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The high recurrence rate of lung cancer is a major clinical challenge associated with therapy‑resistant cancer stem cells (CSCs), which are rare subpopulations. Future successful treatment is required to also eradicate these subpopulations. Furthermore, the majority of anti‑cancer treatments are being tested in adherent monolayer cultures with the limitations this entails in the translation of results into clinical practice. The present study aimed to establish and characterize patient‑derived long‑term primary lung cancer tumorspheres enriched in CSCs and evaluate the effects of Auger electrons on them. These electrons are emitted from radionuclides that decay by electron capture or internal conversion and have demonstrated promising therapeutic potential. Their low energy (<1 keV) is sufficiently potent to induce DNA double‑strand breaks and eventually cell death while minimizing irradiation of non‑targeted surrounding cells. Labeling a thymidine analog (deoxyuridine) with the Auger electron‑emitting radionuclide [ 125 I], which is exclusively incorporated into the DNA of proliferating cells during the S‑phase, ensures a close distance to the DNA. Primary cell cultures grown as tumorspheres were established and characterized. The tumorspheres were morphologically distinct and differed concerning their proliferation rate and fraction of CSCs. Surface markers associated with CSCs were upregulated and 5‑[ 125 I]iodo‑2'‑deoxyuridine was incorporated in the tumorspheres. The Auger electrons induced DNA double‑strand breaks, G2/M arrest and apoptosis in the tumorspheres; however, the tumorspheres derived from different patients exhibited heterogeneities in their sensitivity to Auger electron irradiation.

Unlabelled: The somatostatin receptor, which is overexpressed by many neuroendocrine tumors, is a well-known target for molecular imaging and peptide receptor radionuclide therapy. Recently, (57)Co-labeled DOTATOC, an octreotide analog, was shown to have the highest affinity yet found for somatostatin receptor subtype 2. The aim of this study was to evaluate the biologic effects of novel cobalt-labeled octreotide analogs targeting the somatostatin receptor to identify promising candidates for molecular imaging and Auger electron-based radionuclide therapy., Methods: Cobalt-labeled DOTATATE, DOTATOC, and DOTANOC were prepared with (57)Co or (58m)Co for SPECT or Auger electron-based therapy, respectively. The cellular uptake and intracellular distribution of the radioligands were characterized with the pancreatic tumor cell line AR42J in vitro, including assessment of the therapeutic effects of (58m)Co-DOTATATE via DNA double-strand break and proliferation assays. Comparisons with the therapeutic effects of (111)In- and (177)Lu-DOTATATE were also performed. Tumor uptake and normal tissue uptake were characterized in a subcutaneous pancreatic tumor mouse model., Results: All 3 cobalt-conjugated peptides resulted in time-dependent and receptor-specific uptake, with a high level (≥88%) of cellular internalization in vitro of the total cell-associated radioactivity. The DNA double-strand break yield showed a dose-dependent increase with activity, whereas cell survival showed a dose-dependent decrease. (58m)Co-DOTATATE was significantly more efficient in cell killing per cumulated decay than (111)In- and (177)Lu-DOTATATE. The in vivo pharmacokinetic studies showed a high level of receptor-specific tumor uptake., Conclusion: All cobalt-labeled radioligands showed a high level of receptor-specific uptake both in vitro and in vivo in tumor-bearing mice. Furthermore, (58m)Co-DOTATATE showed considerable therapeutic effects in vitro and, thus, could be an effective agent for eradicating disseminated tumor cells and micrometastases., (© 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Non-targeted effects, including bystander and systemic effects, play a crucial role during Auger targeted radionuclide therapy. Here, we investigated whether small extracellular vesicles (sEVs) produced by irradiated cells could contribute to the bystander cytotoxic effects in vitro and also to therapeutic efficacy in vivo, after their injection in tumor xenografts. B16F10 melanoma donor cells were exposed to radiolabeled antibodies (Auger radioimmunotherapy, RIT) for 48 h or to X-rays (donor cells). Then, donor cells were incubated with fresh medium for 2 h to prepare conditioned medium (CM) that was transferred onto recipient cells for bystander effect assessment, or used for sEVs enrichment. Resulting sEVs were incubated in vitro with recipient cells for determining bystander cytotoxicity, or injected in B16F10 melanoma tumors harbored by athymic and C57BL/6 mice. In vitro analysis of bystander cytotoxic effects showed that CM killed about 30–40% of melanoma cells. SEVs isolated from CM contributed to this effect. Moreover, the double-stranded DNA (dsDNA) content was increased in sEVs isolated from CM of exposed cells compared to control (not exposed), but the difference was significant only for the X-ray condition. These results were supported by immunodetection of cytosolic dsDNA in donor cells, a phenomenon that should precede dsDNA enrichment in sEVs. However, sEVs cytotoxicity could not be detected in vivo. Indeed, in athymic and in immunocompetent mice that received four intratumoral injections of sEVs (1/day), tumor growth was not delayed compared with untreated controls. Tumor growth was slightly (not significantly) delayed in immunocompetent mice treated with sEVs from X-ray-exposed cells, and significantly with sEVs purified from CM collected after 48 h of incubation. These results highlight the need to determine the optimal conditions, including radiation absorbed dose and sEVs collection time, to obtain the strongest cytotoxic effects. This study demonstrates that sEVs could play a role during Auger RIT through bystander effects in vitro. No systemic effects were observed in vivo, under our experimental conditions. However, X-rays experiments showed that sEVs collection time might be influencing the nature of sEVs, a parameter that should also be investigated during Auger RIT. [ABSTRACT FROM AUTHOR]

Purpose: For the past two decades, high‐Z nanoparticles have been of high interest to improve the therapeutic outcomes of radiation therapy, especially for low‐energy x‐rays. Monte Carlo (MC) simulations have been used to evaluate the boost of dose deposition induced by Auger electrons near the nanoparticle surface, by calculating average energy deposition at the nanoscale. In this study, we propose to go beyond average quantities and quantify the stochastic nature of energy deposition at such a scale. We present results of probability density of the specific energy (restricted to ionization, excitation and electron attachment events) in cylindrical nanotargets of height and radius set at 10 nm. This quantity was evaluated for nanotargets located within 200 nm around 5–50 nm gold nanoparticles (GNPs), for 20–90 keV photon irradiation. Methods: This nanodosimetry study was based on the MC simulation MDM that allows tracking of electrons down to thermalization energy. We introduced a new quantity, namely the probability enhancement ratio (PER), by estimating the probability of imparting to nanotargets a restricted specific energy larger than a threshold z0 (1, 10, and 20 kGy), normalized to the probability for pure water. The PER was calculated as a function of the distance between the nanotarget and the GNP surface. The threshold values were chosen in light of the biophysical model NanOx that predicts cell survival by calculating local lethal events based on the restricted specific energy and an effective local lethal function. z0 then represents a threshold above which the nanotarget damages induce efficiently cell death. Results: Our calculations showed that the PER varied a lot with the GNP radius, the photon energy, z0 and the distance of the GNP to the nanotarget. The highest PER was 95 when the nanotarget was located at 5 nm from the GNP surface, for a photon energy of 20 keV, a threshold of 20 kGy, and a GNP radius of 50 nm. This enhancement dramatically decreased with increasing GNP‐nanotarget distances as it went below 1.5 for distances larger than 200 nm. Conclusions: The PER seems better adapted than the mean dose deposition to describe the formation of biological damages. The significant increase of the PER within 200 nm around the GNP suggests that severe damages could occur for biological nanotargets located near the GNP. These calculations will be used as an input of the biophysical model NanOx to convert PER into estimation of radiation‐induced cell death enhanced by GNPs. [ABSTRACT FROM AUTHOR]

Excess electrons play important roles for the construction of superficial active sites on nanocatalysts. However, providing excess electrons to nanocatalysts in vivo is still a challenge, which limits the applications of nanocatalysts in biomedicine. Herein, auger electrons (AEs) emitted from radionuclide 125 (125I) are used in situ to construct active sites in a nanocatalyst (TiO2) and the application of this method is further extended to cancer catalytic internal radiotherapy (CIRT). The obtained 125I‐TiO2 nanoparticles first construct superficial Ti3+ active sites via the reaction between Ti4+ and AEs. Then Ti3+ stretches and weakens the OH bond of the absorbed H2O, thus enhancing the radiolysis of H2O molecules and generating hydroxyl radicals (•OH). All in vitro and in vivo results demonstrate a good CIRT performance. These findings will broaden the application of radionuclides and introduce new perspectives to nanomedicine. [ABSTRACT FROM AUTHOR]

Graphical abstract AuNCs-HA exhibited PA imaging guided combined radiotherapy, PDT and PTT trimodalites, leading to effectively synergistic anticancer efficacy. Abstract In this work, we developed a novel multifunctional nanoplatform based on hyaluronic acid modified Au nanocages (AuNCs-HA). The rational design of AuNCs-HA renders the nanoplatform three functionalities: (1) AuNCs-HA with excellent LSPR peak in the NIR region act as contrast agent for enhanced photoacoustic (PA) imaging and photothermal therapy (PTT); (2) the nanoplatform with high-energy rays (X-ray) absorption and auger electrons generation acts as a radiosensitizer for radiotherapy; (3) good photocatalytic property and large surface area make AuNCs-HA a photosensitive agent for photodynamic therapy (PDT). In vivo results demonstrated that AuNCs-HA presented excellent PA imaging performance after intravenous injection, which provided contour, size, and location information of the tumor. Moreover, because AuNCs-HA could combine radiotherapy and phototherapy together, the tumors treated with AuNCs-HA showed complete growth inhibition, comparing to that with each therapy alone. Taken together, our present study demonstrates that AuNCs-HA is of great potential as a multifunctional nanoplatform for PA imaging-guided radio- and photo-therapy of tumor. Statement of Significance In this study, a commendable theranostic nanoplatform based on hyaluronic acid modified AuNCs (AuNCs-HA) was developed. In our approach, the dilute solution of Gold(III) chloride is slowly dripped into Ag nanocubes solution, then the Au nanocages were obtained by redox reaction, and followed by HA modification. We explored them, simultaneously, as radiosensitizers for RT, photosensitizers for PDT, and therapeutic agents for PTT. Compared to that of each therapies alone, the combination of radio-therapy and photo-therapy results in a considerably improved tumor eliminating effect and efficiently inhibited tumor growth. In addition, AuNCs-HA exhibited remarkably strong PA signals for precise identification of the location, size, and boundary of the tumor, thereby facilitating imaging-guided therapy. In brief, our design of AuNCs-HA represents a general and versatile strategy for building up cancer-targeted nanotheranostics with desired synergistic imaging and therapy functionalities. [ABSTRACT FROM AUTHOR]

Purpose: Auger electrons emitted by radioisotopes such as 125I have a high linear energy transfer and short mean-free path in tissue (<10 μm), making them suitable for treating micrometastases while sparing normal tissues. The authors developed and subsequently investigated a cancer cell-selective small molecule phospholipid ether analog to deliver 125I to triple-negative breast cancer (TNBC) cells in vivo.Methods: A Current Good Manufacturing Practice (cGMP) method to radiolabel 125I-CLR1404 (CLR 125) with >95% radiochemical purity was established. To estimate CLR 125 in vivo dosimetry and identify dose-limiting organs, the biodistribution of the analog compound 124I-CLR1404 (CLR 124) was investigated using micro-positron emission tomography (PET)/computed tomography (CT) in conjunction with a Monte Carlo dosimetry platform to estimate CLR 125 dosimetry. In vivo antitumor efficacy was tested by injecting nude mice bearing either MDA-MB-231-luc orthotopic xenografts or lung metastases with 74 MBq (3.7 GBq/kg) of CLR 125 or an equivalent mass amount of nonradiolabeled CLR 125. Longitudinal tumor measurements using calipers and bioluminescence imaging were obtained for the xenografts and lung metastases, respectively.Results: Dosimetry analysis estimated that CLR 125 would impart the largest absorbed dose to the tumor per injected activity (0.261 ± 0.023 Gy/MBq) while the bone marrow, which is generally the dose-limiting organ for CLR1404, appears to have the lowest (0.063 ± 0.005 Gy/MBq). At administered activities of up to 74 MBq (3.7 GBq/kg), mice did not experience signs of toxicity. In addition, a single dose of CLR 125 reduced the volume of orthotopic primary TNBC xenografts by ∼60% compared to control vehicle (p < 0.001) and significantly extended survival. In addition, CLR 125 was efficacious against preclinical metastatic TNBC models by inhibiting the progression of micrometastases (p < 0.01).Conclusions: Targeted radionuclide therapy with CLR 125 displayed significant antitumor efficacy in vivo, suggesting promise for treatment of TNBC micrometastases. [ABSTRACT FROM AUTHOR]

Nuclear excitation functions for proton induced reactions on antimony targets have been measured up to 68 MeV using stacked foil activation techniques at the Crocker Laboratory of the University of California at Davis. Measurements made are expected to be useful in production of therapeutic radionuclides 119 Sb (via production of its parents 119m Te and 119g Te) and 117m Sn. This work extends the energy coverage of available data upwards by approximately 30 MeV into a range relevant to medium-energy radionuclide production facilities like the Isotope Production Facility in Los Alamos, New Mexico and the Brookhaven Linear Isotope Producer in Upton, New York. [ABSTRACT FROM AUTHOR]

Introduction Gold nanoparticles (AuNP; 30 nm) were modified with polyethylene glycol (PEG) chains linked to trastuzumab for binding to HER2-positive breast cancer (BC) cells and diethylenetriaminepentaacetic acid (DTPA) for complexing the Auger electron-emitter, 111 In (trastuzumab-AuNP- 111 In). Our objective was to determine the cytotoxicity of trastuzumab-AuNP- 111 In on HER2-positive BC cells in vitro and evaluate its tumor growth inhibition properties and normal tissue toxicity in vivo following intratumoral (i.t.) injection in mice with s.c. HER2-overexpressing BC xenografts. Methods Binding and internalization of trastuzumab-AuNP- 111 In or non-targeted AuNP- 111 In in SK-BR-3 (1–2 × 10 6 HER2/cell) and MDA-MB-361 (5 × 10 5 HER2/cell) human BC cells were studied. The surviving fraction (SF) of SK-BR-3 or MDA-MB-361 cells exposed to trastuzumab-AuNP- 111 In or AuNP- 111 In was determined. DNA double-strand breaks (DSBs) were assayed by probing for γ-H2AX. Tumor growth was monitored over 70 days in CD1 athymic mice with s.c. MDA-MB-361 xenografts after i.t. injection of 10 MBq (0.7 mg; 2.6 × 10 12 AuNP) of trastuzumab-AuNP- 111 In and normal tissue toxicity was assessed by monitoring body weight, complete blood cell (CBC) counts and serum alanine aminotransferase (ALT) and creatinine (Cr). Results Trastuzumab-AuNP- 111 In was specifically bound by SK-BR-3 and MDA-MB-361 cells. Trastuzumab-AuNP- 111 In was more efficiently internalized than AuNP- 111 In and localized to a peri-nuclear region. The SF fraction of SK-BR-3 cells was reduced by 1.8-fold by treatment with 3 nM (7 MBq/mL) of trastuzumab-AuNP- 111 In. The SF of MDA-MB-361 cells was reduced by 3.7-fold at 14.4 nM (33.6 MBq/mL). In comparison, non-targeted AuNP- 111 In at these concentrations reduced the SF of SK-BR-3 or MDA-MB-361 cells by 1.2-fold ( P = 0.03) and 1.7-fold ( P < 0.0001), respectively. DNA DSBs were greater in SK-BR-3 and MDA-MB-361 cells exposed to trastuzumab-AuNP- 111 In compared to AuNP- 111 In, but unlabeled trastuzumab-AuNP did not increase DNA DSBs. Local i.t. injection of trastuzumab-AuNP- 111 In in CD1 athymic mice with s.c. MDA-MB-361 tumors arrested tumor growth for 70 days. There was no apparent normal tissue toxicity. The radiation absorbed dose deposited in the tumor by trastuzumab-AuNP- 111 In was 60.5 Gy, while normal organs received <0.9 Gy. Conclusion These results are promising for further development of trastuzumab-AuNP- 111 In as a novel Auger electron-emitting radiation nanomedicine for local treatment of HER2-positive BC. Advances in knowledge and implications for patient care A local radiation treatment for HER2-positive BC based on AuNP modified with trastuzumab and labeled with the Auger electron-emitter, 111 In was developed and shown to arrest tumor growth with no normal tissue toxicity. [ABSTRACT FROM AUTHOR]

To identify the emergence of the recognition of the potential of the Auger effect for clinical application, and after tracing the salient milestones towards that goal, to evaluate the status quo and future prospects. It was not until 40 years after the discovery of Auger electrons, that the availability of radioactive DNA precursors enabled the biological power, and the clinical potential, of the Auger effect to be appreciated. Important milestones on the path to clinical translation have been identified and reached, but hurdles remain. Nevertheless the potential is still evident, and there is reasonable optimism that the goal of clinical translation is achievable. [ABSTRACT FROM PUBLISHER]

Purpose DNA ligands labelled with 125I induce cytotoxic DNA double-strand breaks (DSB), suggesting a potential for Auger endoradiotherapy. Since the 60-day half-life of 125I is suboptimal for therapy, we have investigated another Auger-emitter 124I, with shorter half-life (4.18 days), and the additional feature of positron-emission, enabling positron emission tomography (PET) imaging. The purpose of this study was to compare the two radionuclides on the basis of DNA DSB per decay. Materials and methods Using a 124I- (or 125I)-labelled minor groove binding DNA ligand, we investigated DNA breakage using the plasmid DNA assay. Biodistribution of the conjugate of the labelled ligand with transferrin was investigated in nude mice bearing a K562 human lymphoma xenograft. Results The probability of DSB per decay was 0.58 and 0.85 for 124I and 125I, respectively, confirming the therapeutic potential of the former. The crystal structure of the ligand DNA complex shows the iodine atom deep within the minor groove, consistent with the high efficiency of induced damage. Biodistribution studies, including PET imaging, showed distinctive results for the conjugate, compared to the free ligand and transferrin, consistent with receptor-mediated delivery of the ligand. Conclusions Conjugation of 124I-labelled DNA ligands to tumor targeting peptides provides a feasible strategy for Auger endoradiotherapy, with the advantage of monitoring tumor targeting by PET imaging. [ABSTRACT FROM AUTHOR]

In this work was proposed a new radiotherapy enhancement method consisting of the administration of magnetic nanoparticles into the cells with further irradiation with a gamma-ray beam. As a result, adjusting the energy distribution of a gamma-ray beam and Fe abundance it is possible to achieve an extremely intensive electron emission because of a nuclear resonance. The produced conversion and Auger electrons can be used as an effective tool for DNA lesions production. We developed a Monte Carlo model for an electron and gamma emission by Fe nucleus using the Geant4 program package. The parameters of a resonant absorption were taken from Mössbauer spectra of magnetite nanoparticles synthesized for the administration into live cells. The space distribution of the radiation dose showed an increase in the dose of 2-2.5 times in the case of the natural abundance and more than 50 times in the case of the 66 % enrichment of the nanoparticles. [ABSTRACT FROM AUTHOR]

Auger electrons-emitting radioisotopes (such as iodine-125) are a potentially effective cancer treatment. They are extremely biologically effective, but only within a short range (nanometers). Their use as an effective cancer therapy requires that they will be transported within close proximity of DNA by an intercalator, where they induce double-strand breaks leading to cell death. This type of therapy may be even more beneficial when associated with drug delivery systems. In this report, we describe an optimized triple-targeted polymer delivery system for the intercalator ellipticine, which contains radioisotope iodine-125 with high specific radioactivity (63.2 GBq/mg). This compound is linked to an N -(2-hydroxypropyl)methacrylamide copolymer via an optimized acid-sensitive hydrazone linker. The system is stable at pH 7.4 (representing the pH of blood plasma), and the radioiodine-containing biologically active intercalator is released upon a decrease in pH (44% of the intercalator is released after 24 h of incubation in pH 5.0 buffer, which mimics the pH in late endosomes). The active compound is a potent intercalator, as shown with direct titration with a DNA solution, and readily penetrates into cell nuclei, as observed by confocal microscopy. Its polymer conjugate is internalized into endosomes and releases the radioactive intercalator, which accumulates in the cell nuclei. In vivo experiments on mice with 4T1 murine breast cancer resulted in a statistically significant increase in the survival of mice treated with the polymer radioconjugate. The free radiolabeled intercalator was also shown to be effective, but it was less potent than the polymer conjugate. [ABSTRACT FROM AUTHOR]

A new efficient type of gadolinium-based theranostic agent (AGulX®) has recently been developed for MRI-guided radiotherapy (RT). These new particles consist of a polysiloxane network surrounded by a number of gadolinium chelates, usually 10. Owing to their small size (< 5 nm), AGulX typically exhibit biodistributions that are almost ideal for diagnostic and therapeutic purposes. For example, although a significant proportion of these particles accumulate in tumours, the remainder is rapidly eliminated by the renal route. In addition, in the absence of irradiation, the nanoparticles are well tolerated even at very high dose (10 times more than the dose used for mouse treatment). AGulX particles have been proven to act as efficient radiosensitizers in a large variety of experimental in vitro scenarios, including different radioresistant cell lines, irradiation energies and radiation sources (sensitizing enhancement ratio ranging from 1.1 to 2.5). Pre-clinical studies have also demonstrated the impact of these particles on different heterotopic and orthotopic tumours, with both intratumoural or intravenous injection routes. A significant therapeutical effect has been observed in all contexts. Furthermore, MRI monitoring was proven to efficiently aid in determining a RT protocol and assessing tumour evolution following treatment. The usual theoretical models, based on energy attenuation and macroscopic dose enhancement, cannot account for all the results that have been obtained. Only theoretical models, which take into account the Auger electron cascades that occur between the different atoms constituting the particle and the related high radical concentrations in the vicinity of the particle, provide an explanation for the complex cell damage and death observed. [ABSTRACT FROM AUTHOR]

Abstract: This article pioneers a study into the influence of the high-Z component of nanoparticles on the efficacy of radioprotection some nanoparticles offer to exposed cells irradiated with X-rays. We reveal a significant decrease in the radioprotection efficacy for cells exposed to CeO2 nanoparticles and irradiated with 10MV and 150kVp X-rays. In addition, analysis of the 150kVp survival curve data indicates a change in radiation quality, becoming more lethal for irradiated cells exposed to CeO2 nanoparticles. We attribute the change in efficacy to an increase in high linear energy transfer Auger electron production at 150kVp which counterbalances the CeO2 nanoparticle radioprotection capability and locally changes the radiation quality. This study highlights an interesting phenomenon that must be considered if radiation protection drugs for use in radiotherapy are developed based on CeO2 nanoparticles. From the Clinical Editor: CeO2 nanoparticles are thought to offer radioprotection; however, this study reveals significant decrease in the radioprotection efficacy for cells exposed to CeO2 nanoparticles and irradiated with 10 MV and 150 kVp X-rays. This phenomenon must be considered when developing radiation protection drugs based on CeO2 nanoparticles. [Copyright &y& Elsevier]

Use of radiometals in nuclear oncology is a rapidly growing field and encompasses a broad spectrum of radiotracers for imaging via PET (positron emission tomography) or SPECT (single-photon emission computed tomography) and therapy viaα, β−, or Auger electron emission. This feature article opens with a brief introduction to the imaging and therapy modalities exploited in nuclear medicine, followed by a discussion of the multi-component strategy used in radiopharmaceutical development, known as the bifunctional chelate (BFC) method. The modular assembly is dissected into its individual components and each is discussed separately. The concepts and knowledge unique to metal-based designs are outlined, giving insight into how these radiopharmaceuticals are evaluated for use in vivo. Imaging nuclides 64Cu, 68Ga, 86Y, 89Zr, and 111In, and therapeutic nuclides 90Y, 177Lu, 225Ac, 213Bi, 188Re, and 212Pb will be the focus herein. Finally, key examples have been extracted from the literature to give the reader a sense of breadth of the field. [ABSTRACT FROM AUTHOR]

Abstract: Evaluation of the intracellular distribution of radionuclides used for targeted radiotherapy (tRT) is essential for accurate dosimetry. Therefore, a direct and quantitative method for subcellular micro-autoradiography using radiation sensitive polymers (PMMA, UV1116 and AZ40XT) was developed. The electron exposure dose in radio-labelled cells due to Auger and internal conversion (IC) electron emissions of indium (111In), a radionuclide currently used for tRT, was calculated using Monte Carlo (MC) simulation. Electron beam lithography using pre-defined exposure doses was used to calibrate the resist response. The topography of the exposed and developed resists was analysed with atomic force microscopy (AFM) and the resulting pattern depth was related to a specific exposure dose. UV1116 exhibited the best contrast as compared to AZ40XT and PMMA, while AZ40XT exhibited the highest sensitivity at low doses (<10μC/cm2). AFM analysis of the exposure pattern from radio-labelled cells and nuclei in UV1116 revealed a non-uniform distribution of 111In-EGF in the cell and nucleus, consistent with less well-resolved data from confocal microscopy and micro-autoradiography. [Copyright &y& Elsevier]

Auger electron emitting radionuclides in cancer therapy offer the opportunity to deliver a high radiation dose to the tumor cells with high radiotoxicity while minimizing toxicity to normal tissue. We have in this study identified the Auger emitter 119Sb as a potent nuclide for targeted radionuclide therapy based on theoretical dosimetry calculations at a subcellular scale. From these calculations we have determined the cellular S-values for this therapeutic isotope. Moreover, we have demonstrated the possibility of producing this isotope and also the SPECT-analogue 117Sb for patient-specific dosimetry, by measuring the proton irradiation yields for both isotopes using a low-energy cyclotron. The excellent SPECT imaging properties of the 117Sb radionuclide have been shown by scanning a Jaszczak SPECT Phantom. [ABSTRACT FROM AUTHOR]