Impact of dose distribution by a 3D planning system for brachytherapy with 198Au grains for head and neck cancer.

BACKGROUND: There has been no study in which the correlation between clinical results and dosimetry based on a 3D treatment planning system in patients with 198Au grains for head and neck cancer was evaluated. METHODS: Thirty-two patients who were treated with 198Au grains for head and neck cancer were reviewed. Twenty-five patients were treated with brachytherapy alone and seven patients were treated with a combination of brachytherapy and neoadjuvant external beam radiation therapy. RESULTS: With a median observation period of 60 months, the 5-year local control rate was 82.9%. V85Gy of CTV in patients with local recurrence tended to be lower than that in patients without local recurrence (p = 0.07). The maximum dose of the keratinized gingiva in patients in whom bone exposure occurred was significantly higher than that in patients in whom bone exposure did not occur (p = 0.001). CONCLUSIONS: Dose distribution with 198Au grains can predict local control and late adverse events.

Radiation doses of medical radiation workers performing low-dose-rate brachytherapy with 198Au grains and 192Ir pins for patients with oral cancers.

OBJECTIVES: Low-dose-rate brachytherapy (LDR-BT) with 198Au grains and 192Ir pins is an essential treatment option for oral cancer due to its high rate of local control and low invasiveness. However, the radiation exposure of medical radiation workers is concerning. Thus, we aimed to determine the radiation dose delivered to medical radiation workers during LDR-BT using 198Au grains and 192Ir pins for oral cancer. METHODS: Thirty-two patients with oral cancer underwent 198Au grain interstitial LDR-BT between June 2016 and May 2023, and 23 patients with tongue cancer underwent 192Ir pin interstitial LDR-BT between March 2015 and November 2017 at our hospital. Dosimetry was performed by attaching a dosimeter to the chest pocket of the operator and assistant during 198Au grain or 192Ir pin LDR-BT. Since the operator also loads 198Au grains into the implantation device, the operator's radiation dose includes the dose received during this preparation. RESULTS: Mean radiation doses of the operators with 198Au grain and 192Ir pin LDR-BT were 165.8 and 211.2 µSv, respectively. Statistically significant differences between the radioactive sources of 198Au grain and 192Ir pin LDR-BT were observed (p = 0.0459). The mean radiation doses of the assistants with 198Au grain and 192Ir pin LDR-BT were 92.0 and 162.0 µSv, respectively. Statistically significant differences were observed between the radioactive sources of 198Au grains and 192Ir pin LDR-BT (p = 0.0003). CONCLUSIONS: Regarding radioactive source differences, 192Ir pin LDR-BT resulted in higher doses delivered to medical radiation workers than 198Au grain LDR-BT.

Radiosynthesis of Stable 198Au-Nanoparticles by Neutron Activation of αvß3-Specific AuNPs for Therapy of Tumor Angiogenesis.

This paper reports on the development of stable tumor-specific gold nanoparticles (AuNPs) activated by neutron irradiation as a therapeutic option for the treatment of cancer with high tumor angiogenesis. The AuNPs were designed with different mono- or dithiol-ligands and decorated with different amounts of Arg-Gly-Asp (RGD) peptides as a tumor-targeting vector for αvß3 integrin, which is overexpressed in tissues with high tumor angiogenesis. The AuNPs were evaluated for avidity in vitro and showed favorable properties with respect to tumor cell accumulation. Furthermore, the therapeutic properties of the [198Au]AuNPs were evaluated in vitro on U87MG cells in terms of cell survival, suggesting that these [198Au]AuNPs are a useful basis for future therapeutic concepts.

Harnessing Nuclear Energy to Gold Nanoparticles for the Concurrent Chemoradiotherapy of Glioblastoma.

Nuclear fission reactions can release massive amounts of energy accompanied by neutrons and γ photons, which create a mixed radiation field and enable a series of reactions in nuclear reactors. This study demonstrates a one-pot/one-step approach to synthesizing radioactive gold nanoparticles (RGNP) without using radioactive precursors and reducing agents. Trivalent gold ions are reduced into gold nanoparticles (8.6-146 nm), and a particular portion of 197Au atoms is simultaneously converted to 198Au atoms, rendering the nanoparticles radioactive. We suggest that harnessing nuclear energy to gold nanoparticles is feasible in the interests of advancing nanotechnology for cancer therapy. A combination of RGNP applied through convection-enhanced delivery (CED) and temozolomide (TMZ) through oral administration demonstrates the synergistic effect in treating glioblastoma-bearing mice. The mean survival for RGNP/TMZ treatment was 68.9 ± 9.7 days compared to that for standalone RGNP (38.4 ± 2.2 days) or TMZ (42.8 ± 2.5 days) therapies. Based on the verification of bioluminescence images, positron emission tomography, and immunohistochemistry inspection, the combination treatment can inhibit the proliferation of glioblastoma, highlighting the niche of concurrent chemoradiotherapy (CCRT) attributed to RGNP and TMZ.

Effectiveness of Spacers in Brachytherapy With 198Au Grains for Patients With Buccal Mucosa Cancer.

BACKGROUND/AIM: The aim of this study was to investigate the use of spacers and their efficacy in brachytherapy with 198Au grains for buccal mucosa cancer. PATIENTS AND METHODS: Sixteen patients with squamous cell carcinoma of the buccal mucosa who were treated with 198Au grain brachytherapy were included. The distance between 198Au grains, distance between 198Au grains and the maxilla or mandible, and the maximum dose/cc to the jawbone (D1cc) with and without a spacer was investigated in three out of 16 patients. RESULTS: The median distance between 198Au grains without and with a spacer was 7.4 and 10.7 mm, respectively; this was significantly different. The median distance between 198Au grains and the maxilla without and with a spacer was 10.3 and 18.5 mm, respectively; again this was significantly different. The median distance between 198Au grains and the mandible without and with a spacer was 8.6 and 17.3 mm, respectively; the difference was significant. The D1cc to the maxilla without and with a spacer were 14.9, 68.7, and 51.8 Gy and 7.5, 21.2, and 40.7 Gy in cases 1, 2, and 3, respectively. The D1cc to the mandible without and with a spacer were 27.5, 68.7, and 85.8 Gy and 11.3, 53.6, and 64.9 Gy in cases 1, 2, and 3, respectively. No osteoradionecrosis of the jaw bones was observed in any case. CONCLUSION: The spacer enabled maintenance of the distance between 198Au grains, and between 198Au grains and the jawbone. In buccal mucosa cancer, using a spacer in brachytherapy with 198Au grains appears to reduce jawbone complications.

198Au-Coated Superparamagnetic Iron Oxide Nanoparticles for Dual Magnetic Hyperthermia and Radionuclide Therapy of Hepatocellular Carcinoma.

This study was performed to synthesize a radiopharmaceutical designed for multimodal hepatocellular carcinoma (HCC) treatment involving radionuclide therapy and magnetic hyperthermia. To achieve this goal, the superparamagnetic iron oxide (magnetite) nanoparticles (SPIONs) were covered with a layer of radioactive gold (198Au) creating core-shell nanoparticles (SPION@Au). The synthesized SPION@Au nanoparticles exhibited superparamagnetic properties with a saturation magnetization of 50 emu/g, which is lower than reported for uncoated SPIONs (83 emu/g). Nevertheless, the SPION@Au core-shell nanoparticles showed a sufficiently high saturation magnetization value which allows them to reach a temperature of 43 °C at a magnetic field frequency of 386 kHz. The cytotoxic effect of nonradioactive and radioactive SPION@Au-polyethylene glycol (PEG) bioconjugates was carried out by treating HepG2 cells with various concentrations (1.25-100.00 µg/mL) of the compound and radioactivity in range of 1.25-20 MBq/mL. The moderate cytotoxic effect of nonradioactive SPION@Au-PEG bioconjugates on HepG2 was observed. The cytotoxic effect associated with the ß- radiation emitted by 198Au was much greater and already reaches a cell survival fraction below 8% for 2.5 MBq/mL of radioactivity after 72 h. Thus, the killing of HepG2 cells in HCC therapy should be possible due to the combination of the heat-generating properties of the SPION-198Au-PEG conjugates and the radiotoxicity of the radiation emitted by 198Au.

Photonuclear Alchemy: Obtaining Medical Isotopes of Gold from Mercury Irradiated on Electron Accelerators.

In our work, the photonuclear production of 198,199Au isotopes for nuclear medicine purposes was studied, and a method for their recovery from irradiated mercury was developed. The yields of the corresponding nuclear reactions were determined, and a comparison of various methods of obtaining gold radioisotopes was provided. New sorbents based on benzo-15-crown-5, which selectively binds gold, were studied, and the optimal conditions for Au recovery with a high degree of purification from mercury were found. It was established that, for the fast and quantitative recovery of Au isotopes, it was necessary to add at least 0.1 mg of the carrier. As a result, the developed method can be regularly used to obtain 198,199Au for the research of radiopharmaceuticals based on them.

Brachytherapy with 198Au grains for cancer of the floor of the mouth: relationships between radiation dose and complications.

OBJECTIVE: This study aimed to retrospectively evaluate the radiation dose and complications in soft tissue and mandible caused by 198Au grain brachytherapy alone or the combination with other modalities in patients with the cancer of the floor of the mouth. MATERIALS AND METHODS: Twelve patients with T1 (n = 5) and T2 (n = 7) squamous cell carcinoma of the floor of the mouth, who were treated with 198Au grain brachytherapy alone (n = 5) or the combination of external beam radiotherapy (EBRT) and/or chemotherapy and 198Au grain brachytherapy (n = 7) from January 2005 to December 2016, were included. The relationships between the radiation dose and the complications of the soft tissue or mandible were investigated. RESULTS: Seven of 12 patients had died. Of these 7 patients, one with T1 and 2 with T2 had died of the causes related to the cancer of the floor of the mouth. Two with T1 and 2 with T2 had died of other diseases. Two patients had grade 2 complications of the soft tissue and mandible. These patients were treated by the combination of EBRT and/or chemotherapy and 198Au grain brachytherapy and irradiated with 123 or 139 Gy in total dose, respectively. And one of these patients was treated by the chemotherapy in addition to EBRT. CONCLUSION: Our study showed that the combination of EBRT and 198Au grains brachytherapy for the floor of the mouth cancer patients might be associated with risks of developing complications of soft tissue ulcer and mandibular bone necrosis.

Dose characteristics of Au-198 eye brachytherapy applicator: A Monte Carlo study.

PURPOSE: The use of ocular plaques is a promising treatment option for eye melanoma brachytherapy. Although several studies have been done on various ocular plaques, little is known about the dose characterization of 198Au plaque. MATERIALS AND METHOD: The full mathematical model of the eye phantom, tumor, 106Ru/106Rh CCA, and 198Au plaque were simulated using the Monte Carlo MCNPX code. The dose distribution was measured in the plaque's central axis direction, and a dose profile was also measured at a distance of 2.5 mm from the plaque surface. RESULTS: The findings showed that 198Au plaque has superior dosimetric characteristics than CCA plaque for tumors with a thickness of greater than 3.5 mm, while CCA plaque is better for tumors with a thickness of less than 3.5 mm. The dose to the sclera and choroid is higher in the case of CCA plaque, while the dose to the organs at risk (lens and optic nerve) is greater in the case of 198Au applicator. In the case of 198Au plaque, however, the dose to sensitive organs was within their permissible dose range. CONCLUSION: In the treatment of medium and large tumors, 198Au plaque is more successful than CCA plaque. It can produce a much more homogeneous lateral dose profile in the target. In the treatment of dome-shaped tumors, 198Au plaque may be more successful than CCA plaque. As a result, the tumor's shape influences the plaque type selection.

Treatment outcomes of real-time intraoral sonography-guided implantation technique of 198Au grain brachytherapy for T1 and T2 tongue cancer.

It is often challenging to determine the accurate size and shape of oral lesions through computed tomography (CT) or magnetic resonance imaging (MRI) when they are very small or obscured by metallic artifacts, such as dental prostheses. Intraoral ultrasonography (IUS) has been shown to be beneficial in obtaining precise information about total tumor extension, as well as the exact location and guiding the insertion of catheters during interstitial brachytherapy. We evaluated the role of IUS in assessing the clinical outcomes of interstitial brachytherapy with 198Au grains in tongue cancer through a retrospective medical chart review. The data from 45 patients with T1 (n = 21) and T2 (n = 24) tongue cancer, who were mainly treated with 198Au grain implants between January 2005 and April 2019, were included in this study. 198Au grain implantations were carried out, and positioning of the implants was confirmed by IUS, to ensure that 198Au grains were appropriately placed for the deep border of the tongue lesion. The five-year local control rates of T1 and T2 tongue cancers were 95.2% and 95.5%, respectively. We propose that the use of IUS to identify the extent of lesions and the position of implanted grains is effective when performing brachytherapy with 198Au grains.

Clinical scale synthesis of intrinsically radiolabeled and cyclic RGD peptide functionalized 198Au nanoparticles for targeted cancer therapy.

INTRODUCTION: The emerging concept of intrinsically radiolabeled nanoparticles has the potential to transform the preclinical and clinical studies by improving the in vivo stability and demonstrating minimal alteration in the inherent pharmacokinetics of the nanoparticles. In this paper, a simple and efficient single-step method for clinical scale synthesis of intrinsically radiolabeled 198Au nanoparticles conjugated with cyclic arginine-glycine-aspartate peptide (198AuNP-RGD) is reported for potential use in targeted cancer therapy. METHODS: Large radioactive doses (>37 GBq) of 198AuNP-RGD were synthesized by reaction of 198Au-HAuCl4 with cyclic RGD peptide. The synthesized nanoparticles were characterized by various analytical techniques. In vitro cell binding studies were carried out in B16F10 (murine melanoma) cell line. Biodistribution studies were carried out in melanoma tumor bearing C57BL/6 mice to demonstrate the tumor targeting ability of 198AuNP-RGD. The therapeutic efficacy of 198AuNP-RGD was evaluated by carrying out systematic tumor regression studies in melanoma tumor bearing mice after intravenous administration of the radioactive doses. RESULTS: Well dispersed and biocompatible nanoparticles (~12.5 nm diameter) could be synthesized with excellent radiochemical and colloidal stability. In vitro studies exhibited the cell binding affinity and specificity of 198AuNP-RGD towards melanoma cell line. A high uptake of 8.7 ±â€¯2.1%ID/g in the tumor was observed within 4 h post-injection (p.i.). Significant decrease in tumor uptake of 198AuNP-RGD (2.9 ±â€¯0.8%ID/g) at 4 h p.i. on co-injection of a blocking dose of the peptide suggested that tumor localization of the intrinsically radiolabeled nanoparticles was receptor mediated. Administration of 37.0 MBq of 198AuNP-RGD resulted in significant regression of tumor growth with no apparent body weight loss over a period of 15 d. CONCLUSIONS: Overall, these promising results demonstrate the suitability of 198AuNP-RGD as an advanced functional nanoplatform for targeted cancer therapy.

Internalization capabilities of gold-198 nanoparticles: Comparative evaluation of effects of chitosan agent on cellular uptake into MCF-7.

In this study, internalization of positively charged chitosan-coated nanoparticles (198AuNPs@chitosan) on MCF-7 cells was investigated by γ-ray spectroscopy and then statistically compared to that of 198Au and negatively charged citrate-stabilized nanoparticles (198AuNPs). Sub-50 nm 198AuNPs@chitosan had a higher internalization compared to 198Au and 198AuNPs (p < 0.05). More cellular uptake of 198AuNP@chitosan means a higher dose of radioactivity to the tumor cells which, in turn, more effective treatment of the cancer.

In vitro Cytotoxicity Effects of 197Au/PAMAMG4 and 198Au/PAMAMG4 Nanocomposites Against MCF7 and 4T1 Breast Cancer Cell Lines.

Purpose: Study on gold based therapeutic agents for cancer cells deracination has become under scrutiny in recent years owing to effective treatments are not available for rapidly progressive cancers. The aim of present study was to examine efficiency of radioactive 198Au/PAMAMG4 and non-radioactive 197Au/PAMAMG4 nancomposites against 4T1 and MCF7 breast cancer cell lines. Methods: The PAMAMG4 dendrimer was treated with the gold anions and then, the mixture was chemically reduced by NaBH4. Prepared 197Au/PAMAMG4 was bombarded by thermal neutrons in the Tehran Research Reactor to 198Au/PAMAMG4 be produced. Prepared nanocomposites were characterized by means of FT-IR, 1H NMR, Zeta-potential measurements, TEM and EDX analyses. The radionuclidic purity of the 198Au/PAMAMG4 solution was determined using purity germanium (HPGe) spectroscopy and its stability in the presence of human serum was studied. In vitro studies were carried out to compare toxicity of PAMAMG4, 197Au/PAMAMG4 and 198Au/PAMAMG4 towards 4T1 and MCF7 cancerous cells and C2C12 normal cell lines. Results: Characterization results exhibited that invitro agents, 197Au/PAMAMG4 and 198Au/PAMAMG4, were synthesized successfully. Cells viability after 24 h, 48 h, and 72 h incubation, using MTT assay showed that the toxicity of 198Au/PAMAMG4 is significantly superior in comparison with 197Au/PAMAMG4 and PAMAMG4. Furthermore, the toxicity of 198Au/PAMAMG4 was higher on cancerous cells especially in higher level of concentrations after 72 hours (P<0.05). Conclusion: In the current study, the preparation of 197Au/PAMAMG4 and 198Au/PAMAMG4 is described and the cytotoxic properties of them against the MCF7, 4T1 cancerous cells and C2C12 normal cells were evaluated using MTT assay.

Absolute measurement of (198)Au activity in gold foil using plastic scintillators and a well-type NaI(Tl) detector.

A beta-gamma coincidence system has been developed for measuring (198)Au activity in gold foils. The system was validated by Monte Carlo simulations and by measuring the activity of a (60)Co point-source. To study effects such as self-shielding of beta particles in gold foils, (198)Au activity measurements and simulations were performed for various scintillators and foil sizes. The measured (198)Au activities were ~1% above the reference activity, which might be due to self-shielding of beta particles. The measured and simulated (198)Au activities agreed, suggesting feasibility of precise activity measurement.

Biodistribution (as determined by the radiolabelled equivalent) of a gold(III) bis(pyrrolide-imine) Schiff base complex: a potential chemotherapeutic.

The biodistribution of an N2 N2 ' tetradentate gold(III) chelate, which is known to be cytotoxic towards a range of human cancer cell lines, was determined by a radiolabelled equivalent of the compound. The (198) Au-labelled gold(III) chelate of a bis(pyrrolide-imine) Schiff base ligand with a three-carbon di(azomethine) linkage was successfully synthesised with a high radiochemical yield of 73% and radiochemical purity of >95%. The high energy γ-ray emitted by the (198) Au nucleus was used to follow the biodistribution of the compound in vivo in six male Sprague Dawley rats on a gamma camera. The log Po/w value of the (nat) Au analogue, -1.92(2), showed that the compound is hydrophilic and therefore likely to largely remain in the blood pool. This was confirmed by the biodistribution study, which showed 21% of the injected dose (ID) remained in the blood pool 4.5 h after injection. This decreased to 10.8% over a 24-h period. The activity measured in the lungs, 1.48%ID/g, remained relatively constant over a 24-h period suggesting that the complex had accumulated in the lungs in the form of particulates, and could not be cleared by the test subjects. The t½ for the heart and lungs was greater than 24 h. Excretion of the test compound is seemingly via the kidneys, but is slow with approximately 30% of the ID excreted within 24 h.

198Au grain implantation for early tongue cancer in patients of advanced age or poor performance status.

Brachytherapy using (198)Au grains is minimally invasive and the only curative treatment for early tongue cancer in patients of advanced age or poor performance status available in our institution. From March 1993 to February 2008, (198)Au grains were used to treat a group of 96 Stage I-II tongue cancer patients who could not undergo surgery or brachytherapy using (192)Ir pins because of an advanced age (≥75 years) or poor performance status (≥2). The patients were followed for 3.9 ± 3.3 years, and the cause-specific survival and local control rates were determined. Survival analyses were performed using the Kaplan-Meier method, and univariate and multivariate analyses were performed using the Cox proportional hazard model. The results were compared with those for a group of 193 early tongue-cancer patients who underwent treatment using iridium pins. The 5-year cause-specific survival and local control rates of the (198)Au grains group were 71% and 68%, respectively, both of which were 16% lower than the corresponding rates for the (192)Ir pins group. Our study demonstrated that as the last curative treatment available, (198)Au grain implantation could be used to achieve moderate treatment results for early tongue cancer in patients of advanced age or poor performance status.

Effects of Colloidal Gold 198Au on Synovial Membrane of Rabbits / 대한정형외과학회잡지

Colloidal gold 198Au were injected into 40 knee joints of rabbits for the study of the change of synovial membrane. We verified even distribution of Colloidal gold 198Au about knee joints by use of scintigraphy. After then, histopathological examinations were performed by periodic intervals. The following results are obtained form this study. l. Intra-articular injection of Colloidal gold 198Au into rabbit's knee joints resulted in a mild resctive inflammation at synovium. In was charscterized by an infiltration of eosinophils and by sclerotic changes in the subsynovium and by fibrosis of synovial vessels. 2. From this study, intra-articular injection of Colloidal gold 198Au may by benefit to treat the chronic synovial effusion in human.