99mTc‐anti‐epidermal growth factor receptor nanobody for tumor imaging

Nanobodies are important biomolecules for tumor targeting. In this study, we synthesized and labeled anti‐epidermal growth factor receptor (EGFR) nanobody OA‐cb6 with ^99mTc(CO)₃⁺ and evaluated its characteristics for targeting the EGFR in the A431 human epidermal carcinoma cell line. Nanobody radiolabeling was achieved with high yield and radiochemical purity, and the radioconjugate was stable. Biodistribution results in nude mice exhibited a favorable tumor‐to‐muscle ratio at 4‐hr postinjection, and tumor location was visualized at 4 hr after injection of radiolabeled nanobody. Our result showed that the OA‐cb6‐^99mTc‐tricarbonyl radiolabeled nanobody is a promising radiolabeled biomolecule for tumor imaging in cancers with high EGFR overexpression.     

Melissa Officinalis L. aqueous extract pretreatment decreases methotrexate-induced hepatotoxicity at lower dose and increases 99mTc-phytate liver uptake,as a probe of liver toxicity assessment,in rats

Annals of Nuclear Medicine - Hepatotoxicity remains amongst the restricting factors of Methotrexate (MTX)-associated cancer therapy, especially in high doses of chemo-drugs or prolonged treatment....     

Significance of Platelet Count in Esophageal Carcinomas

Background/Aim:

Thrombocytosis is found to be associated with unfavorable prognosis in esophageal carcinoma. Platelets produce thymidine phosphorylase which is a platelet-derived endothelial cell growth factor with angiogenic activity. Increased platelet count may be translated into enhanced tumor growth. We examined the relation between platelet count and several prognostic variables in patients with esophageal cancer.

Patients and Methods:

Three hundred and eighty-one cases with esophageal cancer that underwent esophagectomy in a referral cancer institute during a 5-year period were studied retrospectively. The relation between preoperative platelet count and patient age, gender, site of tumor, presence of multiple cancers and clinicopathological characteristics including histological type, tumor size, depth of penetration (T), lymph node involvement (N), distant metastasis (M), degree of differentiation, presence of vascular, lymphatic and perineural invasion was examined.

Results:

Squamous cell carcinoma (SCC) constituted 93% and adenocarcinoma 7% of cases. Most of patients were in stage III, followed by stage II. The mean platelet count was 245±76 (× 10⁹ /L). There was no statistically significant correlation between platelet counts with prognostic factors except a weak linear correlation between platelet count and and tumor size (P= 0.03, Pearson correlation coefficient: 0.16). Patients with adenocarcinoma had a higher platelet count than those with SCC (P= 0.003).

Conclusion:

Platelet count does not correlate with prognostic factors in esophageal cancer. However, it is significantly different between SCC and adenocarcinoma of esophagus.     

A HER2-targeted RNA aptamer molecule labeled with 99mTc for single-photon imaging in malignant tumors

A modified RNA aptamer with HER2-specific binding was conjugated to hynic and labeled with ^99mTc, for potential use as a radiopharmaceutical for diagnostic imaging of ovarian cancer cells (SKOV-3) with high HER2 expression. The aptamer was radiolabeled with ^99mTc by using hynic as the chelator and tricine as the co-ligand. Stability testing of the radioconjugated aptamer was performed via ITLC and SDS-PAGE in normal saline and serum. The aptamer-radionuclide conjugate was evaluated for cellular HER2-specific binding, saturation affinity, and cellular internalization in SKOV-3 and MCF-7 cells, and its biodistribution properties were assessed in normal and SKOV-3 tumor-bearing mice. Radiolabeling of the aptamer was achieved with high yield and radiochemical purity, and the ^99mTc-hynic-RNA aptamer was highly stable in normal saline and serum. Cellular experiments showed specific binding of the aptamer to the HER2 receptor with a dissociation constant of 27 nM. Rapid blood clearance was observed after injection of the ^99mTc-hynic-RNA aptamer, and the main excretion route was via the hepatobilary system. While the radioconjugated aptamer bound specifically to the HER2 receptor on cells in vitro, it did not show any significant tumor-to-blood or tumor-to-muscle ratios in mice. Modifications to radiolabeled aptamer will require improving its pharmacokinetic properties and tumor uptake in vivo.     

Tumor targeting with a 99mTc-labeled AS1411 aptamer in prostate tumor cells

AS1411, a 26-base guanine-rich oligonucleotide aptamer, has high affinity to nucleolin, mainly on tumor cell surfaces. In this study, a modified AS1411 was labeled with ^99mTc and evaluated as a potential tumor-targeting agent for imaging. The AS1411 aptamer was conjugated with HYNIC and labeled with ^99mTc in the presence a co-ligand. Radiochemical purity and stability testing of the ^99mTc–HYNIC–AS1411 aptamer were carried out with thin layer chromatography and a size-exclusion column in normal saline and human serum. Cellular nucleolin-specific binding, cellular internalization in DU-145 cells, as high levels of nucleolin expression, were performed. Additionally, biodistribution in normal mice and DU-145 tumour-bearing mice was assessed. Radiolabeling of the aptamer resulted in a reasonable yield and radiochemical purity after purification. The aptamer was stable in normal saline and human serum, and cellular experiments demonstrated specific binding of the AS1411 aptamer to the nucleolin protein. Based on biodistribution assessment of ^99mTc–HYNIC–AS1411, rapid blood clearance was seen after injection and it appears that the excretion route was via the urinary system at 1?h post-injection. Tumours also showed a higher accumulation of radioactivity with this labeled aptamer. ^99mTc–AS1411 can be a potential tool for the molecular imaging of nucleolin-overexpressing cancers.