Browsing by Subject "Astatine"

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    ItemOpen Access
    3-[211At]astato-4-fluorobenzylguanidine: a potential therapeutic agent with prolonged retention by neuroblastoma cells.
    (Br J Cancer, 1997) Vaidyanathan, G; Zhao, XG; Larsen, RH; Zalutsky, MR
    An analogue of meta-iodobenzylguanidine (MIBG) in which an aromatic hydrogen was replaced with fluorine has been found to possess many properties similar to those of the parent compound. Moreover, 4-fluoro-3-iodobenzylguanidine (FIBG) was retained in vitro by human neuroblastoma cells to a much greater extent than MIBG itself. Since alpha-emitters such as 211At could be valuable for the treatment of micrometastatic disease, an FIBG analogue in which the iodine atom is replaced by 211At would be of interest. In this study, we have evaluated the in vitro and in vivo properties of 3-[211At]astato-4-fluorobenzylguanidine ([211At]AFBG). The specific binding of [211At]AFBG to SK-N-SH human neuroblastoma cells remained fairly constant over 2- to 3-log activity range and was similar to that of [131I]MIBG. The uptake of [211At]AFBG by this cell line was reduced by desipramine, ouabain, 4 degrees C incubation, noradrenaline, unlabelled MIBG and FIBG, suggesting that its uptake is specifically mediated through an active uptake-1 mechanism. Over the 16 h period studied, the amount of [211At]AFBG retained was similar to that of [131I]FIBG, whereas the per cent of retained meta-[211At]astatobenzylguanidine ([211At]MABG) was considerably less than that of [131I]FIBG (53% vs 75%; P < 0.05). The IC50 values for the inhibition of uptake of [131I]MIBG, [211At]MABG, [125I]FIBG and [211At]AFBG by unlabelled MIBG were 209, 300, 407 and 661 nM respectively, suggesting that the affinities of these tracers for the noradrenaline transporter in SK-N-SH cells increase in that order. Compared with [211At]MABG, higher uptake of [211At]AFBG was seen in vivo in normal mouse target tissues such as heart and, to a certain extent, in adrenals. That the uptake of [211At]AFBG in these tissues was related to the uptake-1 mechanism was demonstrated by its reduction when mice were pretreated with desipramine. However, the stability of [211At]AFBG towards in vivo dehalogenation was less than that of [211At]MABG, as evidenced by the higher uptake of 211At in thyroid, spleen, lungs and stomach.
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    ItemEmbargo
    Assessing Astatine-211 SPECT Image Quality in Relevant Organs
    (2024) Wong, Ye Wan Evan

    Theranostics is an evolving approach in nuclear medicine that aims to combine diagnostic and therapeutic value into a single agent of delivery. With increased interest in alpha-emitting radionuclides for their short effective range and high linear energy transfer, astatine-211 is a promising radionuclide for therapy applications. Previously at Duke University, the ability to image and quantitate images of astatine-211 was investigated and determined to be a challenge due to attenuation and collimation effects on desired photons for imaging, and undesirable high energy emission contributions. This research builds on that previous work to investigate the image quality extent of single photon planar and SPECT imaging for astatine-211 when considering relevant organs that could be at risk for radiation damage based on the distribution of the molecule carrying the At-211. The investigation is broken down into several experiments that provide the basis for understanding the potential of astatine-211 to perform as an imaging radionuclide, and the needed factors for image reconstruction including the appropriate linear attenuation coefficient and k-factor for dual-energy scatter correction. Two phantom designs were created. One was used to provide a baseline image quality comparison of four radionuclides (F-18 for PET, Tc-99m, Lu-177, and At-211 for single photon planar imaging). The other represented the salivary glands in the head and kidneys and tumors in the torso. Imaging the same realistically large phantom showed that only the fluorine-18 PET images 1 cm targets successfully, while technetium-99m and lutetium-177 are comparable in imaging 2 cm and 3 cm targets, and astatine-211 can only image 3 cm targets. This work successfully simulated the salivary glands and kidneys in an anthropomorphic phantom. The results indicated that the use of a k-factor of 1.1 is reasonable in the scatter correction of imaging astatine-211, which effectively reduced downscattered gamma rays in the images. Additionally, the results confirm that the medium energy general purpose collimator is better suited than the low energy high resolution collimator for imaging astatine-211 with improved SNR and comparable noise quality.

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    ItemOpen Access
    Cytotoxicity of alpha-particle-emitting astatine-211-labelled antibody in tumour spheroids: no effect of hyperthermia.
    (Br J Cancer, 1998-03) Hauck, ML; Larsen, RH; Welsh, PC; Zalutsky, MR
    The high linear energy transfer, alpha-particle-emitting radionuclide astatine-211 (211At) is of interest for certain therapeutic applications; however, because of the 55- to 70-microm path length of its alpha-particles, achieving homogeneous tracer distribution is critical. Hyperthermia may enhance the therapeutic efficacy of alpha-particle endoradiotherapy if it can improve tracer distribution. In this study, we have investigated whether hyperthermia increased the cytotoxicity of an 211At-labelled monoclonal antibody (MAb) in tumour spheroids with a radius (approximately 100 microm) greater than the range of 211At alpha-particles. Hyperthermia for 1 h at 42 degrees C was used because this treatment itself resulted in no regrowth delay. Radiolabelled chimeric MAb 81C6 reactive with the extracellular matrix antigen tenascin was added to spheroids grown from the D-247 MG human glioma cell line at activity concentrations ranging from 0.125 to 250 kBq ml(-1). A significant regrowth delay was observed at 125 and 250 kBq ml(-1) in both hyperthermia-treated and untreated spheroids. For groups receiving hyperthermia, no increase in cytotoxicity was seen compared with normothermic controls at any activity concentration. These results and those from autoradiographs indicate that hyperthermia at 42 degrees C for 1 h had no significant effect on the uptake or distribution of this antitenascin MAb in D-247 MG spheroids.
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    ItemOpen Access
    Toxicity to neuroblastoma cells and spheroids of benzylguanidine conjugated to radionuclides with short-range emissions.
    (Br J Cancer, 1998-06) Cunningham, SH; Mairs, RJ; Wheldon, TE; Welsh, PC; Vaidyanathan, G; Zalutsky, MR
    Radiolabelled meta-iodobenzylguanidine (MIBG) is selectively taken up by tumours of neuroendocrine origin, where its cellular localization is believed to be cytoplasmic. The radiopharmaceutical [131I]MIBG is now widely used in the treatment of neuroblastoma, but other radioconjugates of benzylguanidine have been little studied. We have investigated the cytotoxic efficacy of beta, alpha and Auger electron-emitting radioconjugates in treating neuroblastoma cells grown in monolayer or spheroid culture. Using a no-carrier-added synthesis route, we produced 123I-, 125I-, 131I- and 211At-labelled benzylguanidines and compared their in vitro toxicity to the neuroblastoma cell line SK-N-BE(2c) grown in monolayer and spheroid culture. The Auger electron-emitting conjugates ([123I]MIBG and [125I]MIBG) and the alpha-emitting conjugate ([211At]MABG) were highly toxic to monolayers and small spheroids, whereas the beta-emitting conjugate [131I]MIBG was relatively ineffective. The Auger emitters were more effective than expected if the cellular localization of MIBG is cytoplasmic. As dosimetrically predicted however, [211At]MABG was found to be extremely potent in terms of both concentration of radioactivity and number of atoms ml(-1) administered. In contrast, the Auger electron emitters were ineffective in the treatment of larger spheroids, while the beta emitter showed greater efficacy. These findings suggest that short-range emitters would be well suited to the treatment of circulating tumour cells or small clumps, whereas beta emitters would be superior in the treatment of subclinical metastases or macroscopic tumours. These experimental results provide support for a clinical strategy of combinations ('cocktails') of radioconjugates in targeted radiotherapy.