prospects of clinical application in the near future.

False Negativity of Tc-99m Labeled Sodium Phytate Bone Marrow Imaging Under the Effect of G-CSF Prescription in Aplastic Anemia: A Case Report.

Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic cytokine which controls the differentiation and growth of hematopoietic cells in the bone marrow. We report a severe aplastic anemia (SAA) patient with false-negative 99mTc sodium phytate bone marrow imaging findings under concurrent G-CSF therapy. The first bone marrow imaging showed a normal bone marrow activity. However, the bone marrow biopsy pathology report revealed a lack of hematopoietic cells. Furthermore, the complete blood count indicated severe pancytopenia resulting in the diagnosis of aplastic anemia (AA). A second marrow scan implemented after the stoppage of G-CSF showed an abnormal bone marrow activity, which matched the pathology reports. Accordingly, the concurrent administration of G-CSF was considered as the cause of false-negative bone marrow imaging findings obtained in the first scan. Consequently, it should be kept in mind that a 99mTc sodium phytate bone marrow scintigraphy during the concurrent administration of G-CSF may lead to the achievement of false negative results because it induces changes in bone marrow mimicking a normal marrow scan in patients with AA.

Evaluation of methotrexate-conjugated gadolinium(III) for cancer diagnosis and treatment.

BACKGROUND: Gliomas are one of the most common types of primary brain tumors. It is usually evaluated by gadolinium(III)-based contrast agents by magnetic resonance imaging (MRI) in the clinic. Methotrexate (MTX), as a type of folate analog that inhibits the enzyme dihydrofolate reductase, is widely used as a chemotherapeutic agent to treat gliomas in the experiment. PURPOSE: In this study, a novel theranostic agent MTX-DOTA-Gd (MTX-Gd) was synthesized, which integrates magnetic resonance imaging (MRI) with anticancer treatment. METHODS: MTX-Gd was synthesized by connecting MTX and Gd through 1,4,7,10-tetraazacy-clododecane-1,4,7,10-tetraacetic acid (DOTA). The characterization of MTX-Gd was detected by ultraviolet (UV) and infrared spectroscopy (IR). To confirm the antitumor effect of MTX-Gd, the cytotoxicity of MTX-Gd was examined by the MTT assay. The contrast enhancement of the MTX-Gd was measured through MRI in vitro. Then, nude mice bearing C6 tumor xenografts were used to study in vivo imaging capabilities. RESULTS: The ultraviolet-visible-near infrared radiation (UV-NIR) absorption curve indicated that MTX-Gd had a broad absorption in the region of 500-700 nm. The formation of MTX-Gd was confirmed from the characteristic bands of MTX-DOTA-Gd in the 1413 cm-1 (C-N), 1577 cm-1 (-NH2), and 3429 cm-1 (N-H), in the fourier-transform infrared (FTIR) spectra. MTX-Gd showed little difference in the cell viability compared with MTX, except for the highest concentration (270 µM). In vitro, the imaging of MTX-Gd was significantly brighter than Gd-DOTA at the same concentration, and the brightness and signal intensity of MRI were increased followed by the increased concentration of MTX-Gd. And it also showed that MTX was not visualized on MRI. The other images revealed that the concentration of 4 mM MTX-Gd had the same imaging effect with the concentration of 10 mM Gd-DOTA. Then, MTX-Gd was injected in nude mice bearing C6 tumor xenografts through the tail vein. Significant contrast enhancement was observed at the tumor site from 0.5 h to 3 h. The signal of tumor area was strongest at 3 h due to accumulation by size effect of macromolecules. CONCLUSION: A novel stable and unique theranostic agent (MTX-Gd) was successfully synthe-sized, and it has good stability, strong anticancer ability and excellent magnetic capacity. The methotrexate component of MTX-Gd, as a chemotherapeutic agent, played an important role in targeted therapies of cancer. The DOTA-Gd component of MTX-Gd performed as the MRI contrast agent. The superior MRI imaging performance and synergetic chemical antineoplastic ability of MTX-Gd was revealed, and it has great potential in the diagnosis and treatment of glioma and potentially other cancers, with prospects of clinical application in the near future.

MRI-guided tumor chemo-photodynamic therapy with Gd/Pt bifunctionalized porphyrin.

Porphyrin derivatives have been widely applied in MR imaging and photodynamic cancer therapy. We here report a novel Gd/Pt bifunctionalized porphyrin derivative (Gd/Pt-P1) for MRI-guided chemo-photodynamic cancer therapy. Gd/Pt-P1 was prepared from tetra(4-pyridyl) porphyrin (P1) via step by step coordination to cisplatin and gadolinium (Gd(iii)). Gd/Pt-P1 showed a particularly high synergetic chemo-photodynamic antitumor effect in vivo with a tumor inhibition rate (TIR) of 96.6% and excellent MR imaging performance.