An early phase II study of intratumoral P-32 chromic phosphate injection therapy for patients with refractory solid tumors and solitary metastases

BACKGROUND: In this early Phase II study, the authors investigated the efficacy of intratumoral injection of P-32 chromic phosphate in 17 patients with refractory solid tumors or solitary metastases in terms of response rates and overall survival. METHODS: Seventeen patients (median age, 60 years) with either cytostatic drug-resistant tumors or tumors known to be primarily chemotherapy-resistant were entered into the study. After sonographic determination of the tumor volume, P-32 chromic phosphate (74-555 MBq) was injected into the central part of the tumor under sonographic guidance. Follow-up investigations included serial scintigraphy, sonographic examinations, and hematologic studies. RESULTS: Injection of P-32 chromic phosphate into refractory tumors resulted in remarkable regression. The median survival of all patients was 13 months (range, 8-25 months). The response rate was 71% (12 patients). A complete remission was seen in 7 patients (41%), and the rate of partial remissions was 29% (5 patients). However, 5 patients (30%) did not respond to the treatment. In one patient thrombocytopenia was observed, but no other side effects were apparent. Important pathologic and anatomic changes within the tumor tissue were demonstrated in solitary liver metastases of gastrointestinal malignancies excised in second-look operations. In all cases examined, formation of a cyst within the area of central activity, surrounded by a centrifugal necrotic ring and a marginal fibrotic structure, was found. CONCLUSIONS: Lack of persistent systemic or local side effects, as well as noteworthy efficacy, are properties of this optimal regional treatment modality with P-32 chromic phosphate. This modality deserves consideration for further clinical trials.     

A novel approach to brachytherapy in hepatocellular carcinoma using a phosphorous32 (32P) brachytherapy delivery device--a first-in-man study

PURPOSE: While potentially very useful, percutaneously delivered brachytherapy of inoperable intra-abdominal solid tumors faces significant technical challenges. This first-in-man study is designed to determine the safety profile and therapeutic efficacy of a novel phosphorous (32P) brachytherapy device (BrachySil) in patients with unresectable hepatocellular carcinoma. METHODS AND MATERIALS: Patients received single percutaneous and transperitoneal implantations of BrachySil under local anesthesia directly into liver tumors under ultrasound or computed tomographic guidance, at an activity level of 4 MBq/cc of tumor. Toxicity was assessed by the nature, incidence, and severity of adverse events (Common Toxicity Criteria scores) and by hematology and clinical chemistry parameters. Target tumor response was assessed with computed tomographic scans at 12 and 24 weeks postimplantation using World Health Organization criteria. RESULTS: Implantations were successfully carried out in 8 patients (13-74 MBq, mean 40 MBq per tumor) awake and under local anesthesia. Six of the 8 patients reported 19 adverse events, but no serious events were attributable to the study device. Changes in hematology and clinical chemistry were similarly minimal and reflected progressive underlying hepatic disease. All targeted tumors were responding at 12 weeks, with complete response (100% regression) in three lesions. At the end of the study, there were two complete responses, two partial responses, three stable diseases, and one progressive disease. CONCLUSION: Percutaneous implantation of this novel 32P brachytherapy device into hepatocellular carcinoma is safe and well tolerated. A significant degree of antitumor efficacy was demonstrated at this low dose that warrants further investigation.     

Dependence of the frequency distribution around a sphere on the voxel orientation

Microscopically small magnetic field inhomogeneities within an external static magnetic field cause a free induction decay in magnetic resonance imaging that generally exhibits two transverse components that are usually summarized to a complex entity. The Fourier transform of the complex-valued free induction decay is the purely real and positive-valued frequency distribution which allows an easy interpretation of the underlying dephasing mechanism. Typically, the frequency distribution inside a cubic voxel as caused by a spherical magnetic field inhomogeneity is determined by a histogram technique in terms of subdivision of the whole voxel into smaller subvoxels. A faster and more accurate computation is achieved by analytical expressions for the frequency distribution that are derived in this work. In contrast to the usually assumed simplified case of a spherical voxel, we also consider the tilt angles of the cubic voxel to the external magnetic field. The typical asymmetric form of the frequency distribution is reproduced and analyzed for the more realistic case of a cubic voxel. We observe a splitting of frequency distribution peaks for increasing tilt of the cubic voxel against the direction of the external magnetic field in analogy to the case for dephasing around cylindrical, vessel-like objects inside cubic voxels. These results are of value, e.g., for the analysis of susceptibility-weighted images or in quantitative susceptibility imaging since the reconstruction of these images is performed in cubic-shaped voxels.     

婴幼儿皮肤血管瘤P-32放射治疗的临床观察

目的：探讨P-32放射治疗婴幼儿皮肤血管瘤的临床效果及不良反应。方法：观察38例婴幼儿P-32放射治疗后的治疗效果及不良反应。结果：P-32放射治疗婴幼儿血管瘤一次治愈率76.3%,有效率100%。治疗中要及时注意皮肤局部损伤情况。结论：P-32放射治疗婴幼儿皮肤血管瘤方法有效,不良反应。     

婴幼儿皮肤血管瘤P-32放射治疗的临床观察

目的:探讨P-32放射治疗婴幼儿皮肤血管瘤的临床效果及不良反应.方法:观察38例婴幼儿P-32放射治疗后的治疗效果及不良反应.结果:P-32放射治疗婴幼儿血管瘤一次治愈率76.3%,有效率100%.治疗中要及时注意皮肤局部损伤情况.结论:P-32放射治疗婴幼儿皮肤血管瘤方法有效,不良反应.     

32P胶体体外诱导颅咽管瘤细胞凋亡

  目的   探讨32P胶体对颅咽管瘤（craniopharyngioma,CP）体外培养细胞诱导凋亡作用及剂量效应和时间效应关系。   方法   通过原代细胞培养获得CP有限传代细胞系,经不同浓度32P胶体处理不同时间后,应用MTT比色法绘制细胞存活率曲线。流式细胞仪定量检测细胞凋亡率。Hoechst 33342荧光染色检测凋亡细胞形态。TUNEL荧光染色检测DNA特征改变。透射电子显微镜（TEM）检测细胞超微结构。   结果   Hoechst 33342荧光染色、TUNEL荧光染色、TEM均证实32P胶体确能引起CP细胞产生凋亡。随着32P胶体处理浓度（0~14.80 MBq/mL）及时间（1~14 d）的增加,CP细胞存活率减少、凋亡率增高。   结论   32P胶体能明显抑制CP体外培养细胞生长并诱导凋亡,剂量越大及处理时间越长其杀伤作用越强。      

Effects of radiosynovectomy with p-32 colloid therapy in hemophilia and rheumatoid arthritis

AIM: The aim of this study was to assess the effects of treatment with our locally produced P-32 colloidal suspension on knee synovitic inflammations of hemophilic and rheumatoid arthritis (RA) patients, as well as to compare results with chemical synovectomy or corticoid intra-articular injections and evaluate the cost-benefit ratio. MATERIALS AND METHODS: Thirty-six hemophilic male patients, 4-28 years of age and sent by the Hemophilic Foundation (Buenos Aires, Argentina), were enrolled for knee radiosynovectomy (RS) with P-32 colloid (26 patients), or the antibiotic rifampicin with the cooperation of orthopaedists (10 patients). Parents' informed consent was obtained. The following procedures were performed: routine blood tests, X-ray, ultrasound, a 3-phase bone scan, plus monthly methylene diphosphonate (MDP) controls. Patients were included in this study only if several knee episodes had occurred. Exclusion criteria included bone destruction and big Baker's cyst. Twelve RA patients were included, with similar selection criteria: 6 RA patients received P-32 therapy, and the other 6 patients intra-articular corticoids. Clinical, blind evaluation (state of joint involvement, pain, motility, requirements of antihemophilic factors, corticoids, or analgesics) was registered in follow-up charts. If required, joint aspiration was carried out. Intra-articular instillation of saline plus flushing was done before the needle was withdrawn. P- 32 Bremsstrahlung emission was used in the gamma camera for early and late imaging to confirm the absence of leakage. For intra-articular chemical injections therapy, 4 MBq of Tc-99m MAA (macroaggregates) was used. Immobilization and relative rest for 72 hours followed the procedures. RESULTS: There were neither local or systemic effects, nor leakage during P-32 treatment. Intra-articular rifampicin and corticoids procedures required frequent injections. Comparison of regions of interest (ROIs) in treated knees during soft-tissue scintigraphies in pre- and post-third MDP control showed knee improvement. The follow-up evaluation demonstrated an increase in joint motion, diminished volume, and less requirement and frequency of the use of antihemophilic factors (AHF) in 80% of the radiosynovectomies (21 of 26), thus lowering health costs. Five female RA patients (5 of 6) had decreased joint swelling and pains, resulting in increased joint motion. CONCLUSIONS: Radiosynovectomy in RA showed a 3-month pain palliative effect. One intra-articular knee radiosynoviorthesis in haemophilic patients provides a more than 3- month relief of symptoms after treatment with locally produced P-32 (11 patients). This turned out to be a safe, economic alternative procedure in emerging nations where the availability of AHF is difficult and expensive.     

电子线斜入射对剂量分布影响的分析

目的　量化分析不同能量电子线在斜入射情况下对剂量分布的影响。方法　在水模体中 ,测量束流中心轴上不同相对剂量值的深度 ;并测量 80 %和 5 0 %等剂量线的倾斜角度 ;将电子线在不同斜入射角度时的这些测量数据与垂直入射时的测量数据进行比较。结果　①电子线斜入射角度越大 ,最大剂量点深度和 90 %、80 %、5 0 %及 10 %的深度越小 ;②能量越高 ,斜入射对最大剂量点深度和 90 %、80 %、5 0 %及 10 %的深度影响越大 ;③斜入射对相对剂量分布的影响还与射野大小有关 ,射野越大 ,最大剂量点深度和 90 %、80 %、5 0 %及 10 %的深度变化越小 ;④在相同的斜入射条件下 ,电子线能量的改变比射野大小的改变对相对剂量分布的影响要大 ;⑤在斜入射时 ,80 %和 5 0 %等剂量线会向有空气隙的一侧倾斜 ,并且倾斜角度要比斜入射角度大。结论　斜入射不仅使最大电离深度值减小 ,而且使电子线穿透能力减弱 ;电子线穿透能力的减弱程度与电子线能量和射野大小有关 ;临床上要充分考虑在斜入射时 80 %和 5 0 %等剂量线的横向移动 ,否则很容易造成肿瘤靶区的漏照射 ,从而导致肿瘤的局部复发。     

Dose distribution of neutron beam and chromosome analysis

Chromosome analysis using peripheral lymphocytes is a sensitive and reliable indicator of the biological effect of radiation at low radiation doses. In the present study, using this chromosome aberration analysis, we tried to investigate the radiation dose distribution within and around the radiation field of a 6 MeV neutron beam. The efficient induction of dicentrics and rings at the irradiation of neutrons compared to those of gamma or X rays especially in a lower dose range, results in a dominant linear component in the linear quadratic model in the dose response relation of a chromosome aberration formation. A marked increase of RBE (relative biological effectiveness) in a lower dose range of neutrons was demonstrated. The radiation doses of the neutron beam as a function of depth, estimated from the yields of dicentrics and rings in a water phantom revealed a fairly good agreement with doses that were physically obtained. The radiation portal margin of the neutron beam was demonstrated to be not as sharp due to a wide penumbra. This wide penumbra and high RBE value, especially at lower dose range of the neutron beam may contribute to the induction of secondary malignancies in the normal tissue surrounding the tumor mass.     

32p胶体联合地塞米松治疗甲状腺囊肿的疗效

目的:探讨32p胶体联合地塞米松治疗甲状腺囊肿的疗效及临床价值.方法:采用32p胶体联合地塞米松治疗甲状腺囊肿患者103例,患者按甲状腺囊肿的直径大小分为三组,甲状腺囊肿＜2 cm患者45例,2～ ＜3 cm患者38例,3～ ＜4cm患者20例.患者治疗前后均查FT3、FT4、TSH、TG(甲状腺球蛋白)、TM(甲状腺微粒体)及血常规.用超声及甲状腺显像测量囊肿大小.用药1个疗程之后,经医学影像资料未发现囊肿,则判定治愈;经医学影像资料发现囊肿直径缩小超过1/2,则判定有效;囊肿缩小不到治疗前1/2或无变化,则判定无效.采用卡方检验对结果进行统计.结果:三组的治疗效果比较有显著差异,P ＜0.05.三组治疗前后甲状腺激素及血常规检查未发现异常变化,穿刺液未检出癌细胞.治愈病例随访2年未复发.结论:32p胶体联合地塞米松治疗甲状腺囊肿安全,疗效确切,治愈率高,易被患者接受,具有重要的临床价值.     

Comparative analysis of 8-oxo-2' -deoxyguanosine in DNA by 32P- and 33P- postlabeling and electrochemical detection

8-Oxo-2'-deoxyguanosine (8-oxo-dG) is emerging as a useful marker for oxidative DNA damage. Reported basal levels determined by 32P- postlabeling (PPL) method were 10-fold or more higher than those obtained with HPLC/electrochemical detection (ECD). This discrepancy was investigated. In commercial calf thymus DNA, levels of 4 +/- 1 and 64 +/- 14 8-oxo-dG per 10(6) 2'-deoxynucleosides (dN) were measured by the standard HPLC/ECD and PPL methods, respectively. DNA digestion by micrococcal nuclease/spleen phosphodiesterase and nuclease P1 (as used in the standard PPL method), followed by ECD analysis resulted in a level of 8 +/- 3. In calf thymus DNA spiked with chemically synthesized 8-oxo-dGp to give an increment of 9 8-oxo-dG/10(6) dN, the added standard produced a significant increase with HPLC/ECD but not PPL. After spiking the DNA with 90 8-oxo-dG/10(6) dN, the added 8-oxo-dGp was detectable also with PPL, with a labeling efficiency of 65%. In order to investigate the role of ionizing radiation from 32P for the higher 8-oxo-dG levels in PPL, incubation times and amounts of radioactivity in the phosphorylation reaction with commercial dGp were increased, and external irradiation of commercial dG with 32P was investigated. All modifications resulted in higher values of 8-oxo-dG measured, but the effect was not large enough to fully explain the discrepancy between PPL and HPLC/ECD. Using [gamma-33P]ATP instead of [gamma-32P]ATP or adding [33P]phosphate to a 32P-PPL assay resulted in even higher levels of 8-oxo-dG measured. The increase in 8-oxo-dG levels during the PPL workup is attributed to the presence and oxidation of unmodified dGp in the reaction mixture. For a determination of true basal levels, the PPL method will have to be modified, including the removal of dGp prior to the phosphorylation reaction.      

P-32持续低剂量率辐射对外周血淋巴细胞染色体的损伤研究

目的:探讨P-32持续低剂量率辐射对外周血淋巴细胞的染色体损伤.方法:应用不同活度(0、0.01、0.1、0.5、2.7MBq)的放射性P-32胶体溶液,加入6ml的外周血淋巴细胞培养液中,培养3天后进行染色体分析.结果:0.01、0.1、0.5 MBq的P-32持续低剂量率辐射均造成染色体不稳定畸变(双着丝粒、着丝环、无着丝粒断片),随放射性活度增加而增加;2.7MBq的P-32辐射剂量较大,染色体形成率很低.结论:0.01、0.1、0.5 MBq的P-32持续低剂量率辐射可以造成染色体不稳定畸变,随辐射剂量增加畸变率增加;2.7MBq P-32的辐射剂量过大,染色体形成率很低不利于染色体畸变分析.     

Intracavitary brachytherapy using stereotactically applied phosphorus-32 colloid for treatment of cystic craniopharyngiomas in 53 patients

This paper summarizes outcomes of a single-center study of intracavitary brachytherapy (IBT) with stereotactically applied phosphorus-32 ((32)P) colloid for treatment of cystic craniopharyngiomas. We assessed its efficacy and safety, on the basis of clinical and radiological outcomes in one of the largest reported patient series. Between 1992 and 2011, 53 patients were treated with IBT, 14 without previous treatment and 39 who had previously been treated for recurrent cysts. Intervention was performed by applying 200?Gy to the internal cyst wall (median volume 6.1?ml). Median clinical and radiological follow-up were 60.2 and 53.0?months, respectively. Actuarial tumor cyst control was 86.0?±?5.3?% at 12, 24, and 60?months. Actuarial out-of-field control (development of new cysts or progression of solid tumor parts) was 90.9?±?4.3, 84.0?±?5.6, and 54.5?±?8.8?% after 12, 24, and 60?months, respectively. Corresponding actuarial overall progression-free survival was 79.4?±?6.1, 72.4?±?6.8, and 45.6?±?8.7?% at 12, 24, and 60?months, respectively. Visual function improved for 12 patients (23.5?%), remained unchanged for 34 patients (66.7?%), and worsened for five patients (9.8?%), correlating with tumor progression in each case. Endocrinological deterioration occurred for ten patients (19.6?%); for nine patients this was a result of tumor progression or after tumor resection and for one it was attributed to irradiation. Within six months of IBT seven patients (13.7?%) experienced transient neurological deficits and two patients (3.9?%) deteriorated permanently (hemiparesis and third nerve palsy). Stereotactically applied (32)P is highly efficacious for control of cystic components of craniopharyngiomas and is associated with a low risk of permanent morbidity. The procedure does not, however affect the development of new cysts or the progression of solid tumor parts.     

Detection of DNA adducts in human nasal mucosa tissue by 32P- postlabeling analysis

Nasal epithelium is an easily accessible tissue that is potentially useful for human biomonitoring studies aimed at evaluating exposure to airborne carcinogens. We have devised a simple technique, which causes minimum distress to the informed patient, to obtain very small but sufficient biopsies from the inferior or middle turbinate head. DNA adducts were measured by 32P-postlabeling assay in nasal mucosa of nine cigarette smokers (including two subjects who had given up smoking shortly before sampling), two former smokers and 10 non-smoker healthy donors. None of the subjects reported other recent exposures to mutagens or carcinogens. Using the nuclease P1 technique, a mean adduct level of 4.8/10(8) bases and a specific spot pattern, the diagonal radioactive zone, were found in smokers, whereas non-smokers showed a significantly lower global level of DNA adducts, i.e. 1.4/10(8) bases, and no diagonal zone. Another important result was the presence of a significant association between DNA adduct level and the number of cigarettes smoked daily. These preliminary findings suggest that the level of DNA adducts measured from biopsies of the nasal mucosa is a reliable marker of exposure to cigarette smoking and uphold its use in biomonitoring exposures to other airborne DNA binding compounds.      

肿瘤内注射32P-玻璃微球后注射剂量与生物效应的关系

目的 :为了解小鼠肿瘤内直接注射不同剂量 32P -玻璃微球(32P -GTMS)后 ,不同时间肿瘤组织的生物效应。方法 :采用昆明鼠作为实验动物 ,腋部皮下接种S180肿瘤细胞 ,7～10天后在注射部位长出实体瘤块。将36只带瘤鼠分成三个剂量组 ,分别向各组鼠瘤块中心注射不同剂量(37MBq,74MBq,148MBq)的 32P -玻璃微球碘油悬浮液50μl ,在注射后不同时间(7天 ,14天 ,21天 ,28天)分批杀死各剂量组小鼠 ,取出瘤块 ,观察瘤体大小及病理变化。结果 :32P -玻璃微球具有明显的肿瘤抑制和杀伤作用 ,它的有效杀伤半径约为3.5～4mm ,有效杀伤半径不随剂量的增加而增大。结论 :32P -玻璃微球是一种有应用前景的肿瘤治疗药物     

Dose distribution of narrow beam irradiation for small lung tumor

: To aid in the selection of incident X-ray energy for stereotactic irradiation (STI) of lung tumor, dose distribution was investigated in a model of a thorax embedded with a tumor.

: The dose distribution in a thorax model was calculated using the EGS4 Monte Carlo simulation; it was also measured with dosimetric film of a tentative thorax phantom. Uniformity of dose distribution in a tumor region was compared among the results of irradiation for several X-ray energies, and optimal X-ray energy for STI of a lung tumor was discussed.

: Dose distributions in the thorax were obtained. An increase in X-ray energy led not only to an increased dose delivered to the tumor, but also to an increased dose to surrounding normal lung tissue.

: The flat range in dose distribution along the beam axis and in the beam profiles of the tumor increases with decreasing X-ray energy. Consequently, lower energy, rather than higher energy, is recommended for STI of a lung tumor in terms of higher uniformity in the target volume.     

Peritoneal fluid cytology in endometrial cancer: its significance and the role of chromic phosphate (32P) therapy

Between 1978 and 1986, 243 patients (all stages) had peritoneal fluid cytology performed while undergoing total abdominal hysterectomy for endometrial carcinoma; 39 (16%) were found to be positive. At 3 years (median follow-up of 30 months) the disease-free survival (DFS) for the 165 negative cytology clinical Stage I patients was 91% compared to only 56% for the 25 positive cytology patients (p less than .001). Of the 25 Stage I positive cytology patients, 14 with greater than one-third myometrial invasion had a DFS of 30% at 3 years as compared to 87% for negative cytology patients with comparable depth of invasion (p less than .001). There was no difference in DFS between the negative and positive cytology Stage I patients who had one-third or less myometrial invasion. Stage I patients with histologic Grade 2 and 3 had a lower 3 year DFS when cytology positive, 49% and 22%, versus 92% and 79% when cytology negative (p less than .001 and p = .03 respectively). In clinical Stage II patients the 3-year DFS was 21% for those with a positive cytology and 59% with a negative cytology. Fourteen of the 25 clinical Stage I positive cytology patients received 15 mCi of intraperitoneal 32P. At 3 years they had a 68% DFS as compared to 27% for those not receiving 32P (p = 0.01). All 11 patients with superficial myometrial invasion (9 received 32P) remained disease-free. The 4 Stage I patients with deep invasion who received 32P therapy had an improvement in abdominal/pelvic control and DFS when compared to 9 similar patients who did not receive 32P (p = .02). For histologic Grade 2 and 3 patients, there was a 64% 3-year DFS in the 32P treated group and 16% for those not receiving 32P (p = 0.02). Although 32P therapy improved DFS in Stage I positive cytology patients its use along with pelvic radiation therapy can lead to complications. Of 9 Stage I patients receiving 32P as well as pelvic irradiation, 4 experienced serious bowel complications requiring surgery. None of the 5 patients receiving 32P only had a complication.     

Intraperitoneal distribution of 32p-chromic phosphate suspension in the dog

Intraperitoneal administration of radioactive chromic phosphate suspension is receiving renewed attention as a therapeutic treatment to limit metastatic dissemination of ovarian carcinoma. Our study utilized mongrel dogs to approximate the uptake and distribution of 3.0 millicuries 32P-chromic phosphate suspension administered intraperitoneally (IP). Lymph nodes, omentum, retroperitoneum, peritoneum, diaphragm, abdominal wall muscle, pleura, spleen, liver, kidneys, lung, small intestine and blood were sampled for liquid scintillation counting and autoradiography. Whole blood showed the least activity (1800 cpm/100 λ at day one, declining to 280 cpm/100 λ by day 16). Omentum and diaphragm maintained the greatest concentrations (183 x 106 dpm/g and 4 x 106 dpm/g respectively.) These initial high values were 100 times greater than the highest values found for the small intestine, abdominal wall muscle, mediastinal and retroperitoneal lymph nodes and pleura. The peritoneum increased in specific activity until day three (5.9 x 106 dpm/g) and then rapidly declined. Our results show that following IP administration to the dog, 32P suspension is associated with the serous membranes of the peritoneal cavity (most notably omentum, diaphragm, peritoneum and retroperitoneum). This distribution could be valuable in adjuvant tumor therapy since serosal surfaces of the peritoneum (both visceral and parietal) and the omentum are the most common sites of tumor metastases associated with ovarian carcinoma.