Phosphorus kinetics in lambs experimentally infected with Trichostrongylus colubriformis with the use of 32P.

This study was conducted to evaluate the metabolism and phosphorus (P) kinetics in lambs experimentally infected with Trichostrongylus colubriformis using the isotope dilution technique and modelling. Fifteen male lambs (21.1 ±â€¯1.50 kg) of the Santa Inês hair breed of approximately six months old, distributed in the treatments infected (I, n = 8) and control (C, n = 7) were used. The infected lambs received serial infections with 5000 T. colubriformis larvae, three times per week, for 3 weeks (45 000 T. colubriformis total larvae). After 66 days of the last inoculation of infective larvae, 6.6 MBq of 32P were injected in each lamb to evaluate the P kinetics. Blood, faeces and urine samples were collected in the following seven days and the slaughter of lambs were carried out on the last day in order to collect bone and soft tissues (Liver, kidney, heart and muscle) samples. To analyse P flows, the biomathematical model with four compartments (C1 - gastrointestinal tract, C2 - plasma, C3 - bone and C4 - soft tissue) was used. Similar P intake (VI) between treatments (C and I) was verified. Lower absorption of endogenous (Vaf) and dietary P (Vaa), as well as, lower amount of endogenous P (from saliva) that reaches the gastrointestinal tract (VIT), consequently, higher excretion of dietary P (VFD) were verified in infected lambs (P < 0.1). Additionally, in infected lambs, the P bioavailability was lower compared to control lambs. With the lower absorption (VaT) of P in infected lambs, there was, consequently, lower distribution to bones and soft tissues (VeD2) and lower P deposition in the bones (VO+D). It was concluded that P metabolism of lambs infected with T. colubriformis was altered, with reduced intestinal absorption and bioavailability, increased faecal loss and reduced P flow to the bone.

Intracystic bleomycin for cystic craniopharyngiomas in children.

BACKGROUND: Craniopharyngiomas are the most common benign histological tumours to involve the hypothalamo-pituitary region in childhood. Cystic craniopharyngiomas account for more than 90% of the tumours. The optimal treatment of cystic craniopharyngioma remains controversial. Radical resection is the treatment of choice in patients with favourable tumour localisation. When the tumour localisation is unfavourable, a gross-total or partial resection followed by radiotherapy is the main treatment option in adults. However, it presents a risk of morbidity, especially for children. Intracystic bleomycin has been utilised potentially to delay the use of radiotherapy or radical resection, to decrease morbidity. This review is the second update of a previously published Cochrane review. OBJECTIVES: To assess the benefits and harmful effects of intracystic bleomycin in children from birth to 18 years with cystic craniopharyngioma when compared to placebo (no treatment), surgical treatment (with or without adjuvant radiotherapy) or other intracystic treatments. SEARCH METHODS: We searched the electronic databases CENTRAL (2016, Issue 1), MEDLINE/PubMed (from 1966 to February 2016) and EMBASE/Ovid (from 1980 to February 2016) with pre-specified terms. In addition, we searched the reference lists of relevant articles and reviews, conference proceedings (International Society for Paediatric Oncology 2005-2015) and ongoing trial databases (Register of the National Institute of Health and International Standard Randomised Controlled Trial Number (ISRCTN) register) in February 2016. SELECTION CRITERIA: Randomised controlled trials (RCTs), quasi-randomised trials or controlled clinical trials (CCTs) comparing intracystic bleomycin and other treatments for cystic craniopharyngiomas in children (from birth to 18 years). DATA COLLECTION AND ANALYSIS: Two review authors independently performed the study selection, data extraction and 'Risk of bias' assessment. We used risk ratio (RR) for binary data and mean difference (MD) for continuous data. If one of the treatment groups experienced no events and there was only one study available for the outcome, we used the Fischer's exact test. We performed analysis according to the guidelines in the Cochrane Handbook for Systematic reviews of Interventions. MAIN RESULTS: We could not identify any studies in which the only difference between the treatment groups was the use of intracystic bleomycin. We did identify a RCT comparing intracystic bleomycin with intracystic phosphorus(32) ((32)P) (seven children). In this update we identified no additional studies. The included study had a high risk of bias. Survival could not be evaluated. There was no clear evidence of a difference between the treatment groups in cyst reduction (MD -0.15, 95% confidence interval (CI) -0.69 to 0.39, P value = 0.59, very low quality of evidence), neurological status (Fisher's exact P value = 0.429, very low quality of evidence), third nerve paralysis (Fischer's exact P value = 1.00, very low quality of evidence), fever (RR 2.92, 95% CI 0.73 to 11.70, P value = 0.13, very low quality of evidence) or total adverse effects (RR 1.75, 95% CI 0.68 to 4.53, P value = 0.25, very low quality of evidence). There was a significant difference in favour of the (32)P group for the occurrence of headache and vomiting (Fischer's exact P value = 0.029, very low quality of evidence for both outcomes). AUTHORS' CONCLUSIONS: Since we identified no RCTs, quasi-randomised trials or CCTs of the treatment of cystic craniopharyngiomas in children in which only the use of intracystic bleomycin differed between the treatment groups, no definitive conclusions could be made about the effects of intracystic bleomycin in these patients. Only one low-power RCT comparing intracystic bleomycin with intracystic (32)P treatment was available, but no definitive conclusions can be made about the effectiveness of these agents in children with cystic craniopharyngiomas. Based on the currently available evidence, we are not able to give recommendations for the use of intracystic bleomycin in the treatment of cystic craniopharyngiomas in children. High-quality RCTs are needed.

Intracystic bleomycin for cystic craniopharyngiomas in children.

BACKGROUND: Craniopharyngiomas are the commonest benign histological tumours to involve the hypothalamo-pituitary region in childhood. Cystic craniopharyngiomas comprise more than 90% of the tumours. The optimal treatment of cystic craniopharyngioma remains controversial. Radical resection is the treatment of choice in patients with favourable tumour localisation. When the tumour localisation is unfavourable, a gross-total or partial resection followed by radiotherapy is the main treatment option in adults. However, it presents a risk of morbidity, especially for children. Intracystic bleomycin has been utilised potentially to delay the use of radiotherapy or radical resection, to decrease morbidity. This review is an update of a previously published Cochrane review. OBJECTIVES: To assess the benefits and harmful effects of intracystic bleomycin in children from birth to 18 years with cystic craniopharyngioma when compared to placebo (no treatment), surgical treatment (with or without adjuvant radiotherapy) or some other intracyctic treatments. SEARCH METHODS: We searched the electronic databases CENTRAL (2014, Issue 1), MEDLINE/PubMed (from 1966 to March 2014) and EMBASE/Ovid (from 1980 to March 2014) with pre-specified terms. In addition, we searched the reference lists of relevant articles and reviews, conference proceedings (International Society for Paediatric Oncology 2005-2013) and ongoing trial databases (Register of the National Institute of Health and International Standard Randomised Controlled Trial Number (ISRCTN) register) in May 2014. SELECTION CRITERIA: Randomised controlled trials (RCTs), quasi-randomised trials or controlled clinical trials (CCTs) comparing intracystic bleomycin and other treatments for cystic craniopharyngiomas in children (from birth to 18 years). DATA COLLECTION AND ANALYSIS: Two review authors independently performed the data extraction and 'Risk of bias' assessment. We used risk ratio (RR) for binary data and mean difference (MD) for continuous data. We planned that if one of the treatment groups experienced no events and there was only one study available for the outcome, we would use the Fischer's exact test. MAIN RESULTS: We could not identify any studies in which the only difference between the treatment groups was the use of intracystic bleomycin. We did identify a RCT comparing intracystic bleomycin with intracystic phosphorus(32) ((32)P) (n = 7 children). The trial had a high risk of bias. Survival could not be evaluated. There was no evidence of a significant difference between the treatment groups in cyst reduction (MD -0.15, 95% confidence interval (CI) -0.69 to 0.39, P value = 0.59), neurological status (Fisher's exact P value = 0.429), 3rd nerve paralysis (Fischer's exact P value = 1.00), fever (RR 2.92, 95% CI 0.73 to 11.70, P value = 0.13) or total adverse effects (RR 1.75, 95% CI 0.68 to 4.53, P value = 0.25). There was a significant difference in favour of the (32)P group for the occurrence of headache and vomiting (Fischer's exact P value = 0.029 for both outcomes). AUTHORS' CONCLUSIONS: Since we identified no RCTs, quasi-randomised trials or CCTs of the treatment of cystic craniopharyngiomas in children in which only the use of intracystic bleomycin differed between the treatment groups, no definitive conclusions could be made about the effects of intracystic bleomycin in these patients. Only one low-power RCT comparing intracystic bleomycin with intracystic (32)P treatment was available, but no definitive conclusions can be made about the effectiveness of these agents in children with cystic craniopharyngiomas. Based on the currently available evidence, we are not able to give recommendations for the use of intracystic bleomycin in the treatment of cystic craniopharyngiomas in children. High-quality RCTs are needed.

[A 32P application device for the treatment of condyloma acuminatum in the rectum].

OBJECTIVE: To investigate the use of a 32P application device (AD) in the treatment of condyloma acuminatum (CA) in the rectum, and to compare its clinical effect with that of the microwave therapy. METHODS: This study included 107 cases of CA in the rectum, 99 males and 8 females, aged 21-58 (33.6 +/- 9.4) years. Forty-six of the patients (the AD group) were treated with a self-made 32P application device, which, as a tube-shaped carrier of radionuclide 32P colloid, was fixed in the rectum at the diseased part for medication at 4.9-8.2 Gy for 3-5 hours once and 1-2 times a week. The other 61 (the microwave group) were treated by microwave burning under local anesthesia. Both groups of patients were followed up for over 3 months for comparison of the therapeutic results and observation of the stability and reliability of the 32P application device. RESULTS: The rates of cure, reoccurrence and adverse reaction were 84, 8%, 13.0% and 8.7% in the AD group, compared with 40.3%, 55.7% and 75.4% in the microwave group, with statistically significant differences between the two groups (P < 0.01). CONCLUSION: The 32P application device, with its advantages of low cost, easy operation, good effect, high safety and reliability, low recurrence, fewer adverse events and good acceptability, is highly valuable for the treatment of CA in the rectum.

32P as an adjunct to standard therapy for locally advanced unresectable pancreatic cancer: a randomized trial.

This prospective randomized trial was undertaken to determine the added efficacy of (32)P in treating locally advanced unresectable pancreatic cancer. Thirty patients with biopsy proven locally advanced unresectable adenocarcinoma of the pancreas were assessable after receiving 5-fluorouracil and radiation therapy with or without (32)P, followed by gemcitabine. Intratumoral (32)P dose was determined by tumor size and volume and was administered at months 0, 1, 2, 6, 7, and 8. Tumor cross-sectional area and liquefaction were determined at intervals by computed tomography scan. Tumor liquefaction occurred in 78% of patients receiving (32)P and in 8% of patients not receiving (32)P, although tumor cross-sectional area did not decrease. Serious adverse events occurred more often per patient for patients receiving (32)P (4.2 +/- 3.1 vs. 1.8 +/- 1.9; p = 0.03) leading to more hospitalizations. Death was because of disease progression (23 patients), gastrointenstinal hemorrhage (4 patients), and stroke (1 patient). One patient not receiving (32)P and one receiving (32)P are alive at 28 and 13 months, respectively. (32)P did not prolong survival (7.4 +/- 5.5 months with (32)P vs. 11.5 +/- 8.0 months without (32)P, p = 0.16). (32)P promoted tumor liquefaction, but did not decrease tumor size. Intratumoral (32)P was associated with more serious adverse events and did not improve survival for locally advanced unresectable pancreatic cancer.

Internal radiotherapy using 32P colloid or microsphere for refractory solid tumors.

OBJECTIVE: The aim of this work was to study the effectiveness of 32P colloids or microspheres, by arterial interventional administration or stromal injection in the treatment of refractory solid tumors. METHODS: By arterial intervention, under the guidance of computerized tomography, X-ray, ultrasonogram, or under direct vision of the surgical field, 32P microspheres (259-685 MBq) or radioactive colloid (281-666 MBq) was administered to 60 cases with refractory solid tumors. Tumor inhibition rate, side effects, survival period, and so on were observed. RESULTS: The tumor growth was obviously inhibited after the intratumoral injection of 32P colloid. The average survival time in the 60 cases was 35 months with a high tumor inhibition rate (93.4%). Thirty-one cases were completely relieved (51.7%), and 25 cases achieved partial remission (PR, 41.7%). One case with right lobe hepatocellular carcinoma has survived 90 months. The drug was ineffective only in four cases, including one patient who died of gastrointestinal hemorrhage and three of hepatic failure. No other obvious side effects were observed. Intratumoral necrosis, intense fibrosis in the tumor mass, and an integrated capsule encompassing the tumor were revealed by histological examination. CONCLUSIONS: Arterial interventional administration or stromal injection with 32P microspheres or colloid revealed a very fair clinical effectiveness in the treatment of refractory solid tumors. The range of safe effective dosage for 32P glass microspheres and 32P chromic phosphate in one treatment course is 555-740 MBq and 185-370 MBq, respectively.

Determination of biological vector characteristics and nanoparticle dimensions for radioimmunotherapy with radioactive nanoparticles.

Radioimmunotherapy with biological vector labeled with radioactive nanoparticles is investigated from a dosimetric point of view. Beta (32P, 90Y) and low-energy X-ray radionuclides (103Pd) are considered. Dose distributions inside solid tumors have been calculated using MCNPX 2.5.0. Nanoparticle dimensions and biological vector characteristics are also determined in order to reach the 50 Gy prescribed dose inside the entire tumor volume. The worst case of an avascular tumor is considered. Results show that for beta-emitting nanoparticles, a set of data (covering fraction, biological half-life, and nanoparticle radius) can be found within acceptable ranges (those of classical radioimmunotherapy). These sources (with Emax approximately few MeV) can be used for the treatment of tumors with a maximum diameter of about 1 cm. Low-energy X-rays (E<25 keV) can be used to extend the range of tumor diameter to 4-5 cm but require very tight biological vector characteristics.

Design and bioevaluation of a 32P-patch for brachytherapy of skin diseases.

The purpose of this study was to design and evaluate a 32P patch for brachytherapy of skin diseases. We employed Phosphoric-32P-acid and Chromic 32P-phosphate in combination with natural rubber or silicone to produce the patches. Stability studies in vitro to evaluate the leakage of radioactivity, autoradiographic studies to evaluate homogeneity and shielding, as well as therapeutic efficacy in an animal model of skin cancer of the selected 32P patch were performed. The 32P-silicone-patch demonstrated its safety for external application. Tumor growth was arrest and complete regressions of tumors were seen in some other cases with 40 Gy applied in a single-dose scheme. In conclusion, the 32P-silicone-patch is easy to prepare and use in the treatment of skin diseases.

Novel Application of 32P Brachytherapy: Treatment of Angiolymphoid Hyperplasia with Eosinophilia in the Right Auricle with 8-Year Follow-Up.

BACKGROUND: Angiolymphoid hyperplasia with eosinophilia (ALHE) is a distinctive benign vascular disease that can be challenging to treat due to inconsistent results for various treatment modalities such as surgical excision, corticosteroids, radiotherapy, laser therapy, and other therapies, so novel approaches are needed to improve treatment outcomes. MATERIALS AND METHODS: ALHE on the right auricle of a 54-year-old Chinese woman underwent brachytherapy using 32P simple drug membranes for five times. The 32P brachytherapy involving simple drug membranes of brachytherapy began by diluting a 32P solution with 0.9% NaCl solution to produce a radioactivity of 69.2-74.7 MBq/mL(1.87-2.02 mCi/mL). The drug membranes were removed between 48 and 72h after application. There were intervals ranging from 65 to 72d between the membrane application periods, and the last treatment was in June 2010. RESULTS: After the 32P brachytherapy, follow-up results over the course of 8 years were promising. The regional symptoms disappeared, the right preauricular swelling decreased, the subcutaneous nodules decreased in size, the exudate disappeared, and the skin appearance improved. CONCLUSIONS: This case indicated that 32P brachytherapy may represent a novel ALHE treatment method that produces a favorable long-term outcome.

Initial Experience with Intraoperative Phosphorous-32 Brachytherapy During Resection of Malignant Spinal Tumors.

INTRODUCTION: Brachytherapy is a major adjuvant modality for neoplasms, but few have trialed its use for spinal tumors. This study examines perioperative and oncologic outcomes of patients with malignant spinal tumors who underwent resection with intraoperative phosphorous-32 (P32) brachytherapy. METHODS: Consecutive adult patients who underwent P32 brachytherapy during malignant spinal tumor resection were retrospectively identified from 2014 to 2015. Complications, tumor recurrence, and survival were reviewed. A comprehensive review of the literature was performed. RESULTS: A total of 8 patients were included. Average age was 54.3 years, and 25.0% were males. Tumor types included metastatic leiomyosarcoma, chordoma, multifocal recurrent ependymomas, breast metastasis, malignant meningioma, and myxofibrosarcoma. One-half of patients underwent en bloc tumor resection. P32 plaques were applied to 2 sites per patient for mean 13.1 minutes per site with a goal penetration of 10 Gy to 1-mm depth. Perioperative complications occurred in 3 patients (37.5%), including a persistent cerebral spinal fluid leak, deep infection requiring reoperation, and sacral insufficiency fracture. At a mean 25.6 months follow-up, local recurrence rate was 25.0%, and overall survival was 75.0%. Mean time to recurrence was 14.4 months. Survival at 6, 12, 18, and 24 months was 100.0%, 100.0%, 85.7%, and 71.4%, respectively. CONCLUSIONS: The use of P32 is safe and feasible. P32 intraoperative brachytherapy does not seem to increase the rate of complications. The sample size of this series is small with heterogeneity in tumor type, but recurrence and survival outcomes seem promising compared with previous reports. Further clinical trials are needed.

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.

Development of samarium [32P] phosphate colloid for radiosynoviorthesis applications: preparation, biological and preliminary clinical studies experience.

A new therapeutic radio colloid for radiosynoviorthesis (RS) applications is reported. The method of preparation involves the reaction of SmCl3 carrier with carrier added [32P]H3PO4 in the presence of gelatin. The pure colloid was recovered by dialysis purification leading to radiochemical yield of around 90%. The radiochemical purity of the pure colloid formulated in isotonic saline was over 98%, for the usage period of 14 days, as assessed by paper chromatography. Ninety percent of colloid particles were in the size of 1-10 microm as evident from the laser diffraction particle size analysis, ideally suitable for the intended end use. Animal studies revealed complete retention of the radio colloid in the rabbit knee joint. The results of clinical trials in humans are satisfactory and encouraging, satisfactory retention of the colloid in the knee joint and negligible leakage into the systemic circulation.

32-Phosphorus selectively delivered by listeria to pancreatic cancer demonstrates a strong therapeutic effect.

Our laboratory has developed a novel delivery platform using an attenuated non-toxic and non-pathogenic bacterium Listeria monocytogenes that infects tumor cells and selectively survives and multiplies in metastases and primary tumors with help of myeloid-derived suppressor cells (MDSC) and immune suppression in the tumor microenvironment (TME). 32P was efficiently incorporated into the Listeria bacteria by starvation of the bacteria in saline, and then cultured in phosphorus-free medium complemented with 32P as a nutrient. Listeria-32P kills tumor cells through both 32P-induced ionizing radiation and Listeria-induced reactive oxygen species (ROS). The levels of 32P and Listeria were studied in various normal and tumor tissues, at sequential time points after injection of mice with pancreatic cancer (syngeneic model Panc-02). We found that 32P and Listeria predominantly accumulated in tumors and metastases, with their highest accumulation 4 hrs (32P) and 3 days (Listeria) after injection. Listeria also penetrated the transgenic KPC (conditionally express endogenous Kras-G12D and p53-R172H mutant alleles) pancreatic tumors and metastases. This is remarkable since KPC tumors, like human tumors, exhibit a stromal barrier, which prevents most drugs from penetrating the pancreatic tumors. Therapeutic treatment with Listeria -32P resulted in a strong reduction of the growth of pancreatic cancer at early and late stages in Panc-02 and KPC mice. These results highlight the power of Listeria as new delivery platform of anticancer agents to the TME. Not only were therapeutic levels of radioactive Listeria reached in tumors and metastases but the selective delivery also led to minimal side effects.

Low-dose P32 therapy in essential thrombocythemia.

We present a case of an 85-year-old woman with medically refractory essential thrombocythemia and subsequent venous thrombosis. She received conservative phosphorus-32 sodium phosphate therapy for 3 mCi, approximately half the usual dose. One month later, she received a second intravenous phosphorus-32 treatment of 3.5 mCi. She responded successfully to both treatments with drops in her platelet count and experienced no adverse effects. Our case is noteworthy in the effectiveness from a conservative dose while avoiding hematologic complications.

Inhibition of restenosis with beta-emitting radiotherapy: Report of the Proliferation Reduction with Vascular Energy Trial (PREVENT).

BACKGROUND: Intracoronary gamma- and beta-radiation have reduced restenosis in animal models. In the clinical setting, the effectiveness of beta-emitters has not been studied in a broad spectrum of patients, particularly those receiving stents. METHODS AND RESULTS: A prospective, randomized, sham-controlled study of intracoronary radiotherapy with the beta-emitting (32)P source wire, using a centering catheter and automated source delivery unit, was conducted. A total of 105 patients with de novo (70%) or restenotic (30%) lesions who were treated by stenting (61%) or balloon angioplasty (39%) received 0 (control), 16, 20, or 24 Gy to a depth of 1 mm in the artery wall. Angiography at 6 months showed a target site late loss index of 11+/-36% in radiotherapy patients versus 55+/-30% in controls (P:<0.0001). A low late loss index was seen in stented and balloon-treated patients and was similar across the 16, 20, and 24 Gy radiotherapy groups. Restenosis (>/=50%) rates were significantly lower in radiotherapy patients at the target site (8% versus 39%; P:=0.012) and at target site plus adjacent segments (22% versus 50%; P:=0.018). Target lesion revascularization was needed in 5 radiotherapy patients (6%) and 6 controls (24%; P:<0.05). Stenosis adjacent to the target site and late thrombotic events reduced the overall clinical benefit of radiotherapy. CONCLUSIONS: beta-radiotherapy with a centered (32)P source is safe and highly effective in inhibiting restenosis at the target site after stent or balloon angioplasty. However, minimizing edge narrowing and late thrombotic events must be accomplished to maximize the clinical benefit of this modality.

"Edge Effect" of (32)p radioactive stents is caused by the combination of chronic stent injury and radioactive dose falloff.

BACKGROUND: Radioactive stents have been reported to reduce in-stent neointimal thickening. An unexpected increase in neointimal response was observed, however, at the stent-to-artery transitions, the so-called "edge effect." To investigate the factors involved in this edge effect, we studied stents with 1 radioactive half and 1 regular nonradioactive half, thereby creating a midstent radioactive dose-falloff zone next to a nonradioactive stent-artery transition at one side and a radioactive stent-artery transition at the other side. METHODS AND RESULTS: Half-radioactive stents (n=20) and nonradioactive control stents (n=10) were implanted in the coronary arteries of Yucatan micropigs. Animals received aspirin and clopidogrel as antithrombotics. After 4 weeks, a significant midstent stenosis was observed by angiography in the half-radioactive stents. Two animals died suddenly because of coronary occlusion at this mid zone at 8 and 10 weeks. At 12-week follow-up angiography, intravascular ultrasound and histomorphometry showed a significant neointimal thickening at the midstent dose-falloff zone of the half-radioactive stents, but not at the stent-to-artery transitions at both extremities. Such a midstent response (mean angiographic late loss 1.0 mm) was not observed in the nonradioactive stents (mean loss 0.4 to 0.6 mm; P< 0.01). CONCLUSIONS: The edge effect of high-dose radioactive stents in porcine coronary arteries is associated with the combination of stent injury and radioactive dose falloff.

The effect of various therapeutic solutions including colloidal chromic 32P via an intratumoral injection on the tumor physiological parameters of AsPC-1 human pancreatic tumor xenografts in nude mice.

To overcome the physiological barrier in solid tumors (i.e., tumor hypertension), a large volume of material is required via an intratumoral injection. Alternatively, a method of reduction in tumor hypertension is also feasible. In this study, we focused on the physiological response after an intratumoral infusion of various therapeutic agents. Tumor interstitial fluid pressure (TIFP) was intermittently monitored for up to 7 days after treatment using AsPC-1 human pancreatic tumors in nude mice. Macroaggregated albumin (MAA), colloidal chromic 32P (32P-CP), albumin, dexamethasone, 5-fluoro-2'deoxyuridine, dextrose, saline, and trypan blue increased TIFP within approximately 5 min, and TIFP returned to the original level within 1 h, except in the case of MAA and 32P-CP. We also found that the maximal uptake for AsPC-1 tumors in both the exponential and plateau growth phases occurred at approximately 100 min postincubation; the maximum value in the exponential growth phase was approximately 2 times less than that of plateau growth phase (P < 0.01). Therefore, this study supports intralesional 32P-CP brachytherapy for nonresectional pancreatic cancer patients. This may offer a promising treatment modality for delivering high doses of tumor-selective radiation, mainly due to two physiological mechanisms: (a) the high adherence of 32P-CP to the infused regions; and (b) reduction in either tumor blood flow or TIFP by this therapeutic colloid.

Improving patient-specific dosimetry for intravascular brachytherapy.

PURPOSE: Accurate patient-specific dosimetry in intravascular brachytherapy (IVBT) is generally difficult due to the extremely high-dose gradient, complexity of treatment device, and patient-specific geometry (e.g., calcification, stent, curvature, movement of target). The purpose of this study is to analyze quantitatively and systematically the dose effects of calcification, stent, guidewire, and source curvature on clinical dosimetry in an IVBT procedure, and propose a method that can be used to assess these effects in routine clinical practice. METHODS AND MATERIALS: Monte Carlo techniques were used to calculate 3-D dose distribution in both homogeneous and inhomogeneous media for three most commonly used IVBT sources: (90)Sr beta (Novoste), (192)Ir gamma (Cordis/Best), and (32)P beta (Guidant). Dosimetric perturbations in the presence of metallic stents, calcified plaques, metallic guide wires, and source curvature were studied for situations commonly encountered in the clinic. The importance of each of these perturbations and their practical influence on patient-specific dosimetry were analyzed. Factors (plaque, stent, guidewire, and curvature) that may be used to correct/reduce these perturbations were introduced to prevent dosimetric cold spots during IVBT. Practical methods of using these correction factors are proposed. RESULTS: Dose perturbations are significant due to the presence of source curvature, metallic stents, calcified plaques, and metallic guide wires, especially for beta sources. These perturbations can be as high as 30% under normal clinical conditions, although they can be much higher in extreme situations. Empirical relationships of plaque factor with the thickness of calcified plaque, stent factor with stent metallic surface area, guidewire with guidewire thickness, and curvature factor with the bending angle are derived. These relationships are found to be useful in improving clinical dose accuracy in IVBT treatment planning or dose evaluation after treatment. CONCLUSIONS: Significant dose perturbations due to the presence of source curvature, metallic stents, calcified plaques, and guide wires have been found in IVBT for in-stent restenosis. Because it has been reported that, with the current prescriptions for IVBT, higher doses consistently improve treatment outcomes, the empirical method derived from this work can be used to assess cold spots dosimetrically, thus improving patient-specific dosimetry for IVBT.

(32)P radioisotope therapy for recurrent pilocytic astrocytoma.

(32)P is a pure beta-emitter that has a depth of penetration of 2-3 mm and can be useful in the treatment of cystic lesions. Its effectiveness in the treatment of a selected brain tumor is illustrated here.

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.