Synthesis, proteolytic stability, and in vitro evaluation of DOTA conjugated p160 peptide based radioconjugates: [Lu-177]Lu-DOTA-p160

In this work, we describe the synthesis, in vitro stability, and preliminary biological evaluation of [Lu-177]Lu-DOTA-p160 peptide-based radiopharmaceuticals. Our findings highlight that all DOTA-p160-peptide radioconjugates exhibit favorable proteolytic and enzymatic stability with a prolonged half-life in human plasma and serum. Cell uptake studies carried out on MCF-7 cell line revealed saturable binding of the radioconjugates in the nanomolar range, thereby demonstrating their promising potential in the imaging and therapy of breast tumors

Exhalation of I-131 after radioiodine therapy: measurements in exhaled air

Purpose A considerable amount of radioiodine is exhaled after radioiodine therapy leading to unwanted radiation exposure through inhalation. This study focused on the concentration of radioactivity exhaled and its chemical nature. Methods Air exhaled by 47 patients receiving I-131-iodine for different thyroid diseases (toxic goitre n=26, Graves' disease n=13, thyroid cancer n=8) was investigated with a portable constant air-flow sampler. Different chemical iodine species were collected separately (organic, elemental and aerosolic) up to 26 h after administration of the radioiodine capsule. The data approximated to a monoexponential time-activity curve when integrated over 100 h. The radioactivity in the filters was measured with a well counter at defined time points after administration. Results The radioactivity of I-131 in the exhaled air 1 h after administration ranged from 1 to 100 kBq/m(3). Two parameters (half-life of radioiodine exhalation and time-integrated activity over 100 h) were substantially higher in patients with cancer after near-total thyroidectomy (11.8 +/- 2.1 h and 535 +/- 140 kBq / m(3), respectively) than in patients with hyperfunctioning thyroid tissue due to toxic adenoma (7.6 +/- 2.5 h and 115 +/- 27 kBq / m(3), respectively) or Graves' disease (6.4 +/- 3.6 h and 113 +/- 38 kBq / m(3), respectively). The percentage of radioiodine in the exhaled air in relation to radioiodine administered to the patient was between 80 ppm and 150 ppm. The fraction of organically bound radioiodine (mean value) for all time points after administration was 94-99.9%. This percentage did not depend on the type of thyroid disease. Conclusion The amount of exhaled radioiodine is small but by no means negligible on the first day after administration. This is the first study to provide experimental evidence on a systematic basis that radioiodine becomes exhalable in vivo, i.e. in the patient. The mechanism of organification of orally administered radioiodine remains to be investigated

Characterization of a Cell-Penetrating Peptide with Potential Anticancer Activity

Cell-penetrating peptides (CPPs) are still an interesting and viable alternative for drug delivery applications. CPPs contain considerably high amounts of positively charged amino acids, imparting them with cationic character. Tumor cells are characterized by an enhanced anionic nature of their membrane surface, a property that could be used by CPPs to target these cells. We recently identified a branched CPP that displays a high internalization capacity while exhibiting selectivity for certain tumor cell types. In this study we elucidated this observation in greater detail by investigating the underlying mechanism behind the cellular uptake of this peptide. An additional cytotoxicity screen against several cancer cell lines indeed demonstrates high cytotoxic activity against cancer cells over normal fibroblasts. Furthermore, we show that this feature can be used for delivering the anticancer drug actinomycinD with high efficiency in the MCF-7 cancer cell line

Dual-Tracer PET/CT Protocol with [F-18]-FDG and [Ga-68]Ga-FAPI-46 for Cancer Imaging: A Proof of Concept

Imaging studieswithPET tracers acting as fibroblast activation protein inhibitors (FAPIs) show promising results that could usefully complement [F-18]-FDG in cancer imaging. Methods: All patients received [F-18]-FDG PET/CT and dual-tracer PET/CT after an additional injection of [Ga-68]Ga-FAPI-46 after the [F-18]-FDG PET/CT. Two readers visually compared detection rate and analyzed target-to-background ratios for tumor and metastatic tissue in single- and dual-tracer PET/CT. Results: Detection rate in dual-tracer PET/CT was visually as good as that in single-tracer PET/CT in 4 patients and superior in 2 patients, whereas target-to-background ratios were significantly higher in dualtracer PET/CT. Conclusion: Dual-tracer [F-18]-FDG/[Ga-68]Ga-FAPI-46 PET/CT within a single session is feasible and has potential. The dualtracer approach may have superior sensitivity to [F-18]-FDG PET/CT alone without compromising individual assessment of either scan

Click functionalized biocompatible gadolinium oxide core-shell nanocarriers for imaging of breast cancer cells

Site-specific delivery using functionalized nanocarriers is in high demand in imaging applications of modern clinical research. To improve the imaging capabilities of conventionally used contrast agents and expand the targeting accuracy, functional gadolinium oxide based nanocarriers originated from homogeneous core shells structures (Gd2O3@SiO2@Fe3O4) were developed using a multilayer formation approach. The synthesis and chemical configuration for the covalent binding of macrocyclic chelating agents and estrogen targeting molecules on these nanocarriers were designed by a two-step chemical synthesis method. Initially, SiO2@Fe3O4 structures were prepared and encapsulated with a homogenous thin Gd2O3 overlayer. The exterior surface of the as-prepared carriers offered chemical binding with a breast cancer specific estrogen molecule, covalently grafted through a Click-Chemistry protocol. In the next step, to enhance the diagnostic imaging capabilities of these carriers, thiocyanate-linked chelator molecule, DOTA, was attached to the surface of estrogen bound Gd2O3@SiO2@Fe3O4 using basic reaction conditions. The active amino groups before and after conjugation of estrogen molecules on the surface were quantified using a fluorescamine based approach. Due to the covalent binding of the macrocyclic chelator to the Gd2O3@SiO2@Fe3O4 surface, core shell carriers showed potential radiolabeling efficiency using positron emitter radionuclide, gallium-68 (Ga-68). Intracellular uptake of estrogen-conjugated carriers was evaluated with MCF7 breast cancer cell lines using confocal laser scanning microscopy and fluorescent flow cytometry. In addition, in vitro cytotoxicity studies of functional nanocarriers as compared to bare nanoparticles showed reduced toxicity to HEK-293 cells demonstrating the role of surface attached molecules in preventing direct exposure of the Gd2O3 surface to the cells. The as-developed gadolinium based nanocarriers presented excellent capabilities as biocompatible target-specific imaging probes which indicates great potential in the field of dual-mode contrast agents