Vía clínica de terapia metabólica con 131I en cáncer diferenciado de tiroides / Clinical pathway of metabolic therapy with 131I in differentiated thyroid cancer

Las vías clínicas son planes asistenciales que se aplican a procesos clínicos de curso predecible con la intención de protocolizarlos y disminuir la variabilidad en su manejo. Nuestro objetivo ha sido desarrollar una vía clínica para la terapia metabólica con 131I, proceso asistencial aplicado a los pacientes con carcinoma diferenciado de tiroides. Se organizó un equipo de trabajo formado por médicos (endocrinología y medicina nuclear), personal de enfermería (unidad de hospitalización y medicina nuclear), de radiofísica y del servicio de apoyo a la gestión clínica y continuidad asistencial. Para el diseño de la vía clínica se realizaron varias reuniones del equipo, en las que se pusieron en común las revisiones bibliográficas y se abordó el diseño y el desarrollo de la vía, respetando las guías clínicas vigentes. Este equipo ha logrado mediante consenso la elaboración del plan asistencial, estableciendo sus puntos clave y redactando los distintos documentos que componen la vía clínica: matriz temporal, documento de registro de variaciones de la vía clínica, documentos de información al paciente, encuesta de satisfacción del paciente, folleto de pictogramas, indicadores de evaluación de calidad. Por último, la vía clínica se ha presentado a todos los servicios clínicos involucrados y a la dirección médica del hospital, procediendo a su implementación en la práctica clínica (AU)

Clinical pathways are care plans that are applied to clinical processes with a predictable course, with the intention of protocolizing them, and reducing the variability in their management. Our objective was to develop a clinical pathway for 131I metabolic therapy, in its application to differentiated thyroid cancer. A work team was organised consisting of doctors (Endocrinology and Nuclear Medicine), nursing staff (Hospitalisation Unit and Nuclear Medicine), Radiophysics and the Clinical Management and Continuity of Care Support Service. For the design of the clinical pathway, several team meetings were held, in which the literature reviews were pooled and the design and development of the clinical pathway was undertook, in accordance with current clinical guidelines. This team has achieved consensus on the development of the care plan, establishing its key points and drafting the different documents that make up the clinical pathway: timeframe-based schedule, clinical pathway variation record document, patient information documents, patient satisfaction survey, pictogram brochure, quality assessment indicators. Finally, the clinical pathway was presented to all clinical departments involved and to the medical director of the hospital, and it is now being implemented in clinical practice (AU)

Extracellular vesicles deliver sodium iodide symporter protein and promote cancer cell radioiodine therapy.

Extracellular vesicles (EVs) are a promising carrier for various cargos with antitumor effects, but their capacity to transfer the ability to transport radioiodine for cancer theranostics remains unexplored. Herein, we tested the hypothesis that EVs can be loaded with the sodium iodide symporter (NIS) protein and efficiently deliver the payload to recipient cancer cells to facilitate radioiodine uptake. The results revealed that donor cells either transduced with an adenoviral vector for transient expression or engineered for stable overexpression secreted EVs that contained substantial amounts of NIS protein but not NIS mRNA. Huh7 liver cancer cells treated with EVs secreted from each of the donor cell types showed significantly increased plasma membrane NIS protein, indicating efficient payload delivery. Furthermore, intact function of the delivered NIS protein was confirmed by significantly increased radioiodine transport in recipient cancer cells that peaked at 48 h. Importantly, NIS protein delivered by EVs significantly enhanced the antitumor effects of 131I radiotherapy. These results reveal that EVs are a promising vehicle to deliver NIS protein to cancer cells in sufficient amounts for radioiodine-based theranostics.

Cirugía radioguiada con semillas de yodo-125 en pacientes con cáncer de mama tratadas con quimioterapia neoadyuvante / Radioguided surgery with iodine-125 seeds in breast cancer patients treated with neoadjuvant chemotherapy

Objetivo: Evaluar la utilización de las semillas radiactivas de yodo-125 (SRI-125) en la cirugía de mama o axila, en pacientes con cáncer de mama tratadas con quimioterapia neoadyuvante (QtNeo).Material y métodos: Estudio prospectivo, entre enero del 2016 y junio del 2020; 80 mujeres T1-3, N0-2, M0: 30 marcaje SRI-125 del tumor en mama, 36 tanto del tumor como del ganglio axilar positivo biopsiado, y 14 solo de axila. Edad: 54,7±11,4 años. Tamaño tumoral: 34,1±14,6mm. Tipo histológico: ductal infiltrante 90,0%. Subtipos moleculares: luminal-A 23,8%; luminal-B/HER2- 33,7%; luminal-B/HER2+ 18,8%; HER2+ 7,5%; triple negativo 16,2%.Resultados: De las 66 pacientes con marcaje SRI-125 del tumor (51 pre-QtNeo, 15 post-QtNeo), el 92,1% presentaba márgenes quirúrgicos libres, con un volumen de las piezas de 126,7±111,2 cm3. De las 5 reintervenciones, en 3 la ampliación fue positiva (una mastectomía).De las 50 pacientes N1 con marcaje SRI-125 (GM), 44 pre-QtNeo y 6 post-QtNeo, se identificó el GM en el 97,2%: negativo en 23, positivo en 26. En 45 se realizó biopsia selectiva del ganglio centinela y se identificó en el 93,3%: negativo en 26, positivo en 16. En un caso la SRI-125 no se colocó correctamente y tampoco se localizó GC por no migración.En el 61,9% de las pacientes el GM se encontraba entre el/los GC identificados en la cirugía. En 5 pacientes, con GC y GM no coincidentes, el resultado anatomopatológico del GC fue negativo y el GM positivo. En 53,8% de las pacientes se realizó linfadenectomía axilar. Conclusión: Las SRI-125 permiten realizar cirugía conservadora de la mama y mejorar la detección de enfermedad residual axilar, en pacientes tratadas con QtNeo (AU)

Objective: To evaluate the use of radioactive iodine-125 seed (RIS) in breast and/or axillary surgery, in patients with breast cancer treated with neoadjuvant chemotherapy (NAC).Material and methods: Prospective study between January 2016 and June 2020. 80 women T1-3,N0-2,M0: 30 RIS marking the breast tumor, 36 both the tumor and the biopsied positive axillary node, and 14 only the axilla. Age: 54.7±11.4 years. Tumor size: 34.1±14.6mm. Histological type: invasive ductal carcinoma 90.0%. Molecular subtypes: luminal-A 23.8%, luminal-B/HER2- 33.7%, luminal-B/HER2+ 18.8%, HER2+ 7.5%, basal-like 16,2%.Results: Of the 66 patients with RIS marking of the tumor (51 pre-NAC, 15 post-NAC), 92.1% had tumor-free surgical margins, with a specimen volume of 126.7±111.2 cm3. Of the 5 second local excisions, in 3 the resection margin was involved (1 mastectomy).Of the 50 patients N1 with RIS marking (MLN), 44 pre-NAC and 6 post-NAC, MLN was identified in 97.2%: negative 23, positive 26. In 45/50 patients, sentinel node biopsy (SNB) was performed and it was identified in 93.3%: negative 26, positive 16. In 1 case RIS was not placed correctly and SNB was not identified due to non-migration.In 61.9% of the patients, MLN was among the SNB identified in the surgery. In 5 patients with mismatched SNB and MLN, the pathological result of the SNB was negative and the MLN was positive. Axillary lymph node dissection was performed in 53.8% of the patients.Conclusion: RIS allow to perform breast-conserving surgery and improve detection of residual axillary disease in patients treated with NAC (AU)

Effects of I125 seed stent implantation combined with arterial infusion chemoembolization on tumor markers, p53 expression, and prognosis in patients with cholangiocarcinoma.

Cholangiocarcinoma is a common malignant tumor. Advanced treatment is difficult and the prognosis is poor. It is of great significance to find an effective method to treat cholangiocarcinoma and improve the prognosis of patients. Therefore, 78 patients with cholangiocarcinoma treated in our hospital were divided into group A and group B according to different treatment methods. The clinical effect, bilirubin, tumor size, bile duct patency time, tumor marker level To evaluate the therapeutic effect of I125 seed stent implantation combined with arterial infusion chemoembolization in patients with cholangiocarcinoma. The results showed that I125 seed stent implantation combined with TACE in the treatment of patients with cholangiocarcinoma can play an obvious clinical effect, effectively reduce the level of tumor markers and p53, reduce tumor lesions, improve the survival rate of patients, and play an important role in tumor treatment.

(cRGD)2 peptides modified nanoparticles increase tumor-targeting therapeutic effects by co-delivery of albendazole and iodine-131.

Albendazole (ABZ), a clinical antiparasitic drug, has shown potential antitumor effects in various tumors. Herein, we prepared dimeric cRGD [(cRGD)2] modified human serum albumin (HSA) nanosystem to co-delivery of albendazole (ABZ) and iodine-131 (131I) for chemoradiotherapy of triple-negative breast cancer (TNBC). HSA@ABZ NPs were synthesized by the self-assembly method. 131I-(cRGD)2/HSA@ABZ NPs were fabricated through covalently binding HSA@ABZ NPs with (cRGD)2 peptides, followed by chloramine T direct labeling with 131I. In vitro therapeutic effects on TNBC (MDA-MB-231 and 4T1 cells) were determined using MTT assay, crystal violet assay, wound-healing assay and western blotting analysis. In vivo treatment was performed using 4T1-bearing mice, and the tumor-targeting efficacy was assessed by gamma imaging. The distribution of NPs was quantitatively analyzed by detecting the gamma counts in tumor and main organs. The nanoparticles possessed negative charge, moderate size and good polydispersity index. Dual responding to pH and redox, the in vitro release rate of ABZ was more than 80% in 72 h. In vitro, NPs inhibited the proliferation of TNBC cells in a concentration-dependent manner and decreased cell migration. Western blotting analysis showed that the NPs, as well as free ABZ, cell-dependently induced autophagy and apoptosis by restraining or promoting the expression of p-p38 and p-JNK MAPK. In vivo, gamma imaging exhibited an earlier and denser radioactivity accumulation in tumor of 131I-(cRGD)2/HSA@ABZ NPs compared to NPs free of (cRGD)2 conjugating. Furthermore, 131I-(cRGD)2/HSA@ABZ NPs significantly suppressed tumor growth by restraining proliferation and promoting apoptosis in vivo. Our study suggested that the nanoparticles we developed enhanced tumor-targeting of ABZ and increased antitumor effects by combination of chemotherapy and radiotherapy.

Insurance type is associated with appropriate use of surgical and adjuvant care for differentiated thyroid carcinoma.

BACKGROUND: We aimed to characterize the association between differentiated thyroid cancer (DTC) patient insurance status and appropriateness of therapy (AOT) regarding extent of thyroidectomy and radioactive iodine (RAI) treatment. METHODS: The National Cancer Database was queried for DTC patients diagnosed between 2010 and 2016. Adjusted odds ratios (AOR) for AOT, as defined by the American Thyroid Association guidelines, and hazard ratios (HR) for overall survival (OS) were calculated. A difference-in-differences (DD) analysis examined the association of Medicaid expansion with outcomes for low-income patients aged <65. RESULTS: A total of 224,500 patients were included. Medicaid and uninsured patients were at increased risk of undergoing inappropriate therapy, including inappropriate lobectomy (Medicaid 1.36, 95% confidence interval [CI]: 1.21-1.54; uninsured 1.30, 95% CI: 1.05-1.60), and under-treatment with RAI (Medicaid 1.20, 95% CI: 1.14-1.26; uninsured 1.44, 95% CI: 1.33-1.55). Inappropriate lobectomy (HR 2.0, 95% CI: 1.7-2.3, P < .001) and under-treatment with RAI (HR 2.3, 95% CI: 2.2-2.5, P < .001) were independently associated with decreased survival, while appropriate surgical resection (HR 0.3, 95% CI: 0.3-0.3, P < .001) was associated with improved odds of survival; the model controlled for all relevant clinico-pathologic variables. No difference in AOT was observed in Medicaid expansion versus non-expansion states with respect to surgery or adjuvant RAI therapy. CONCLUSION: Medicaid and uninsured patients are at significantly increased odds of receiving inappropriate treatment for DTC; both groups are at a survival disadvantage compared with Medicare and those privately insured.

Low-Iodine Diet of 4 Days Is Sufficient Preparation for 131I Therapy in Differentiated Thyroid Cancer Patients.

CONTEXT: No consensus exists about the optimal duration of the low-iodine diet (LID) in the preparation of 131I therapy in differentiated thyroid cancer (DTC) patients. OBJECTIVE: This work aimed to investigate if a LID of 4 days is enough to achieve adequate iodine depletion in preparation for 131I therapy. In addition, the nutritional status of the LID was evaluated. METHODS: In this prospective study, 65 DTC patients treated at 2 university medical centers were included between 2018 and 2021. The patients collected 24-hour urine on days 4 and 7 of the LID and kept a food diary before and during the LID. The primary outcome was the difference between the 24-hour urinary iodine excretion (UIE) on both days. RESULTS: The median 24-hour UIE on days 4 and 7 of the LID were not significantly different (36.1 mcg [interquartile range, 25.4-51.2 mcg] and 36.5 mcg [interquartile range, 23.9-47.7 mcg], respectively, P = .43). On day 4 of the LID, 72.1% of the DTC patients were adequately prepared (24-hour UIE < 50 mcg), and 82.0% of the DTC patients on day 7 (P = .18). Compared to the self-reported regular diet, DTC patients showed a significantly (P < .01) lower percentage of nutrient intake (calories, protein, calcium, iodine, and water) during the LID. CONCLUSION: The 24-hour UIE on day 4 of the LID did not differ from day 7, and therefore shortening the LID from 7 to 4 days seems justified to prepare DTC patients for 131I therapy in areas with sufficient iodine intake and may be beneficial to maintain a sufficient nutritional intake during DTC treatment.

Extraction, purification and radioiodination of Khellin as cancer theranostic agent.

Khellin was successfully extracted from Ammi visnaga fruits with a recovery percent of 96.15%. Next radio-iodination of Khellin was successfully achieved with a high yield. The biodistribution study of [131I]iodo-khellin in tumour bearing mice revealed that khellin preferentially localization at tumour tissue. Target prediction study for [131I]iodo-khellin revealed that PI3K and VEGFR are potential targets for iodo-khellin with good affinity. The results of this study potentiate [131I]iodo-khellin as a good theranostic agent for tumour imaging and therapy.

Isolated poorly differentiated cancer (insular) in a thyroglossal cyst: a case report.

A 23-year-old young man presented with a painless neck mass that he noticed slowly growing over the past 4 years. Neck imaging showed an irregular 5 x 5 cm mixed solid and cystic mass in mid neck that looked suspicious but normal looking thyroid and no neck lymphadenopathy. Thyroid uptake scan was within normal also. Fine needle biopsy (FNA) from thyroglossal cyst (TGC) was malignant, Bethesda VI. Multi-disciplinary meeting discussed the case and advised for removal of both the TGC cancer and total thyroidectomy. After patient counseling, he underwent Sistrunk procedure for excision of the TGC mass and total thyroidectomy. histopathological examination revealed a poorly differentiated carcinoma of insular type in TGC with unremarkable thyroid gland. Patient recovery was uneventful. Post-operative multi-disciplinary meeting discussed the histopathology results and advised for post-operative radioactive iodine therapy (RAI) and thyroxine suppression followed by serum thyroid stimulating hormone (TSH) and thyroglobulin (TG). We shall review the diagnostic and management considerations of our case having this rare cancer.

Effect of TSH stimulation protocols on adequacy of low-iodine diet for radioiodine administration.

Low-iodine diet (LID) is a crucial preparation for radioactive iodine (RAI) treatment or scan in thyroid cancer. The aim of this study is to analyze the influence of thyroid stimulating hormone (TSH) stimulation protocols and other clinical factors on LID adequacy. Thyroid cancer patients who underwent LID for RAI scan or treatment were retrospectively analyzed. Patients were guided to have LID for 2 weeks before RAI administration and urine iodine/creatinine ratio (UICR, µg/g Cr) was measured. TSH stimulation was conducted using either thyroid hormone withdrawal (THW) or recombinant human TSH (rhTSH) injection. Adequacy of LID was classified by UICR as 'excellent (< 50)', 'adequate (50-100)', 'inadequate (101-250)' and 'poor (> 250)'. A total of 1715 UICR measurements from 1054 patients were analyzed. UICR was significantly higher in case of rhTSH use than THW (72.4 ± 48.1 vs. 29.9 ± 45.8 µg/g Cr, P < 0.001). In patients who underwent LID twice using both TSH stimulation protocols alternately, UICR was higher in case of rhTSH than THW regardless of the order of method. Among clinical factors, female, old-age, and the first LID were significant factors to show higher UICR. Although the adequacy of LID was 'adequate' or 'excellent' in most patients, multivariate analysis demonstrated that THW method, male, young age, and prior LID-experience were significant determinants for achieving 'excellent' adequacy of LID. In conclusion, UICR was higher and the proportion of 'excellent' LID adequacy was lower with rhTSH than with THW. UICR was higher also in women, old-age, and LID-naïve patients. Further researches are required to suggest effective methods to reduce body iodine pool in case of rhTSH use and to validate the efficacy of such methods on outcomes of RAI treatment.

Usefulness of 123I-BMIPP and 201TlCl nuclide scintigraphy in evaluation of myocarditis in patients with polymyositis or dermatomyositis.

ABSTRACT: To investigate the usefulness of 123I-BMIPP/201TlCl scintigraphy for evaluating the presence of myocarditis in patients with polymyositis (PM) or dermatomyositis (DM).We performed a retrospective study of 26 patients diagnosed with new-onset active PM/DM who underwent 123I-BMIPP/201TlCl scintigraphy between 01 April 2010 and 20 March 2015. We determined the 123I-BMIPP/201TlCl ratio and grouped the patients according to presence or absence of a mismatch. We evaluated the relationship between mismatch and the laboratory and echocardiographic findings.Mismatch was found in 13 (50%) patients. There was no statistically significant difference in age, cardiac troponin T, myoglobin, myosin light chain, aldolase levels, E wave/A wave ratio, right ventricular systolic pressure between the mismatch and non-mismatch groups. Left ventricular end-diastolic and end-systolic dimensions were significantly greater in the mismatch group (45.0 vs 42.5 mm, P =  < .01 and 29.5 mm vs 25.0 mm, P < .01). Left ventricular ejection fraction was significantly lower in the mismatch group (63.5% vs 71.5%, P = .04). Significant inverse correlation (r = -0.44, P = .03) was observed between left ventricular ejection fraction and mismatch ratio.The use of 123I-BMIPP/ 201TlCl scintigraphy may be considered for evaluating myocarditis in patients with PM/DM.

Long-term male fertility after treatment with radioactive iodine for differentiated thyroid carcinoma.

CONTEXT: Whilst radioactive iodine (RAI) is often administered in the treatment for differentiated thyroid carcinoma (DTC), long-term data on male fertility after RAI are scarce. OBJECTIVE: To evaluate long-term male fertility after RAI for DTC, and to compare semen quality before and after RAI. DESIGN, SETTING, AND PATIENTS: Multicenter study including males with DTC ≥2 years after their final RAI treatment with a cumulative activity of ≥3.7 GBq. MAIN OUTCOME MEASURE(S): Semen analysis, hormonal evaluation, and a fertility-focused questionnaire. Cut-off scores for 'low semen quality' were based on reference values of the general population as defined by the World Health Organization (WHO). RESULTS: Fifty-one participants had a median age of 40.5 (interquartile range (IQR): 34.0-49.6) years upon evaluation and a median follow-up of 5.8 (IQR: 3.0-9.5) years after their last RAI administration. The median cumulative administered activity of RAI was 7.4 (range: 3.7-23.3) GBq. The proportion of males with a low semen volume, concentration, progressive motility, or total motile sperm count did not differ from the 10th percentile cut-off of a general population (P = 0.500, P = 0.131, P = 0.094, and P = 0.500, respectively). Cryopreserved semen was used by 1 participant of the 20 who had preserved semen. CONCLUSIONS: Participants had a normal long-term semen quality. The proportion of participants with low semen quality parameters scoring below the 10th percentile did not differ from the general population. Cryopreservation of semen of males with DTC is not crucial for conceiving a child after RAI administration but may be considered in individual cases.

Analysis on the accuracy of CT-guided radioactive I-125 seed implantation with 3D printing template assistance in the treatment of thoracic malignant tumors.

This article analyzes the accuracy of needle track and dose of a 3-dimensional printing template (3DPT) in the treatment of thoracic tumor with radioactive I-125 seed implantation (RISI). A total of 28 patients were included. The technical process included: (i) preoperative CT positioning, (ii) preoperative planning design, (iii) 3DPT design and printing, (iv) 3DPT alignment, (v) puncture and seed implantation. The errors of needle position and dosimetric parameters were analyzed. A total of 318 needles were used. The mean errors in needle depth, needle insertion point, needle tip and needle angle were 0.52 ± 0.48 cm, 3.4 ± 1.7 mm, 4.4 ± 2.9 mm and 2.8 ± 1.7°, respectively. The differences between actual needle insertion angle and needle depth and those designed in the preoperative were statistically significant (p < 0.05). The mean values of all the errors of the chest wall cases were smaller than those of the lungs, and the differences were statistically significant (p < 0.05). There was no significant difference between the D90 calculated in the postoperative plan and those designed in the preoperative and intraoperative plans (p > 0.05). Some dosimetric parameters of preoperative plans such as V100, V200, CI and HI were not consistent with that of preoperative plans, and the difference was statistically significant (p < 0.05). However, there were no statistical difference in the dosimetric parameters between the postoperative plans and intraoperative plans (p > 0.05). We conclude that for thoracic tumors, even under the guidance of 3DPT, there will be errors. The plan should be optimized in real time during the operation.

Occupational exposure and radiobiological risk from thyroid radioiodine therapy in Saudi Arabia.

Worldwide, thyroid cancer accounts for some 10% of total cancer incidence, most markedly for females. Thyroid cancer radiotherapy, typically using 131I (T1/2 8.02 days; ß- max energy 606 keV, branching ratio 89.9%), is widely adopted as an adjunct to surgery or to treat inoperable cancer and hyperthyroidism. With staff potentially receiving significant doses during source preparation and administration, radiation protection and safety assessment are required in ensuring practice complies with international guidelines. The present study, concerning a total of 206 patient radioiodine therapies carried out at King Faisal Specialist Hospital and Research Center over a 6-month period, seeks to evaluate patient and occupational exposures during hospitalization, measuring ambient doses and estimating radiation risk. Using calibrated survey meters, patient exposure dose-rate estimates were obtained at a distance of 30-, 100- and 300 cm from the neck region of each patient. Occupational and ambient doses were measured using calibrated thermoluminescent dosimeters. The mean and range of administered activity (AA, in MBq) for the thyroid cancer and hyperthyroidism treatment groups were 4244 ± 2021 (1669-8066), 1507.9 ± 324.1 (977.9-1836.9), respectively. The mean annual occupational doses were 1.2 mSv, that for ambient doses outside of the isolation room corridors were found to be 0.2 mSv, while ambient doses at the nursing station were below the lower limit of detection. Exposures to staff from patients being treated for thyroid cancer were less compared to hyperthyroidism patients. With a well-defined protocol, also complying with international safety requirements, occupational exposures were found to be relatively high, greater than most reported in previous studies.

Comparison of three-dimensional-printed template-guided and traditional implantation of 125I seeds for gynecological tumors: A dosimetric and efficacy study.

OBJECTIVE: The objective of the study was to compare the dose parameter and clinical efficacy of three-dimensional-printed template (3D-PT)-guided and traditional 125I seed implantation in treatment of gynecological tumors. MATERIALS AND METHODS: A total of 28 patients with gynecological tumors treated with radioactive seed implantation in Hebei General Hospital from January 2016 to December 2018 were retrospectively analyzed. Twelve patients (template group) were guided by 3D-PT and the remaining 16 patients (traditional group) were guided by computed tomography (CT) with traditional technique. Preoperative treatment plan (preplan) was completed through a treatment planning system. In the template group, 3D-PT was printed according to preplan and seeds were implanted under the guidance of 3D-PT and CT. In the traditional group, seeds were implanted under the guidance of single CT directly according to the preplan. Postoperative verification plan (post-plan) was completed. Dose-volume histogram (DVH) was calculated and D80, D90, V90, V100, and V150 were obtained according to DVH. Then, deviation of the dosimetric parameters D80, D90, V90, V100, and V150 between the preplan and postplan were compared within the two groups. The difference and percentage of difference of the above dosimetric parameters between the preplan and postplan within the two groups were calculated using the formula Xd = Xpost-plan- Xpre-plan, and Xd% = (Xpost-plan- Xpre-plan)/Xpre-plan × 100%. Doses were calculated to determine whether the differences there were statistically significant. Efficacy evaluation was completed according to RECISIT 1.1. Local control rate and effective rate of 2-months postplan were compared between the two groups. Survival analysis was completed by the Kaplan-Meier method. The patients were followed up for 12 months, and their survival rate was calculated and compared. RESULTS: There was no significant difference between the two groups for all the parameters, except for D80 of the preplan and postplan in the traditional group (P = 0.000). All the differences and percentage of difference were calculated and it was found that the Xd difference of D80 (P = 0.035), D90 (P = 0.023), V90 (P = 0.047), V100 (P = 0.032), and V150 (P = 0.031), as well as the Xd% difference of D80 (P = 0.032), D90 (P = 0.034), V90 (P = 0.042), V100 (P = 0.036), and V150 (P = 0.044) of the two groups was statistically significant, thus indicating that the dosimetric parameter fluctuation in the template group was more stable. The result of the curative effect after 2 months were as follows: the local control rate and effective rate of the template group were 100% (12/12) and 83.3% (10/12), while those of the traditional group were 100% (16/16) and 81.2% (13/16). There was no statistically significant difference in the curative effect between the two groups. After 6-27 months (median = 12 months) of follow-up, the median survival time of the template group and traditional group were 17 (10-23) and 16 (11-20) months, respectively, and the 1-year overall survival rate was 63% and 79% (P = 0.111), respectively, with no statistically significant difference observed. CONCLUSION: 3D-PT-guided 125I seed implantation is safe and effective in the treatment of gynecological tumors.

The clinical efficacy of computed tomography-guided 125I particle implantation combined with arterial infusion chemotherapy in the treatment of pancreatic cancer.

AIMS: This study aimed to investigate the clinical value of 125I radioactive particle implantation combined with regional arterial chemotherapy perfusion in the treatment of pancreatic cancer. SUBJECTS AND METHODS: The clinical data of 23 patients with pancreatic cancer were retrospectively analyzed, and the patients were divided into two groups. In the observation group, 11 patients were injected with radioactive particles in combination with regional arterial chemotherapy. In the control group, 12 patients were treated with simple regional arterial perfusion chemotherapy. Curative effect, pain relief, survival period, and adverse reactions were compared between the two groups. RESULTS: The proportion of patients was significantly higher in the observation group (complete remission + partial remission) (72.73%) than in the control group (41.67%). The 6-month and 9-month survival rates in the experimental group were 91.7% and 50%, respectively, while those in the control group were 63.6% and 18.2%, respectively, with significantly statistical difference. The 12-month survival rate in the experimental group was 16.7% and was significantly higher than that in the control group (8.3%). The experimental group should greater improvement in pain symptoms than the control group, and there was no statistical difference between the two groups except in complications of 125I radioactive particle implantation. CONCLUSIONS: We conclude that 125I radioactive particle implantation combined with regional arterial perfusion chemotherapy is an effective and comprehensive treatment for advanced pancreatic cancer.

Brain pharmacokinetics of two BBB penetrating bispecific antibodies of different size.

BACKGROUND: Transferrin receptor (TfR1) mediated enhanced brain delivery of antibodies have been studied extensively in preclinical settings. However, the brain pharmacokinetics, i.e. brain entry, distribution and elimination are still not fully understood for this class of antibodies. The overall aim of the study was to compare the brain pharmacokinetics of two BBB-penetrating bispecific antibodies of different size (210 vs 58 kDa). Specifically, we wanted to investigate if the faster systemic clearance of the smaller non-IgG antibody di-scFv3D6-8D3, in comparison with the IgG-based bispecific antibody mAb3D6-scFv8D3, was also reflected in the brain. METHODS: Wild-type (C57/Bl6) mice were injected with 125I-iodinated ([125I]) mAb3D6-scFv8D3 (n = 46) or [125I]di-scFv3D6-8D3 (n = 32) and euthanized 2, 4, 6, 8, 10, 12, 16, or 24 h post injection. Ex vivo radioactivity in whole blood, peripheral organs and brain was measured by γ-counting. Ex vivo autoradiography and nuclear track emulsion were performed on brain sections to investigate brain and parenchymal distribution. Capillary depletion was carried out at 2, 6, and 24 h after injection of [125I]mAb3D6-scFv8D3 (n = 12) or [125I]di-scFv3D6-8D3 (n = 12), to estimate the relative levels of radiolabelled antibody in brain capillaries versus brain parenchyma. In vitro binding kinetics for [125I]mAb3D6-scFv8D3 or [125I]di-scFv3D6-8D3 to murine TfR were determined by LigandTracer. RESULTS: [125I]di-scFv3D6-8D3 showed faster elimination from blood, lower brain Cmax, and Tmax, a larger parenchymal-to-capillary concentration ratio, and a net elimination from brain at an earlier time point after injection compared with the larger [125I]mAb3D6-scFv8D3. However, the elimination rate from brain did not differ between the antibodies. The study also indicated that [125I]di-scFv3D6-8D3 displayed lower avidity than [125I]mAb3D6-scFv8D3 towards TfR1 in vitro and potentially in vivo, at least at the BBB. CONCLUSION: A smaller size and lower TfR1 avidity are likely important for fast parenchymal delivery, while elimination of brain-associated bispecific antibodies may not be dependent on these characteristics.

Combination of 131I-trastuzumab and lanatoside C enhanced therapeutic efficacy in HER2 positive tumor model.

Lanatoside C has a promising anti-tumor activity and is a potential candidate for radiosensitizers. In this study, we have investigated the therapeutic efficacy of the combination of 131I-trastuzumab and lanatoside C for inhibition of human epidermal growth factor receptor 2 (HER2) positive tumor progression in NCI-N87 xenograft model. The combination treatment (131I-trastuzumab and lanatoside C) showed highest cytotoxicity when compared to non-treated control or trastuzumab alone or 131I alone or 131I-trastuzumab alone in vitro. Biodistribution studies using 131I-trastuzumab or combination of 131I-trastuzumab and lanatoside C showed tumor uptake in BALB/c nude mice bearing HER2 positive NCI-N87 tumor xenograft model. The higher tumor uptake was observed in 131I-trastuzumab (19.40 ± 0.04% ID/g) than in the combination of 131I-trastuzumab and lanatoside C (14.02 ± 0.02% ID/g) at 24 h post-injection. Most importantly, an antitumor effect was observed in mice that received the combination of 131I-trastuzumab and lanatoside C (p = 0.009) when compared to control. In addition, mice received lanatoside C alone (p = 0.085) or 131I-trastuzumab alone (p = 0.160) did not significantly inhibit tumor progression compared with control. Taken together, our data suggest that combination of 131I-trastuzumab and lanatoside C might be a potential synergistic treatment for radioimmunotherapy to control the HER2 positive tumor.

Prostate permanent implant brachytherapy with BARC I-125 Ocu-Prosta seeds.

AIM: The aim of this study is implementation and establishment of standard operating procedure for permanent prostate implant brachytherapy technique using BARC I-125 Ocu-Prosta seeds. MATERIALS AND METHODS: The transrectal ultrasound (US)-guided procedure was used for permanent implant procedure. The Best® Sonalis™ US Imaging System and Best NOMOS™ Treatment Planning system was used for volume study and implant procedure. The BARC provided I-125 Ocu-Pro radioactive seeds were implanted into the patient with help of Mick@ Applicator. The implant was performed based on pre-implant dosimetry and intraoperative planning performed during implant procedure. RESULTS: The necessary quality assurance tests were performed for US system before clinical use. The boost dose of 110 Gy was prescribed to the prostate volume of 34.71 cc. About 48 seeds with activity of 0.35 mCi (each) implanted into the prostate volume with reference to intraoperative planning. At the end of procedure, the patient underwent abdomen fluoroscopic examination, to ensure the seed counts in the prostate volume. The day after the implant, the patient was discharged. One month later a planning computed tomography and treatment planning was performed for seed position and dose verification. CONCLUSIONS: Low dose rate permanent implant brachytherapy has the advantage of being a one-time procedure and the existing long term follow-up supports its excellent outcome and low morbidity. BARC-BRIT is supplying the loose 125I seeds. These seeds can be easily implanted into the patient using Mick applicator. However, the pre-implant seed preparation and implant procedure may result some radiation exposure to staff involved. The radiation dose can be minimized with good practice. This report is one patient pilot study and intended to test the implant systems and standard operative procedure henceforth for permanent implant brachytherapy procedure.