Preparation and Evaluation of Thermosensitive Liposomes Encapsulating I-125-Labeled Doxorubicin Derivatives for Auger Electron Therapy.

Auger electrons (AEs) are very low-energy electrons emitted by radionuclides such as I-125 (125I). This energy is deposited across a small distance (<0.5 µm), resulting in high linear energy transfer that is potent for causing lethal damage to cancer cells. Thus, AE-emitting radiotherapeutic agents have great potential for cancer treatment. In this study, thermosensitive liposomes (TSLs) encapsulating 125I-labeled doxorubicin (DOX) derivatives were developed for Auger electron therapy, targeting the DNA of cancer cells. A radioiodinated DOX derivative [125I]5 highly accumulated in the nuclei of cancer cells and showed potent cytotoxicity against Colon 26 cancer cells by AEs. Subsequently, [125I]5 was loaded into the TSLs with high encapsulation efficiency. Potent release of [125I]5 from TSLs was achieved with heating, whereas a decreased release was observed without heating. Furthermore, TSLs encapsulating [125I]5 showed a high uptake in the nuclei at 42 °C for 1 h. We supposed that [125I]5 was released by heating at 42 °C and accumulated in the nuclei in the cells. These results suggest that the combination of TSLs encapsulating [125I]5 and hyperthermia is an effective cancer therapy.

Relationship between changes in quality of life and genitourinary toxicity grade after brachytherapy with I-125 alone for localised prostate cancer.

Background: The relationship between the grading of toxicities based on toxicity criteria and longitudinal changes in quality of life (QOL) scores after permanent prostate brachytherapy (PPB) for localized prostate cancer remains unclear. This study aimed to evaluate these relationships. Materials and methods: We assessed 107 patients treated with PPB using Iodine-125 alone from May 2007 to April 2010. Disease-specific QOL scores before PPB and at 1, 3, 6, 12, and 24 months after PPB were retrospectively evaluated with the Expanded Prostate Cancer Index Composite (EPIC), focusing on urinary domains. Toxicities were graded using the Radiation therapy oncology group and the European organization for research and treatment of cancer toxicity criteria. Results: The median follow-up duration was 116 (range 18-148) months. Thirty-four patients (31.8%) developed grade ≥ 2 acute genitourinary (GU) toxicities; six (5.6%) developed grade ≥ 2 late GU toxicities. The general urinary domain score dropped significantly at 1 month (77.1 ± 14.1) post-PPB compared to the baseline score (92.2 ± 8.2), and then gradually returned to the baseline level by 12 months (93.7 ± 8.3) post-PPB. Reductions in the general urinary domain scores, including its subscale scores at 1, 3, and 6-months post-PPB were significantly greater among patients with grade ≥ 2 GU toxicity than among those with grade 0-1 GU toxicity. Changes in urinary domain scores demonstrated a close relationship with acute GU toxicity grades after PPB. Conclusions: Longitudinal assessments of the EPIC QOL scores provided additional information regarding time-course changes in GU toxicities after PPB.

I-125 seeds brachytherapy with transcatheter arterial chemoembolization for subcapsular hepatocellular carcinoma.

BACKGROUND: I-125 seeds brachytherapy (ISB) has been used to improve the clinical effectiveness of transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). We aim to appraise the safety and clinical efficacy of combined ISB and TACE for the treatment of subcapsular HCC. MATERIALS AND METHODS: A retrospective investigative study extending from January 2017 to December 2020, involved individuals suffering from subcapsular HCC, who were subjected to TACE treatment with or without ISB in our center. The clinical effectiveness was compared between 2 groups. RESULTS: Sixty-four patients, in total, with subcapsular HCC had to undergo TACE with (n = 32) or without (n = 32) ISB in our center. After CT-guided ISB, only 2 (6.3%) patients experienced a self-limited pneumothorax. Combined treatment resulted in a significantly higher complete response (56.3% vs. 18.8%, P = 0.002) and total response (90.7% vs. 59.4%, P = 0.004) rates than that of TACE alone. In comparison to the TACE alone group, the median progression-free survival was substantially longer in the combined treatment group (11 months vs. 5 months, P = 0.016). Further, 15 and 28 patients in combined and TACE alone groups respectively died within the follow-up. The median OS was comparable between combined and TACE alone groups (22 months vs. 18 months, P = 0.529). CONCLUSIONS: Combined TACE and ISB therapy is a safe treatment method for individuals suffering from subcapsular HCC. When compared, combined treatment had significantly enhanced clinical efficacy as a subcapsular HCC therapy, in comparison to TACE alone.

I-125 seeds insertion with TACE for advanced HCC: a meta-analysis of randomized controlled trials.

PURPOSE: To assess the effectiveness of I-125 seeds (IS) insertion with transcatheter arterial chemoembolization (TACE) in treating patients with advanced hepatocellular carcinoma (HCC). MATERIAL AND METHODS: An extensive search was conducted for relevant randomized controlled trials (RCTs) from the establishment date of each database to November 2020. RESULTS: A total of nine RCTs were included in this study. Our analysis showed no significant changes in the pooled Δalpha-fetoprotein values (p = .06), incident rates of myelosuppression (p = .46), vomit occurrence (p = .27), and abnormal liver function (p = .42) between the two treatment groups. However, the complete response (p < .00001), total response (p < .00001), and disease control (p < .00001) rates were significantly higher in patients who underwent TACE with IS insertion, as opposed to patients who received TACE alone. Furthermore, patients who underwent TACE with IS insertion experienced markedly longer pooled overall survival (OS) time (p < .0001), with better OS rates at the six-month (p = .0002), one-year (p < .0001), and three-year (p = .0003) follow-ups than patients who received TACE alone. CONCLUSION: TACE with IS insertion can significantly improve clinical response and prolong the survival of advanced HCC patients.

Salvage I-125 brachytherapy for locally-recurrent prostate cancer after radiotherapy.

PURPOSE: Retrospective, single-institution analysis of clinical outcomes and treatment-related toxicity in patients treated with salvage I-125 low-dose rate (LDR) brachytherapy (BT) for locally-recurrent prostate cancer after radiotherapy. MATERIALS AND METHODS: Between 2008 and 2018, 30 patients with biopsy-confirmed prostate cancer recurrence underwent salvage treatment with I-125 LDR-BT. Of these 30 patients, 14 were previously treated with primary external beam radiotherapy (EBRT; median dose, 73 Gy) and 16 with primary I-125 LDR-BT (145 Gy and 160 Gy in 14 and 2 cases, respectively). At seed implantation, the mean age was 75.8 years, with a median Gleason score of 7 and pre-salvage PSA of <10 ng/mL. Six patients received androgen deprivation therapy for six months after relapse diagnosis. The prescribed salvage I-125 BT dose to the gland was 120-130 Gy, with dose restrictions of Dmax <135% (urethra) and <100% (rectum). Toxicity was evaluated according to the CTCAE scale (v4.0). RESULTS: At a median follow-up of 45 months, the biochemical recurrence-free survival rates at 1, 3 and 5 years were 86.7%, 56.7% and 53.3%, respectively. Overall survival at 5 years was 87%. On the multivariate analysis, two variables were significant predictors of recurrence: PSA at relapse and nadir PSA post-salvage. Grade 3 genitourinary toxicity was observed in 5 patients (radiation-induced cystitis in 3 cases and urethral stenosis in 2) and G3 gastrointestinal toxicity in 3 patients (rectal bleeding). CONCLUSION: Salvage therapy with I-125 brachytherapy is a safe and effective treatment option for locally-recurrent prostate cancer in previously-irradiated patients. High pre-salvage PSA and post-salvage nadir PSA values were significantly associated with a worse disease control after salvage I-125 LDR-BT. In well-selected patients, I-125 LDR-BT is comparable to other salvage therapies in terms of disease control and toxicity. However, more research is needed to determine the optimal management of locally-recurrent prostate cancer.

Impact of real-time, dose-escalated permanent seed implant brachytherapy in intermediate-risk prostate cancer.

PURPOSE: To retrospectively evaluate biochemical control and toxicity in patients who underwent 125I seed brachytherapy (BT) for intermediate-risk prostate cancer (PCa). MATERIALS AND METHODS: Between January 2004-December 2014, 395 patients with intermediate-risk PCa underwent 125I BT. Of these, 117 underwent preoperative planning (PP; 145 Gy) and 278 real-time intraoperative preplanning (IoP; 160 Gy). All patients were followed for ≥ 6 months (> 5 years in 48% of patients and > 7 years in 13%). Median follow-up was 59 months. RESULTS: Biochemical relapse-free survival (BRFS) rates at 5 and 8 years were, respectively, 91.7% and 82.1%. By treatment group, the corresponding BRFS rates were 93.5% and 90% for IoP and 89% and 76.8% for PP. The maximum dose to the urethra remained unchanged (217 Gy) despite the dose escalation (from 145 to 160 Gy), without any significant increase in treatment-related toxicity (p = 0.13). Overall toxicity outcomes in the series were excellent, with only 3 cases (0.76%) of grade 3 genitourinary toxicity. CONCLUSION: The real-time intraoperative planning technique at 160 Gy yields better biochemical controls than the preoperative planning technique at 145 Gy. Dose escalation did not increase urinary toxicity. The excellent results obtained with the IoP BT technique support its use as the first treatment option in this patient population.

Comparative Evaluation of Two DARPin Variants: Effect of Affinity, Size, and Label on Tumor Targeting Properties.

Designed ankyrin repeat proteins (DARPins) are small engineered scaffold proteins that can be selected for binding to desirable molecular targets. High affinity and small size of DARPins render them promising probes for radionuclide molecular imaging. However, detailed knowledge on many factors influencing their imaging properties is still lacking. We have evaluated two human epidermal growth factor 2 (HER2)-specific DARPins with different size and binding properties. DARPins 9_29-H6 and G3-H6 were radiolabeled with iodine-125 and tricarbonyl technetium-99m and evaluated in vitro. A side-by-side comparison of biodistribution and tumor targeting was performed. HER2-specific tumor accumulation of G3-H6 was demonstrated. A combination of smaller size and higher affinity resulted in a higher tumor uptake of G3-H6 in comparison to 9_29-H6. Technetium-99m labeled G3-H6 demonstrated a better biodistribution profile than 9_29-H6, with several-fold lower uptake in liver. Radioiodinated G3-H6 showed the best tumor-to-organ ratios. The combined effect of affinity, molecular weight, scaffold composition, and nonresidualizing properties of iodine label provided radioiodinated G3-H6 with high clinical potential for imaging of HER2.

MRI-guided preoperative 125 I seed localizations: Case report.

Preoperative nonwire localizations with 125 I seeds are performed using mammographic or ultrasonographic guidance. Current MRI-guided interventions in the breast are primarily limited to biopsies and wire localizations. Occasionally, nonwire localization with 125 I seeds is preferred, but the target is only well seen on MRI. This case report describes how MRI-guided preoperative two 125 I seed bracket localization was performed.

Permanent seed implant brachytherapy in low-risk prostate cancer: Preoperative planning with 145 Gy versus real-time intraoperative planning with 160 Gy.

AIM: The present retrospective study was to compare toxicity and survival outcomes in a group of low-risk PCa patients treated with either the preoperative planning technique (145 Gy) or the real-time IoP technique (160 Gy). BACKGROUND: The two most common permanent seed implantation techniques are preoperative planning (PP) with 145 Gy and real-time intraoperative planning (IoP) with 160 Gy. Although IoP has largely replaced PP at many centres in recent years, few studies have directly compared these two techniques. MATERIALS AND METHODS: Retrospective study of 408 patients with low-risk PCa treated with permanent seed implant brachytherapy at our institution between October 2003 and December 2014. Of these, 187 patients were treated with PP at a dose of 145 Gy while 221 received real-time IoP with 160 Gy. RESULTS: At a median follow up of 90 months, 5- and 8-year rates of biochemical relapse-free survival (BRFS) were 94.8% and 86% with the IoP technique versus 90.8% and 83.9%, respectively, with PP. The maximum dose to the urethra was <217 Gy with both techniques. Despite the higher dose, IoP did not cause any significant increase in toxicity (p = 0.11). CONCLUSIONS: The present study shows that real-time intraoperative brachytherapy at a dose of 160 Gy yield better biochemical control than preoperative planning at 145 Gy. In addition, urinary toxicity did not increase, despite the dose escalation, probably because the dose constraints to the urethra were met despite the increased dose escalation. These findings support the use of real-time IoP.

Dosimetric characterization of GMS BT-125-1 125 I radioactive seed with Monte Carlo simulations and experimental measurement.

PURPOSE: To investigate the dosimetric characteristics of the new GMS BT-125-1 125 I radioactive seed, including dose rate constant, radial dose functions, and anisotropy functions. METHODS: Dosimetric parameters of GMS BT-125-1 125 I seed including dose rate constant, radial dose functions, and anisotropy functions were calculated using the Monte Carlo code of MCNP5, and measured with thermoluminescent dosimeters (TLDs). The results were compared with those of PharmaSeed BT-125-1, PharmaSeed BT-125-2 125 I, and model 6711 125 I seeds. RESULTS: The dose rate constant of GMS BT-125-1 125 I seed was 0.959 cGy·h-1·U-1, with the difference of 0.94%, 0.83%, and 0.73% compared with the PharmaSeed BT-125-1 125 I seed, PharmaSeed BT-125-2 125 I seed, and Model 6711 125 I seed, respectively. For radial dose function, the differences between the Monte Carlo and the experimental g(r) results were mostly within 10%. Monte Carlo results of g(r) for GMS BT-125-1 125 I seed were found in agreement (within 3.3%) with corresponding results for the PharmaSeed BT-125-2 125 I seed. The largest differences were 8.1% and 6.2% compared with PharmaSeed BT-125-1 125 I seed and model 6711 125 I seed, respectively. For anisotropy function, the difference between GMS BT-125-1 125 I seed and PharmaSeed BT-125-2 125 I seed was typically <10%. CONCLUSIONS: The measured dose rate constant, radial dose functions, and two-dimensional anisotropy functions for the GMS BT-125-1 125 I seed showed good agreement with the Monte Carlo results. The dose rate constant of the GMS BT-125-1 125 I seed is similar to that of the PharmaSeed BT-125-1 125 I seed, the PharmaSeed BT-125-2 125 I seed, and the model 6711 125 I seed. For radial dose functions and two-dimensional anisotropy functions, the GMS BT-125-1 125 I seed is similar to the PharmaSeed BT-125-2 125 I seed but different from the PharmaSeed BT-125-1 125 I seed and the model 6711 125 I seed.

A method for confirming a third-party assay of I-125 seeds used for prostate implants.

The purpose of this work is to describe a method and apparatus that can be used to confirm the source strength of a large number of I-125 seeds while maintaining sterility, accuracy, reproducibility, and time efficiency. Source strengths ranging from 0.395 to 0.504 U/seed were available for this study. Three different seed configurations were measured: loose, linked, and loaded needles. A third-party 10% assay (NIST traceable) was provided. A custom stand was built out of aluminum to hold an exposure meter [Inovision (Fluke) 451P pressurized ion chamber] at 25 cm above the I-125 sources to measure the exposure rate. The measurements were made in an operating room, and a sterile sheet was placed under the nonsterile aluminum stand on a sterile loading table. Seeds and needles were placed in a sterile tray for these measurements. Two hundred and six loose seeds in six batches (0.395, 0.395, 0.409, 0.444, 0.444, and 0.444 U/seed) and 1434 seeds in 10 batches containing various strands (0.444, 0.444, 0.444, 0.444, .0444, 0.466, 0.466, 0.504, and 0.504 U/seed) were measured. For the loose and stranded seeds, the average exposure rate per unit activity was measured to be 0.589 mR/h·U with a standard deviation of 0.017. Loaded needles were measured with an average exposure rate per unit activity to be 0.269 mR/h·U with a standard deviation of 0.014. We conclude that the method described here is capable of confirming a third-party assay when performed on a large number of loose or stranded seeds in bulk. It is less reliable for preloaded needles.

Comparison of primary and secondary enucleation for uveal melanoma.

We investigated operative course and post-operative findings of patients undergoing primary enucleation for uveal melanoma versus those requiring secondary enucleation after brachytherapy. A retrospective chart review was performed with IRB approval on patients receiving treatment for uveal melanoma. Patients with enucleation as initial treatment and patients enucleated after plaque brachytherapy were analyzed for demographic data, operative course, and post-enucleation outcome. Further cause analysis for secondary enucleations was investigated. No significant difference was seen in age, laterality, or gender between the primarily enucleated (n = 54) and secondarily enucleated (n = 34) groups. Greater difficulty with surgery was noted in 28/32 (87.5%) of secondary enucleations compared to 1/54 (1.8%) of primary enucleations (p < 0.0001). Operative time was >2 hours in 3/51 (6%) of primary enucleations (vs. 8 of 32, 25%, p = 0.02). Average implant size was similar in the 2 groups (20.6 mm), however 2/34 (6%) of secondary enucleations required dermis fat grafting. Post-enucleation anophthalmic ptosis occurred after 8/49 (16%) of primary cases (vs. 13/30, 43%, p = 0.02) and prosthetic enophthalmos after none (0%) of primary cases (vs. 5/30, 17%, p = 0.006). Class 2 gene expression profile was found in 6/8 (60%) of eyes enucleated for treatment failure. Secondary enucleation performed after plaque brachytherapy was technically more difficult, and had more anophthalmic socket and eyelid complications compared to primary enucleation for uveal melanoma. Primary enucleation may avoid additional surgery and morbidity in a subset of patients with contraindications to plaque brachytherapy.

[Low dose-rate contact radiation therapy (brachytherapy) for prostate cancer using domestic I-125 seeds as a monotherapy and combined with pelvic lymphadenectomy].

INTRODUCTION: In 2014, the incidence of prostate cancer in the Russian Federation was 116.4 per 100,000 population. It is noteworthy that from 2004 to 2014, the proportion of patients with stage I-II prostate cancer increased from 35.5% to 52.5%, while that of patients with stages III and IV disease decreased from 38.4% to 29% and from 22.7% to 16.5%, respectively. All of this allows an increasing number of prostate cancer patients to be treated with radical treatment - low dose-rate brachytherapy. For the first time in this country, we report a clinical trial of low dose-rate brachytherapy for prostate cancer using domestically manufactured I-125 seeds. The successful results of this clinical trial are presented in this article. The aim of this work was to show the clinical efficacy and safety of domestically manufactured I-125 seeds for low dose-rate prostate cancer brachytherapy. MATERIALS AND METHODS: The clinical trial comprised 36 patients with stage T1-T2 prostate cancer. Patients were randomly assigned according to the risk of cancer progression. Low and intermediate risk groups comprised 30 (83.3%) and 6 (16.7%) patients, respectively. Patients of low risk group underwent brachytherapy alone with the minimum therapeutic dose of 145 Gy. I-125 seeds of two activities, 0.55 and 0.35 mCi per seed were used for implantation. Depending on the prostate volume, from 40 to 80 seeds, 57 on average were implanted. Mean implantation time was 85 minutes. In patients of the intermediate risk group brachytherapy was performed in combination with laparoscopic pelvic lymphadenectomy which was carried out 4-5 weeks prior to brachytherapy. RESULTS: Follow-up examination at 6 months after implantation showed that PSA decreased in all patients on average by 87% from the baseline. No adverse events were reported. CONCLUSION: The findings of the clinical trials of domestically manufactured I-125 seeds showed they are effective, safe and comply with international standards.

Synthesis and preliminary characterization of radioiodinated benzofuran-3-yl-(indol-3-yl)maleimide derivatives as potential SPECT imaging probes for the detection of glycogen synthase kinase-3ß (GSK-3ß) in the brain.

We report on the synthesis and preliminary characterization of two radioiodinated benzofuran-3-yl-(indol-3-yl)maleimides, 3-(benzofuran-3-yl)-4-(5-[(125) I]iodo-1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione ([(125) I]5), and 3-(5-[(125) I]iodo-1-methyl-1H-indol-3-yl)-4-(6-methoxybenzofuran-3-yl)-1H-pyrrole-2,5-dione ([(125) I]6), as the first potential SPECT imaging probes targeting glycogen synthase kinase-3ß (GSK-3ß). In this study, we used (125) I as a surrogate of (123) I because of its ease of use. The radioiodinated ligands were prepared from the corresponding tributyltin precursors through an iododestannylation reaction using hydrogen peroxide as an oxidant with a radiochemical yield of 10-30%. In vitro binding experiments suggested that both compounds show high affinity for GSK-3ß at a level similar to a known GSK-3ß inhibitor. Biodistribution studies with normal mice revealed that the radioiodinated compounds display sufficient uptake into (1.8%ID/g at 10 min postinjection) and clearance from the brain (1.0%ID/g at 60 min postinjection). These preliminary results suggest that the further optimization of radioiodinated benzofuran-3-yl-(indol-3-yl)maleimide derivatives may facilitate the development of clinically useful SPECT imaging probes for the in vivo detection of GSK-3ß.

Brachytherapy in the treatment of recurrent aggressive falcine meningiomas.

Recurrent aggressive falcine meningiomas are uncommon tumors that recur despite receiving extensive surgery and radiation therapy (RT). We have utilized brachytherapy as a salvage treatment in two such patients with a unique implantation technique. Both patients had recurrence of WHO Grade II falcine meningiomas despite multiple prior surgical and RT treatments. Radioactive I-125 seeds were made into strands and sutured into a mesh implant, with 1 cm spacing, in a size appropriate to cover the cavity and region of susceptible falcine dura. Following resection the vicryl mesh was implanted and fixed to the margins of the falx. Implantation in this interhemispheric space provides good dose conformality with targeting of at-risk tissue and minimal radiation exposure to normal neural tissues. The patients are recurrence free 31 and 10 months after brachytherapy treatment. Brachytherapy was an effective salvage treatment for the recurrent aggressive falcine meningiomas in our two patients.

A hybrid solid-fluorous phase radioiodination and purification platform.

A new class of fluorous materials was developed to create a hybrid solid-solution phase strategy for the expedient preparation and HPLC-free purification of (125) I-labeled compounds. The system is referred to as a hybrid platform in that it combines solution phase labeling and fluorous solid-phase purification in one step as opposed to two separate individual processes. Treatment of fluorous arylstannanes coated on fluorous silica with [(125) I]NaI and the appropriate oxidant made it possible to produce and selectively isolate the nonfluorous radiolabeled products in high purity (>98%) free from excess starting material and unreacted radioiodine. Examples included simple aryl and heterocyclic (click) derivatives, known radiopharmaceuticals including meta-iodobenzylguanidine (MIBG) and iododeoxyuridine (IUdR), and a new agent with high affinity for prostate-specific membrane antigen. The coated fluorous silica kits are simple to prepare, and reactions can be performed at room temperature using different oxidants generating products in minutes in biocompatible solutions.

Outcomes of I-125 Low-Dose-Rate Brachytherapy in Patients with Localized Prostate Cancer: A Comprehensive Analysis from a Specialized Tertiary Referral Center.

Low-dose-rate (LDR) brachytherapy with I-125 seeds is one of the most common primary tumor treatments for low-risk and low-intermediate-risk prostate cancer. This report aimed to present an analysis of single-institution long-term results. We analyzed the treatment outcomes of 119 patients with low- and intermediate-risk prostate cancer treated with LDR brachytherapy at our institution between 2014 and 2020. The analysis focused on biochemical recurrence rates (BRFS), overall survival (OS), cumulative local recurrence rate (CLRR), and the incidence of acute and late toxicities. Patient-reported quality of life measures were also evaluated to provide a holistic view on the treatment's impact. The median follow-up period was 46 months. CLRR was 3.3% (4/119), five-year BRFS was 87%, and the five-year OS rate was 95%. Dysuria was the most common acute urinary toxicity, reported in 26.0% of patients as grade 1 and 13.4% as grade 2. As a late side effect, 12.6% of patients experienced mild dysuria. Sexual dysfunction persisted in 6.7% of patients as grade 1, 7.5% as grade 2, and 10.0% as grade 3. LDR brachytherapy in patients with prostate cancer is an effective treatment, with favorable clinical outcomes and manageable toxicity. The low CLRR and high OS rates, as well as low incidence of severe side effects, support the continued use of LDR brachytherapy as a primary treatment modality for localized prostate cancer.

Iodine-125 brachytherapy suppresses tumor growth and alters bone metabolism in a H1299 xenograft mouse model.

The present study aimed to investigate the efficacy of Iodine-125 (I-125) brachytherapy in a mouse model of non-small cell lung cancer, to further explore the efficacy and appropriate method of implantation of the I-125 radioactive seed. This study also aimed to determine the impact of brachytherapy on bone metabolism. A total of 18 mice were used to establish H1299 xenograft models, and were randomly assigned to three groups. These included non-radioactive seed implantation (Sham IM), fractionated I-125 seed implantation (Fractionated IM) and single I-125 seed implantation (Single IM) groups. Mice were euthanized after 28 days of implantation. H&E staining, Ki67 immunohistochemistry, CD31 morphometric analysis and TUNEL immunofluorescence assays were respectively used to determine the histopathological changes, proliferation, micro-angiogenesis and apoptosis of tumors. In addition, bone volume and microstructure were evaluated using trabecular bone area (Tb.Ar), trabecular thickness (Tb.Th), trabecular number (Tb.N) and cortical thickness. Bone metabolic status was analyzed using histomorphometric staining of tartrate-resistant acid phosphate (TRAP) and alkaline phosphatase (ALP) expression in the femur, and using an ELISA assay to determine the expression of C-telopeptide of type 1 collagen (CTX-1) and procollagen type 1 n-terminal propeptide (P1NP) in the serum. Moreover, reverse transcription-quantitative PCR and western blotting were carried out for the analysis of bone remodeling-related gene expression in the bone tissue. Results of the present study demonstrated that compared with the Sham IM group, both the I-125 seed implantation groups, including Fractionated IM and Single IM, demonstrated significant therapeutic effects in both tumor volume and weight. More specifically, the most significant therapeutic effects on tumor inhibition were observed in the Fractionated IM group. Results of Ki67 and CD31 immunohistochemical staining suggested a notable reduction in tumor cell proliferation and micro-angiogenesis, and results of the TUNEL assay demonstrated an increase in tumor cell apoptosis. Although the cortical bone appeared thinner and more fragile in both I-125 seed implantation groups, no notable adverse changes in the morphology of the cancellous bone were observed, and the index of Tb.Ar, Tb.Th and Tb.n was not significantly different among Sham IM and I-125 implantation groups. However, alterations in bone metabolism were characterized by a decrease in CTX-1 and P1NP expression, accompanied by an increase in TRAP activity and a decrease in ALP activity. Results of the present study also demonstrated the notable suppression of osteocalcin and runt-related transcription factor 2. I-125 seed implantation may be an effective and safe antitumor strategy. Moreover, the use of fractionated implantation patterns based on tumor shape exhibited improved therapeutic effect on tumor suppression when the total number of I-125 seeds was equivalent along with reduced complications associated with bone loss.

Outcomes after PD-103 versus I-125 for low dose rate prostate brachytherapy monotherapy: An international, multi-institutional study.

BACKGROUND AND PURPOSE: Pd-103 and I-125 are commonly used in low dose rate (LDR) brachytherapy for prostate cancer. Comparisons of outcomes by isotope type are limited, but Pd-103 has distinct radiobiologic advantages over I-125 despite its lesser availability outside the United States. We evaluated oncologic outcomes after Pd-103 vs I-125 LDR monotherapy for prostate cancer. MATERIALS AND METHODS: We retrospectively analyzed databases at 8 institutions for men who received definitive LDR monotherapy with Pd-103 (n = 1,597) or I-125 (n = 7,504) for prostate cancer. Freedom from clinical failure (FFCF) and freedom from biochemical failure (FFBF) stratified by isotope were analyzed by Kaplan-Meier univariate and Cox multivariate analyses. Biochemical cure rates (prostate-specific antigen level ≤ 0.2 ng/mL between 3.5 and 4.5 years of follow-up) by isotype were calculated for men with at least 3.5 years of follow-up and compared by univariate and multivariate logistic regression. RESULTS: Compared with I-125, Pd-103 led to higher 7-year rates of FFBF (96.2% vs 87.6%, P < 0.001) and FFCF (96.5% vs 94.3%, P < 0.001). This difference held after multivariate adjustment for baseline factors (FFBF hazard ratio [HR] = 0.31, FFCF HR = 0.49, both P < 0.001). Pd-103 was also associated with higher cure rates on univariate (odds ratio [OR] = 5.9, P < 0.001) and multivariate (OR = 6.0, P < 0.001) analyses. Results retained significance in sensitivity analyses of data from the 4 institutions that used both isotopes (n = 2,971). CONCLUSIONS: Pd-103 monotherapy was associated with higher FFBF, FFCF, and biochemical cure rates, and suggests that Pd-103 LDR may lead to improved oncologic outcomes compared with I-125.

Giant calcifying epithelial odontogenic tumor after I-125 seed implantation: A case report.

Calcifying Epithelial Odontogenic Tumor (CEOT), also known as Pindborg tumor, is a rare odontogenic benign tumor. It was first reported by Thoma and Goldman in 1946 and defined as an independent tumor by Pindborg in 1957. Herein, we reported a CEOT case involving most of the mandible after I-125 implantation in a 53-year-old man. We cooperated with governmental and hospital departments to resect the tumors, reconstruct the mandible with a fibular flap graft, and properly dispose of the radioactive particles.