Un reto multidisciplinar: tratamiento con fósforo-32 en el carcinoma de páncreas localmente avanzado / A multidisciplinary challenge: Therapy with phosphorus-32 for locally advanced pancreatic cancer

El cáncer de páncreas es una enfermedad de pronóstico precario, siendo su supervivencia global la que menos ha mejorado en los últimos 40 años entre todos los cánceres. El adenocarcinoma de páncreas localmente avanzado, sin metástasis a distancia, pero con una afectación vascular limitante, constituye casi un tercio de estos pacientes. En este grupo se concentran gran parte de los esfuerzos investigadores para introducir tratamientos que permitan un aumento de las tasas de rescate quirúrgico y/o de la supervivencia, con 2 objetivos fundamentales: el del control local y el de la prevención de la progresión sistémica. El tratamiento intratumoral con micropartículas de fósforo-32, guiado por ecoendoscopia y combinado con quimioterapia estándar puede tener beneficios significativos y clínicamente relevantes en estos pacientes y, por tanto, una opción valiosa de tratamiento en una enfermedad en la que existe una necesidad urgente de desarrollar nuevas terapias que nos ayuden a mejorar los resultados (AU)

Pancreatic cancer is a disease with a poor prognosis, and overall survival has improved the least in the last 40 years of all cancers. Locally advanced pancreatic adenocarcinoma, without distant metastasis but with limiting vascular involvement, constitutes almost one third of these patients. This group is the focus of most research efforts to introduce treatments to increase surgical salvage rates and/or survival, with two main objectives: local control and prevention of systemic progression. Intratumoural treatment with phosphorus-32 microparticles, guided by echoendoscopy and combined with standard chemotherapy may have significant and clinically relevant benefits in these patients, and therefore a valuable treatment option in a disease where there is an urgent need to develop new therapies to help improve outcomes (AU)

Prospective evaluation of phosphorus-32 radiation synovectomy in patients with severe and chronic rheumatoid arthritis unresponsive to conventional medical treatment.

OBJECTIVES: To determine the efficacy of Phosphorus-32 radiation synovectomy in the treatment of patients with severe rheumatoid arthritis (RA) unresponsive to systematic or local medical therapy. METHODS: Twenty-three knees in 16 patients with severe chronic RA were prospectively treated by intra-articular installation of Phosphorus-32 and evaluated at 1, 3, 6, and 12 months. The Western Ontario and McMaster Universities Arthritis index (WOMAC), visual analog scale (VAS), Health Assessment Questionnaire (HAQ), pain scale, and grade of joint effusion and tenderness were assessed. At the 12-month time interval, the treated knees were classified into four categories: excellent response (no symptoms), good response (significant reduction of symptoms), moderate response (slight decrease), and poor response (no change or worsening). RESULTS: Excellent response or good response was observed in 13/23 (56.5%) of the treated knees, moderate response in 2/23 (8.7%) of the treated knees, and poor response in 8/23 (34.8%) of the treated knees. The grades of effusion and tenderness were significantly decreased one-month posttreatment (P< 0.05); however, these changes did not persist at other time intervals (P > 0.05). There was a significant improvement in the HAQ, WOMAC, VAS, and pain scores at all time points compared with baseline, including at the 12-month time interval (P < 0.05). CONCLUSION: Phosphorus-32 radiosynovectomy is an effective therapeutic treatment for patients with RA of the knee unresponsive to conventional pharmacotherapy.

Using synovial volume measurement by MRI to evaluate the effect of 32P Radiation synovectomy on hemophilic arthropathy patients.

OBJECTIVE: To evaluate the potential of synovial membrane volume measurement by MRI in monitoring the effect of radiation synovectomy on patients of Hemophilic Arthropathy (HA). METHODS: We studied 63 diseased joints of 42 HA patients who received hospitalized services at the Hemophilia Diagnosis and Treatment Center of Henan Provincial People's Hospital from May 2011 to January 2015. Unenhanced and enhanced MR scanning of each diseased joint was performed simultaneously. The volumes of synovial membrane of 21 joints from 16 patients before and after being treated with 32P radiation synovectomy (PRS) were measured and compared using image post-processing software and workstation. Two sample matching t test was conducted to analyze the synovial membrane volumes of the same joint measured by unenhanced and enhanced MR, as well as change of MR enhancement ratio after treatments. RESULTS: The synovial membrane volumes measured by unenhanced versus enhanced MR scanning showed no statistical significance. Significant reduction (t = 7.831, p < 0.001) of the synovial membrane volume after treatment (2479.45±46.48 mm3 versus 2983.30±42.87 mm3 before treatment) was observed. MR enhancement ratio of synovial membrane decreased after treatment (0.92±0.06 after vs 1.17±0.07 before treatment) with statistical significance. CONCLUSION: The synovial membrane volume and MR enhancement ratio can be used to monitor patient response to PRS treatment.

Implantation of defined activities of phosphorus 32 with reduced target damage.

Materials doped with the unstable isotope phosphorus 32 are promising candidates for use in brachytherapeutic applications. One way to dope a material with 32P is by ion implantation. However, the bombardment of the target with ions other than 32P due to impurities of the ion beam leads to unnecessary damages of the target, which might reduce its potential for medical applications. Furthermore, implanting a pre-selected activity of an unstable isotope into a target requires the repeated determination of the target's activity, which requires removing the target from the implantation chamber. This prolongs the total implantation time and requires handling the radioactive target multiple times, which in turn increases the risk of accidental exposure. We have incorporated an online-detector system into the implantation chamber of a 60 kV ion implanter that allowed us to determine the activity of the target without removing the target from the implantation chamber. We then used this system to investigate the implantation of ions with m = 38 u-instead of ions with m = 32 u-to reduce the fraction of other ions than 32P implanted into the target to reduce the induced damages.

Thyroid eye disease: what is new to know?

PURPOSE OF REVIEW: The pathophysiology of thyroid eye disease (TED) is still not fully understood. However, recently described risk factors and molecular findings have brought new insights into the mechanisms of TED and could lead to the emerging use of more targeted therapies. This article aims to review the clinical findings of TED, and the most recent advances in our understanding of the risk factors and therapeutic options for TED. RECENT FINDINGS: Smoking has been recently shown to have an impact on specific gene expression involved in several disease-related pathways, which seems to be reversible with smoking cessation. This finding further emphasizes the importance of smoking cessation in the prevention and treatment of TED. Selenium deficiency and high-serum cholesterol have been described to be potential independent risk factors for TED and their management could decrease the incidence and severity of TED. In terms of therapeutic options, immunomodulatory medications have shown some promising results for disease control in TED over the past years, but further randomized prospective studies with larger sample sizes are still needed to prove their efficacy. A new technique of P brachytherapy was shown to have quick therapeutic effects on TED without significant side effects and could be a promising therapy for selected cases of TED. SUMMARY: TED is one of the most common autoimmune inflammatory disorders of the orbit. Although its pathophysiology remains unclear, newly described genetic findings and risk factors could help in explaining its occurrence and guide future therapies. Immunosuppressant medications are increasingly used in the management of TED, but further studies are needed to confirm their effectiveness.

Phosphorus-32 interstitial radiotherapy for recurrent craniopharyngioma: Expressions of vascular endothelial growth factor and its receptor-2 and imaging features of tumors are associated with tumor radiosensitivity.

To investigate the relationship of the expression of vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor-2 (VEGFR-2) and imaging features with the therapeutic efficacy of Phosphorus-32 colloid interstitial radiotherapy in recurrent craniopharyngioma.Thirty-two patients with recurrent craniopharyngioma underwent phosphorus-32 colloid interstitial radiotherapy. The tumor imaging features were classified into 4 types according to the thickness of the cyst wall and signals of the cyst contents as shown by computed tomography (CT) and magnetic resonance imaging (MRI) images. Protein expressions of VEGF and VEGFR-2 in craniopharyngioma tissues were evaluated with immunohistochemistry before radiotherapy. The tumor radiosensitivity was determined at 12 months after the interstitial radiotherapy.VEGF mainly expressed in the tumor cytoplasm, and VEGFR-2 expressed either in vascular endothelial cells or in tumor endothelial cells. VEGF/VEGFR-2 expressions varied significantly in cases sensitive or insensitive to the radiotherapy (VEGF: P = .028; VEGFR-2: P = .017). Tumor imaging features were associated with the therapeutic efficacy of interstitial radiotherapy (P = .000). VEGF expression had no association with the imaging features of tumors (P = .226), but VEGFR-2 expression was associated with the imaging features of tumors (P = .008).Our results confirmed the association among imaging features, VEGFR-2 expressions, and tumor radiosensitivity in craniopharyngiomas. Imaging features and VEGFR-2 expressions may add useful data to the radiosensitive assessment of craniopharyngiomas.

Toward Personalized Dosimetry with 32P Microparticle Therapy for Advanced Pancreatic Cancer.

PURPOSE: To develop a Monte Carlo model for patient-specific dosimetry of 32P microparticle localized internal radionuclide therapy for advanced pancreatic cancer. METHODS AND MATERIALS: Spherical tumor geometries and a pancreatic phantom were modeled, as well as different 3-dimensional non-uniform clinical pancreatic geometries based on patient-specific ultrasound images. The dosimetry simulations modeled the dose distribution due to the energy spectrum of emitted beta particles. RESULTS: The average dose for small (3-cm diameter) and large (6-cm diameter) spherical tumors was 111 Gy (for 7.6 MBq administered activity) and 128 Gy (for 58 MBq), respectively. For the clinical 3-dimensional geometries, on the basis of patient data, the mean doses delivered to the tumor were calculated to be in the range 102 to 113 Gy, with negligible dose to the pancreas for the smallest tumor volumes. The calculated dose distributions are highly non-uniform. For the largest tumor studied, the pancreas received approximately 6% of the tumor dose (5.7 Gy). Importantly, we found that because the smallest tumor studied exhibited the most dynamic changes in volume in response to the treatment, the dose to tumor and pancreas is significantly underestimated if a static tumor volume is assumed. CONCLUSIONS: These results demonstrate the dosimetry of 32P microparticle localized internal radionuclide therapy for pancreatic cancer and the possibility of developing personalized treatment strategies. The results also highlight the importance of considering the effects of non-uniform dose distributions and dynamic change of tumor mass during treatment on the dosimetry of the tumor and critical organs.

WITHDRAWN: Radioisotopes for metastatic bone pain.

BACKGROUND: This is an update of the review published in Issue 4, 2003. Bone metastasis cause severe pain as well as pathological fractures, hypercalcaemia and spinal cord compression. Treatment strategies currently available to relieve pain from bone metastases include analgesia, radiotherapy, surgery, chemotherapy, hormone therapy, radioisotopes and bisphosphonates. OBJECTIVES: To determine efficacy and safety of radioisotopes in patients with bone metastases to improve metastatic pain, decrease number of complications due to bone metastases and improve patient survival. SEARCH METHODS: We sought randomised controlled trials (RCTs) in MEDLINE, EMBASE, CENTRAL, and the PaPaS Trials Register up to October 2010. SELECTION CRITERIA: Studies selected had metastatic bone pain as a major outcome after treatment with a radioisotope, compared with placebo or another radioisotope. DATA COLLECTION AND ANALYSIS: We assessed the risk of bias of included studies by their sequence generation, allocation concealment, blinding of study participants, researchers and outcome assessors, and incomplete outcome data. Two review authors extracted data. We performed statistical analysis as an "available case" analysis, and calculated global estimates of effect using a random-effects model. We also performed an intention-to-treat (ITT) sensitivity analysis. MAIN RESULTS: This update includes 15 studies (1146 analyzed participants): four (325 participants) already included and 11 new (821 participants). Only three studies had a low risk of bias. We observed a small benefit of radioisotopes for complete relief (risk ratio (RR) 2.10, 95% CI 1.32 to 3.35; Number needed to treat to benefit (NNT) = 5) and complete/partial relief (RR 1.72, 95% CI 1.13 to 2.63; NNT = 4) in the short and medium term (eight studies, 499 participants). There is no conclusive evidence to demonstrate that radioisotopes modify the use of analgesia with respect to placebo. Leucocytopenia and thrombocytopenia are secondary effects significantly associated with the administration of radioisotopes (RR 5.03; 95% CI 1.35 to 18.70; Number needed to treat to harm (NNH) = 13). Pain flares were not higher in the radioisotopes group (RR 0.74; 95% CI 0.27 to 2.06). There are scarce data of moderate quality when comparing Strontium-89 (89Sr) with Samarium-153 (153Sm), Rhenium-186 (186Re) and Phosphorus-32 (32P). We observed no significant differences between treatments. Similarly, we observed no differences when we compared different doses of 153Sm (0.5 versus 1.0 mCi). AUTHORS' CONCLUSIONS: This update adds new evidence on efficacy of radioisotopes versus placebo, 89Sr compared with other radioisotopes, and dose-comparisons of 153Sm and 188Re. There is some evidence indicating that radioisotopes may provide complete reduction in pain over one to six months with no increase in analgesic use, but severe adverse effects (leucocytopenia and thrombocytopenia) are frequent.

Short-term clinico-radiological outcome of chronic knee synovitis among haemophilia A patients post phosphorus-32 radiosynoviorthesis.

PURPOSE: Various modes of therapy have been directed at breaking the vicious cycle at early stage of synovitis in haemophilia patients. This study was planned to assess the short-term clinico-radiological outcome of chronic knee synovitis among haemophilia A patients post phosphorus-32 (P-32) radiosynoviorthesis. METHODS: P-32 samarium radiocolloid was injected into the knee and patients were followed up at 1 and 3 months, respectively. Clinical outcomes was assessed using Tegner Lysholm scores (TLSs), Modified Knee Society Clinical Rating System (MKSS) score and circumference of the knee joint. The radiological outcomes were assessed using X-ray, ultrasonography and bone scan. RESULTS: Among the fifteen haemophilia A patients studied, there was statistically significant difference in TLS ( χ2(2) = 27.887 and p value < 0.001), MKSS scores ( χ2(2) = 27.745 and p < 0.001) and circumference of the knee joint ( χ2(2) = 21.333 and p < 0.001) at preoperatively, 1- and 3-month follow-up. There were no changes noted in follow-up X-rays compared with the preoperative X-ray. Ultrasonography showed that clinical improvement was more in suprapatellar and medial parapatellar regions in the last 2 months compared to the first month of follow-up. Post P-32 bone scan showed marked decrease in uptake in the affected knee joint suggestive of radio ablation of synovial tissue. CONCLUSION: P-32 radiosynoviorthesis done for chronic synovitis among haemophilia A patients showed significant improvement in both clinical and radiological parameters. Ultrasonography can be utilized as non-invasive radiological modality for follow-up of P32 response for knee joint.

Preclinical study investigating the potential of low-dose-rate brachytherapy with 32P stents for the prevention of restenosis of paranasal neo-ostia.

PURPOSE: Ostial restenosis is a common cause of failures in paranasal sinus surgery. The aim of the current study was to investigate the use of low-dose-rate brachytherapy to prevent neo-ostial restenosis in an animal model. METHODS AND MATERIALS: In 14 rabbits, maxillary neo-ostia were created and measured. One side each was stented with a regular silicone stent, the other side was either not stented (n = 7) or stented with a phosphorous-32 implanted stent depositing a low-dose radiation of 15 Gy (n = 7) within 1 week, after which all stents were removed. After a period of additional 12 weeks of recovery, the animals were sacrificed, the neo-ostia were again measured, and the areas and histopathologic changes compared in between the groups. RESULTS: After 15-Gy stenting, the mean ostial areas were even slightly enlarged by 5.1% compared to the area at stent removal, whereas a significant reduction in area, indicating a process of restenosis, by 56.1% or 54.0% was seen in the control groups with no stent and normal stent, respectively. Furthermore, no indication for adverse histopathologic radiation effects was seen in the 15-Gy group. CONCLUSIONS: Low-dose-rate brachytherapy with phosphorous-32 doped silicone stents showed promising results in the prevention of neo-ostium restenosis in this proof-of-concept study, indicating that further preclinical and clinical testing may be warranted.

(32)P in the treatment of myeloproliferative disorders.

UNLABELLED: (32)P has been available for the treatment of myeloproliferative neoplasms (MPNs) for over seventy years. It was first used in 1938 by John H Lawrence in the treatment of polycythaemia and chronic leukaemias. With the introduction of agents such as hydroxycarbamide, interferon and anagrelide the role of (32)P has been diminished. Today, Polycythaemia Rubra Vera (PRV) and Essential Thrombocythaemia (ET) remain the only myeloproliferative conditions in which (32)P is indicated. MATERIALS AND METHODS: We carried out a retrospective review of all patients who had received 32P in Northern Ireland over a 24 year period. The time to successful response, duration of response, and associated complications were reviewed. RESULTS: (32)P was successful in inducing remission in 90% of patients. This remission was sustained following one dose without the need for further therapy in 37% of cases. 47% required repeated doses. 26% required recommencement of alternative therapies. No cases of thrombosis, myelofibrosis or acute leukaemia were observed. DISCUSSION: We conclude that (32)P is a well-tolerated and efficacious treatment option in the elderly. We discuss our results compared with previous work in this area. (32)P will continue to be offered to elderly patients in our practice.

Hydroxyapatite (HA) microparticles labeled with (32)P - A promising option in the radiation synovectomy for inflamed joints.

In the present article we describe a systematic approach pursued for the synthesis of (32)P-labeled hydroxyapatite (HA) microparticles (1-10µm size range) using no carrier added (NCA) (32)P produced in a nuclear reactor and animal evaluation of its utility as an expected viable radiopharmaceutical for the treatment of pain intensive arthrosis. NCA (32)P was produced via the (32)S(n,p)(32)P route in nuclear reactor with high radionuclidic purity (99.95±0.01%, n=5). Phosphorus-32-labeled hydroxyapatite microparticles (1-10µm size range) were synthesized with high radiochemical purity (99.0±0.3% n=12) under optimized conditions and the formulation showed excellent in vitro stability in saline as well as in rat serum. Intra-articular administration of the radiolabeled particles in the knee joints of normal Wistar rats showed near-complete retention of activity within the synovial cavity upto 1 month post-administration. The radiochemical formulation thus demonstrated promising features as a radiopharmaceutical for treatment of arthritis with excellent logistic advantage for shipment to sites distant from the production facility thanks to the suitable nuclear decay properties of (32)P.

Iodine-125-labeled DNA-Triplex-forming oligonucleotides reveal increased cyto- and genotoxic effectiveness compared to Phosphorus-32.

PURPOSE: The efficacy of DNA-targeting radionuclide therapies might be strongly enhanced by employing short range particle-emitters. However, the gain of effectiveness is not yet well substantiated. We compared the Auger electron emitter I-125 to the ß--emitter P-32 in terms of biological effectiveness per decay and radiation dose when located in the close proximity to DNA using DNA Triplex-forming oligonucleotides (TFO). The clonogenicity and the induction of DNA double-strand breaks (DSB) were investigated in SCL-II cells after exposure to P-32- or I-125-labeled TFO targeting the glyceraldehyde 3-phosphate dehydrogenase (GAPDH) gene and after external homogeneous exposure to gamma-rays as reference radiation. MATERIALS AND METHODS: TFO were labeled with P-32 or I-125 using the primer extension method. Cell survival was analyzed by colony-forming assay and DNA damage was assessed by microscopic quantification of protein 53 binding protein 1 (53BP1) foci in SCL-II cells. RESULTS: I-125-TFO induced a pronounced decrease of cell survival (D37 at ∼360 accumulated decays per cell, equivalent to 1.22 Gy cell nucleus dose) and a significant increase of 53BP1 foci with increasing decays. The P-32-labeled TFO induced neither a strong decrease of cell survival nor an increase of 53BP1 foci up to ∼4000 accumulated decays per cell, equivalent to ∼1 Gy cell nucleus dose. The RBE for I-125-TFO was in the range of 3-4 for both biological endpoints. CONCLUSIONS: I-125-TFO proved to be much more radiotoxic than P-32-TFO per decay and per unit dose although targeting the same sequence in the GAPDH gene. This might be well explained by the high number of low energy Auger electrons emitted by I-125 per decay, leading to a high ionization density in the immediate vicinity of the decay site, probably producing highly complex DNA lesions overcharging DNA repair mechanisms.

Stereotactic intracavitary brachytherapy with P-32 for cystic craniopharyngiomas in children.

PURPOSE: Although microsurgery remains the first-line treatment, gross total resection of cystic craniopharyngeomas (CP) is associated with significant morbidity and mortality and the addition of external irradiation to subtotal resection proves to achieve similar tumor control. However, concern regarding long-term morbidity associated with external irradiation in children still remains. With this retrospective analysis, the authors emphasize intracavitary brachytherapy using phosphorus-32 (P-32) as a treatment option for children with cystic CP. PATIENTS AND METHODS: Between 1992 and 2009, 17 children (median age 15.4 years; range 7-18 years) with cystic CP underwent intracavitary brachytherapy using P-32. Eleven patients were treated for recurrent tumor cysts; 6 patients were treated primarily. MR imaging revealed solitary cysts in 7 patients; 10 patients had mixed solid-cystic lesions (median tumor volume 11.1 ml; range 0.5-78.9 ml). The median follow-up time was 61.9 months (range 16.9-196.6 months). RESULTS: Local cyst control could be achieved in 14 patients (82 %). Three patients showed progression of the treated cystic formation (in-field progression) after a median time of 8.3 months (range 5.3-10.3 months), which led to subsequent interventions. The development of new, defined cysts and progression of solid tumor parts (out-of-field progression) occurred in 5 patients and led to additional interventions in 4 cases. There was neither surgery-related permanent morbidity nor mortality in this study. The overall progression-free survival was 75, 63, and 52 % after 1, 3, and 5 years, respectively. CONCLUSION: Intracavitary brachytherapy using P-32 represents a safe and effective treatment option for children harboring cystic CP, even as primary treatment. However, P-32 does not clearly affect growth of solid tumor parts or the development of new cystic formations.

In vivo study of the effect of combining endostatin gene therapy with 32P-colloid on hepatocarcinoma and its functioning mechanism.

PURPOSE: To investigate the therapeutic effect of combining 32P colloid radiotherapy with endostatin anti-angiogenesis therapy on hepatocellular carcinoma (HCC) cells. METHODS: HCC mouse models were prepared using H22 cells and randomly divided into four groups. The mice were administered phosphate buffered saline (PBS), (32)Pcolloid, secretory endostatin encoding plasmid and combination of 32P and endostatin, respectively. Seven, 14 and 21 days after treatment the mice were sacrificed. Expression of endostatin was confirmed using western blot. Tumor growth rate, microvessel density (MVD) in the solid tumor and apoptotic index (AI) of tumor cells was analyzed using immunohistochemistry and TUNEL methods. RESULTS: (1): From the western blot results, 1400 bp endostatin specific protein bands were observed in the samples from groups 3 and 4, but not in the other two groups; (2): The tumor growth rate of groups 2, 3 and 4 was significantly decreased compared to group 1 and that of group 4 was significantly lower than group 2 and 3 (3): The MVD of group 1 was greatly higher than in the other groups (4): The AI of group 4 was dramatically higher than in the other groups. CONCLUSIONS: (32)Pcolloid radiotherapy or endostatin anti-angiogenesis therapy were able to inhibit the growth of HCC cells in vivo, while the combination of (32)P and endostatin showed much better therapeutic effect in HCC treatment.

Experimental and theoretical dosimetry of the RIC-100 phosphorus-32 brachytherapy source for implant geometries encountered in the intraoperative setting.

PURPOSE: Experimental and theoretical dosimetry of the RIC-100 phosphorus-32 brachytherapy source is presented for implant geometries that may occur in an intraoperative setting during treatment of localized spinal tumors with temporary superficial radiation. Dose variation, due to source shape and size, is evaluated, and nonideal implant conditions are simulated. METHODS AND MATERIALS: Calibration, depth dose, and dose profiles were evaluated for several implant geometries and source sizes. Experimental measurements were performed using EBT3 gafchromic film. Theoretical calculations were performed using dose point kernel (DPK) formalism, which simulates isotropic, monoenergetic point sources distributed uniformly throughout the source and emitting electrons radially outward. RESULTS: Calibration and depth dose for RIC-100 are independent of source size for diameters >1 cm. Sources should be ordered with physical dimensions ∼0.2 cm larger than the target size, in all dimensions, to deliver >90% prescription dose to target edges. Relative dose profile shape is approximately constant as a function of target depth. Air gaps between the source and target cause narrower dose profile widths and shallower depth dose in the therapeutic range. DPK for RIC-100 agrees with published P-32 kernels, and DPK calculations agree with measurement (within 5%) for many depths and geometries. CONCLUSIONS: Intraoperative placement and measurement dosimetry of RIC-100 require careful setup due to steep dose gradients. Physical source dimensions should be chosen carefully based on treatment site dimensions, and air gaps between source and target should be minimized, to prevent underdosing the target in the lateral extent. Radiological scaling should be used to calculate expected dose when nonwater materials are used in experimental measurements, such as calibration or depth dose.

Phosphorus-32, a clinically available drug, inhibits cancer growth by inducing DNA double-strand breakage.

Radioisotopes that emit electrons (beta particles), such as radioiodine, can effectively kill target cells, including cancer cells. Aqueous 32P[PO4] is a pure beta-emitter that has been used for several decades to treat non-malignant human myeloproliferative diseases. 32P[PO4] was directly compared to a more powerful pure beta-emitter, the clinically important 90Y isotope. In vitro, 32P[PO4] was more effective at killing cells than was the more powerful isotope 90Y (P ≤ 0.001) and also caused substantially more double-stranded DNA breaks than did 90Y. In vivo, a single low-dose intravenous dose of aqueous elemental 32P significantly inhibited tumor growth in the syngeneic murine cancer model (P ≤ 0.001). This effect is exerted by direct incorporation into nascent DNA chains, resulting in double-stranded breakage, a unique mechanism not duplicatable by other, more powerful electron-emitting radioisotopes. 32P[PO4] should be considered for human clinical trials as a potential novel anti-cancer drug.

Determination of surface dose rate of indigenous (32)P patch brachytherapy source by experimental and Monte Carlo methods.

Isotope production and Application Division of Bhabha Atomic Research Center developed (32)P patch sources for treatment of superficial tumors. Surface dose rate of a newly developed (32)P patch source of nominal diameter 25 mm was measured experimentally using standard extrapolation ionization chamber and Gafchromic EBT film. Monte Carlo model of the (32)P patch source along with the extrapolation chamber was also developed to estimate the surface dose rates from these sources. The surface dose rates to tissue (cGy/min) measured using extrapolation chamber and radiochromic films are 82.03±4.18 (k=2) and 79.13±2.53 (k=2) respectively. The two values of the surface dose rates measured using the two independent experimental methods are in good agreement to each other within a variation of 3.5%. The surface dose rate to tissue (cGy/min) estimated using the MCNP Monte Carlo code works out to be 77.78±1.16 (k=2). The maximum deviation between the surface dose rates to tissue obtained by Monte Carlo and the extrapolation chamber method is 5.2% whereas the difference between the surface dose rates obtained by radiochromic film measurement and the Monte Carlo simulation is 1.7%. The three values of the surface dose rates of the (32)P patch source obtained by three independent methods are in good agreement to one another within the uncertainties associated with their measurements and calculation. This work has demonstrated that MCNP based electron transport simulations are accurate enough for determining the dosimetry parameters of the indigenously developed (32)P patch sources for contact brachytherapy applications.

The long-term effects of radioactive phosphorous synoviorthesis on hemophilic arthropathy.

BACKGROUND: Radioactive synoviorthesis was carried out by an injection of radioactive materials into the joint that has been known as a successful alternative treatment to invasive surgical synovectomy. This study was designed to evaluate short-term and long-term results and complications of radioactive synovectomy of hemophilic arthropathy using radioactive phosphorus. MATERIALS AND METHODS: This study was conducted on 40 patients with hemophilic arthropathy. After obtaining clotting factors, the intra-articular injections of radioactive phosphorus were done. Thirteen patients were evaluated during 36 months (short-term follow-up) and 27 patients were followed up for more than 36 months (long-term follow-up). Patients were evaluated for hemarthrosis, factor consumption per month, joint range of motion (ROM) and clinical and radiological involvement grade. RESULTS: The patients mean age was 22.9 ± 6.6 and there were 38 men and 2 women. Consumption of clotting factors was significantly reduced in the short-term follow-up of patients (p < 0.05), but there was no significant difference in the long-term follow-up (p > 0.05). ROM decreased significantly in the long-term follow-up (p < 0.05). Radiologic evaluation showed significantly increased involvement in their joints (p < 0.05). CONCLUSION: Using radioactive synoviorthesis led in decreased consumption of clotting factors and the hemarthrosis incidence in short term but it did not have significant impact on clinical situation (ROM) and radiological findings of hemophilic patients in long-term follow-up.

Estimation of skin dose rate from a catheter bag filled with P-32 solution.

Patients attending for therapy with phosphorus-32 (P-32) may have problems with urinary continence requiring the use of a urinary catheter. P-32 is excreted renally and the contents of the catheter bag will impart a dose to the skin with which the bag is in contact. We simulated a catheter bag filled with P-32-contaminated urine and measured the dose rate per unit activity from the bag. A volume of 25 MBq of P-32 was added to a 500 ml bag of saline and mixed thoroughly. A personal dosimetry badge was fixed to the surface of the bag and left for 48 h before being sent for processing. To account for decay, the cumulative activity in the bag over the 48 h period was calculated and the shallow [Hp(0.07)] dose measured by the badge was divided by the cumulative activity to yield a dose rate per MBq of activity. The measured Hp(0.07) dose was 192.8 mSv, which corresponds to a dose rate per MBq of 169 µSv/h/MBq. This study has shown that the dose rate per MBq from a simulated catheter bag of radioactive phosphorus differs from the dose rates published for other containers. This value may be useful in the risk assessment of P-32 therapy in catheterized patients.