MBq Group Research Articles

Eighteen-Months Safety and Efficacy Following Intraperitoneal Treatment With 224Radium-Labeled Microparticles After CRS-HIPEC in Patients With Peritoneal Metastasis From Colorectal Cancer.

Peritoneal metastasis from colorectal cancer carries a high risk for relapse after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). A novel alpha-emitting radiopharmaceutical (Radspherin) has been designed to deliver short-range radiation to micrometastases and free-floating tumor cells. A Phase 1/2a study evaluated the safety, tolerability, and signal of efficacy of escalating doses of Radspherin injected intraperitoneally after CRS-HIPEC. Eleven patients received 1-4 MBq (Group 1) whereas 12 patients received 7 MBq; nine patients single dose/three patients split-dose (Group 2). Median age was 66.5 and 61.5 years, and median peritoneal cancer index 6 and 7, respectively. One hundred and seventy-eight adverse events were reported, only seven were deemed related to Radspherin. Thirteen serious adverse events (SAEs) were reported in eight patients and no SAEs were related to Radspherin. At 18-months, none of the 12 patients receiving 7 MBq experienced peritoneal recurrences, however four had non-peritoneal recurrences. Across both groups (n = 22), 41% had recurrent disease, only 14% of them in the peritoneum. Radspherin was well tolerated. At 18 months, median disease-free survival has not been reached, and none of the patients receiving the recommended dose (7 MBq) had peritoneal recurrences. The results are encouraging and warrant further clinical evaluation.

Novel astatine (211At)-labelled prostate-specific membrane antigen ligand with a neopentyl-glycol structure: evaluation of stability, efficacy, and safety using a prostate cancer xenograft model.

Prostate-specific membrane antigen (PSMA)-targeted alpha therapy is considered a promising alternative treatment for metastatic castration-resistant prostate cancer (mCRPC). Though astatine-211 (211At) is potentially useful alpha-emitter producible by cyclotrons, its clinical application has been limited by instability and a tendency to deastatination in vivo. To overcome these challenges, we developed [211At]At-NpG-PSMA, a novel PSMA ligand with a neopentyl-glycol structure that enhances in vivo stability against deastatination. This study aimed to evaluate the stability, anti-tumour effect, and safety of [211At]At-NpG-PSMA in mice. Xenograft models were prepared by subcutaneous transplantation of PSMA-positive PC-3 PIP cells into BALB/c nu/nu mice. [211At]At-NpG-PSMA was administered to assess biodistribution, and the anti-tumour effect was evaluated at doses of 0.32, 1.00 and 1.93 MBq in comparison with saline. Histopathological examinations were performed to evaluate damage to normal organs. [211At]At-NpG-PSMA demonstrated high tumour uptake (42.0 ± 13.1%ID/g at 3h) with minimal uptake in non-target tissues, including thyroid, stomach and salivary grands (0.28 ± 0.20%ID, 0.71 ± 0.12%ID/g and 0.88 ± 0.10%ID/g at 3h, respectively). A dose-dependent anti-tumour effect was observed, with tumour volumes increasing by 796.0 ± 437.6% in the control versus 161.0 ± 213.4%, -76.4 ± 19.2% and - 59.5 ± 41.6% in the 0.32, 1.00 and 1.93 MBq groups, respectively, by day 15. Mild renal tubule regeneration was noted in the 1.00 MBq group. [211At]At-NpG-PSMA demonstrated significant stability in vivo and anti-tumour effects with minimal side effects, indicating its potential as a new therapeutic drug for PSMA-targeted alpha therapy in mCRPC.

177Lu]Lu-labeled anti-claudin-18.2 antibody demonstrated radioimmunotherapy potential in gastric cancer mouse xenograft models.

Gastric cancer (GC), one of the most prevalent and deadliest tumors worldwide, is often diagnosed at an advanced stage with limited treatment options and poor prognosis. The development of a CLDN18.2-targeted radioimmunotherapy probe is a potential treatment option for GC. The CLDN18.2 antibody TST001 (provided by Transcenta) was conjugated with DOTA and radiolabeled with the radioactive nuclide 177Lu. The specificity and targeting ability were evaluated by cell uptake, imaging and biodistribution experiments. In BGC823CLDN18.2/AGSCLDN18.2 mouse models, the efficacy of [177Lu]Lu-TST001 against CLDN18.2-expressing tumors was demonstrated, and toxicity was evaluated by H&E staining and blood sample testing. [177Lu]Lu-TST001 was labeled with an 99.17%±0.32 radiochemical purity, an 18.50 ± 1.27 MBq/nmol specific activity and a stability of ≥ 94% after 7 days. It exhibited specific and high tumor uptake in CLDN18.2-positive xenografts of GC mouse models. Survival studies in BGC823CLDN18.2 and AGSCLDN18.2 tumor-bearing mouse models indicated that a low dose of 5.55 MBq and a high dose of 11.10 MBq [177Lu]Lu-TST001 significantly inhibited tumor growth compared to the saline control group, with the 11.1 MBq group showing better therapeutic efficacy. Histological staining with hematoxylin and eosin (H&E) and Ki67 immunohistochemistry of residual tissues confirmed tumor tissue destruction and reduced tumor cell proliferation following treatment. H&E showed that there was no significant short-term toxicity observed in the heart, spleen, stomach or other important organs when treated with a high dose of [177Lu]Lu-TST001, and no apparent hematotoxicity or liver toxicity was observed. In preclinical studies, [177Lu]Lu-TST001 demonstrated significant antitumor efficacy with acceptable toxicity. It exhibits strong potential for clinical translation, providing a new promising treatment option for CLDN18.2-overexpressing tumors, including GC.

Optimization of 201Tl Dosage in a Simultaneous Acquisition Rest 99mTc/Stress 201Tl Dual-Isotope Myocardial Perfusion Single-Photon Emission Computed Tomography with Semiconductor Gamma Camera.

Background: The use of 201Tl in myocardial perfusion single-photon emission computed tomography (SPECT) is predominantly not recommended because of the higher radiation exposure of 201Tl compared to 99mTc agent. However, the advent of new gamma cameras with semiconductor detectors has made it possible to reduce the 201Tl dose and lower radiation exposure. In our hospital, the dose of 201Tl is adjusted according to the patient's body mass index (BMI), with 50 MBq for BMI<25 and 74 MBq for BMI≥25. The dose of 201Tl during simultaneous acquisition dual-isotope myocardial perfusion SPECT (MPS; stress 201Tl and rest 99mTc agent) exceeds 9 mSv/examination when 74 MBq of 201Tl is administered. In order to further reduce the radiation dose, optimization of the 201Tl dose was investigated. Methods: Two hundred and eighty consecutive patients who underwent stress MPS using simultaneous acquisition dual-isotope protocol (SDI protocol) for the estimation of ischemic heart disease were included. Patients with prior myocardial infarction were excluded. Correlations between BMI and acquisition time were determined in patients receiving 50 MBq (n=154) or 74 MBq (n=126) of 201Tl. In addition, linear regression analysis was used to determine the slope and intercept to derive a linear functional equation, and the theoretically optimal 201Tl dose was evaluated. Results: The correlation coefficient between BMI and acquisition time in the 201Tl 50 MBq group was 0.532 (P< 0.00001) and in the 201Tl 74 MBq group was 0.478 (P<0.00001), both showing a positive correlation. Linear regression analysis yielded two equations: y=0.52x-0.32 (201Tl 50 MBq group) and y=0.41x-0.69 (201Tl 74 MBq group). Linear function equation results indicated that patients with BMI between 25 and 30 could be examined within approximately 15 minutes with 50 MBq of 201Tl. Conclusion: Considering examination efficiency, a single acquisition time of less than 15 minutes is ideal. Theoretically, patients with BMI less than 30 could be examined within approximately 15 minutes with 50 MBq of 201Tl.

Preclinical Evaluation of Radiation-Induced Toxicity in Targeted Alpha Therapy Using [211At] NaAt in Mice: A Revisit

We recently reported the dose-dependent therapeutic effect of 211At-NaAt in differentiated thyroid cancer xenograft models. In the present study, we evaluated the radiation-induced toxicity of 211At-NaAt using detailed hematological, biochemical, and histological analyses. Biodistribution of 211At-NaAt was measured in normal ICR mice (n = 12), absorbed doses in the major organs were calculated. Groups of ICR mice (n = 60) were injected with 0.1 MBq or 1 MBq of 211At-NaAt, using saline as the control group (n = 30). Body weight and food intake were followed up for 60 days. Blood cell counts and serum level of biochemical parameters were measured 3, 7, 15, 29, 60 days after injection. Histological analyses of the major organs with hematoxylin and eosin staining were performed. Biodistribution study revealed a high-absorbed dose in the thyroid gland, stomach, bladder, heart, lungs, spleen, kidneys, and testis. The 0.1 MBq group showed no abnormalities. The 1 MBq group showed decreased body weight and food intake. Histological analysis showed atrophy and fibrosis in the thyroid gland, a transient hypospermatogenesis in the testis on day 29 was found in one mouse. Hematological toxicity was mild and transient. The total cholesterol, albumin, and total protein increased with no signs of recovery, which was considered to be caused by hypothyroidism. High-dose administration of 211At-NaAt showed transient toxicity in the white blood cells and testis without severe hematological or renal toxicity, suggesting its tolerable safety as targeted alpha-therapy for differentiated thyroid cancer in the 1 MBq group.

Development of an athyroid mouse model using 131I ablation after preparation with a low-iodine diet

We optimized the protocol for thyroid ablation in living mice using radioactive iodine (RAI) and a low-iodine diet (LID). To examine the effect of LID on thyroid ablation, mice were randomly divided into 4 groups: Vehicle, 131I 2.775 MBq, 131I 5.55 MBq, and LID + 131I 2.775 MBq. The LID group was fed a LID for up to 7 days and then mice in the 131I 2.775, 131I 5.55, and LID + 131I 2.775 MBq groups were intravenously administrated with 131I, respectively. Scintigraphy imaging with 99mTc pertechnetate was performed once in 2 weeks for 4 weeks. After establishment of athyroid mice, control or athyroid mice were injected with human anaplastic thyroid cancer cells co-expressing sodium iodine symporter and enhanced firefly luciferase (ARO/NF) to evaluate RAI uptake. Scintigraphy imaging with 99mTc pertechnetate was performed with ARO/NF tumor-bearing mice. Scintigraphy imaging showed decreased thyroid uptake in the LID + 131I 2.775 MBq group compared to other groups. Scintigraphy images showed that tumor uptake was statically higher in athyroid mice than in control mice. These data suggest that these optimized conditions for thyroid ablation could be helpful to establish an in vivo mouse model.

Effect of 125I seed implantation on the angiogenesis of transplanted human lung adenocarcinoma in nude mice

Objective To investigate the effect and underlying mechanism of radioactive 125I seed implantation on the angiogenesis of transplanted human lung adenocarcinoma in nude mice. Methods An animal model of transplanted human lung adenocarcinoma was established by subcutaneous implanting A549 cells into nude mice. Twenty four tumor-bearing nude mice were randomly divided into 4 groups with different irradiation doses of blank control (without any treatment) and 0 MBq, 22.2 MBq, 29.6 MBq and by embedding radioactive 125I seeds with an 18 G implant needle. Tumor volumes were measured every 4 days until all mice were terminated 30 d later and the tumor growth curve was drawn. The microvessel density (MVD) in the tumor tissue was detected by immunohistochemistry S-P assay. The mRNA and protein levels of VEGF and HIF-1α of each group were detected by RT-PCR and Western blot, respectively. Results After embedding of 125I seeds, the tumor volumes of 22.2 MBq group (886±97) and 29.6 MBq group (590±107) were significantly smaller than those of control group (2 297±149) at 54 d after administration (q=14.117, 17.075, P 0.05). The immunohistochemical CD34-positive staining demonstrated that MVD in 22.2 MBq group (522±119) and 29.6 MBq group (491±121) were decreased significantly compared with control group (922±260) (q=4.826, 5.197, P 0.05). The mRNA expressions of VEGF and HIF-1α in 22.2 MBq group (0.279±0.0659, 0.370±0.0857) and 29.6 MBq group (0.215±0.0620, 0.278±0.0651) were significantly lower than those in the control group (qVEGF mRNA =18.881, 17.211, qHIF-1α mRNA=15.376, 14.733, P 0.05). At the same time, the expression levels of VEGF and HIF-1α protein after 125I seed implantation were also obviously decreased in 22.2 MBq and 29.6 MBq groups (qVEGF=5.848, 6.263, qHIF-1α=6.560, 7.576, P 0.05) and between 22.2 MBq and 29.6 MBq groups(P>0.05). Conclusions Interstitial implantation with 125I seeds may potently inhibit angiogenesis in human lung adenocarcinoma xenografts of nude mice. Key words: Radioisotope 125I seeds; Lung adenocarcinoma; Animal model; Microvessel density

Evaluation of retinol binding protein 4 and carbamoylated haemoglobin as potential renal toxicity biomarkers in adult mice treated with (177)Lu-octreotate.

BackgroundThe kidneys are regarded as one of the main dose-limiting organs in the treatment of neuroendocrine tumours with 177Lu-[DOTA0, Tyr3]-octreotate (177Lu-octreotate), despite the successful use of kidney uptake blocking agents such as lysine and arginine. To avoid renal toxicity but still give each patient as high amount of 177Lu-octreotate as possible, there is a need for methods/biomarkers that indicate renal injury in an early stage of the treatment. The aim of this study was to investigate the potential of using urinary retinol binding protein 4 (RBP4) and carbamoylated haemoglobin (Hb) in blood as biomarkers of nephrotoxic effects on adult mice after 177Lu-octreotate treatment.MethodsAdult BALB/c nude mice were injected with 60 MBq or 120 MBq of 177Lu-octreotate or with saline (control). Urine was collected before injection and concentrations of urinary RBP4 and creatinine were determined 14 to 90 days after injection Blood samples were collected after 90 days, and carbamoylated N-terminal valine in Hb, formed from urea, was measured as valine hydantoin (VH) after detachment from Hb.ResultsThe RBP4 values increased with administered activity and time. For the 60 and 120 MBq groups, statistically significantly higher RBP4 levels (p <0.05) were found at day 60 and 90 compared to baseline, also at day 30 for 120 MBq group. For VH, the mean values were similar for the 60 MBq and control groups, while a small increase was observed for the 120 MBq group; but there were no statistically significant differences between any of the groups (p >0.05). No morphological changes in the kidney tissue were found.ConclusionsUrinary RBP4 is a promising new biomarker for radiation-induced renal toxicity. For the conditions used in this experiment, carbamoylated Hb (from urea) measured as VH may not be a sufficiently sensitive biomarker to be used for renal toxicity.Trial registrationID 326-2008

Quantitative evaluation of the administrated dose affecting image quality in myocardial perfusion SPECT.

Myocardial perfusion imaging (MPI) can provide the valuable cardiac functions.Image quality in nuclear medicine tomography is critically dependent on the activity administered into patients. This study was designed to evaluate the optimum injected dose of 99mTc-MIBI for quantitative assessment of image quality as compared with standard injected dose used for that purpose. The image quality parameters (Contrast, relative noise and contrast to noise ratio) were determined in 32 patients (21 male, 11 female, age 45-60 y) with weight 60 ± 15 kg. Patients were classified into four groups; each one consisted of 8 patients. The first group received 370 MBq, the second one received 555 MBq, the third group received 740 MBq and the last group received 925 MBq. Qualitative assessments of the images revealed equivalent scintigraphic patterns in all patients. There was a significant difference in the image contrast. The image contrast in the 370 MBq group was greater than other groups. The image noise between the four groups was significantly different. It increased with injected dose reduction. Contrast to noise ratio (CNR) was significantly different between 370 MBq and other groups. It is concluded that results from the first group which received 370 MBq are sufficiently similar to those of the fourth group (standard group) which received 925 MBq. Consequently,accurate estimations of differential cardiac functions are possible with the 370 MBq dose.

A Randomized Controlled Trial to Evaluate the Effectiveness of 2 Regimens of Fixed Iodine (131I) Doses for Graves Disease Treatment

To investigate the effectiveness of 2 fixed iodine (¹³¹I) doses for the treatment for Graves hyperthyroidism and their impact on eye disease. We prospectively examined 76 patients who received a fixed dose of 370 MBq (group 1) and 52 patients who received 555 MBq ¹³¹I (group 2). Patients were followed up for 12 months and considered in remission when they were in a stable euthyroid or hypothyroid state in the absence of antithyroid drugs 12 months after ¹³¹I administration. Eight patients with active eye disease received a daily dose of 0.5 mg/kg prednisone per kilogram of body weight at the time of radioiodine therapy for 1 month. The remission rate obtained was similar in groups 1 (73.7%) and 2 (80.8%; P = 0.35). Hypothyroidism was diagnosed in 56.5% of the 370-MBq group and 71.1% of the 555-MBq group patients (P = 0.13). There was no correlation among clinical features, thyroid uptake, antibody levels, serum hormones levels, and outcome. However, logistic regression analysis demonstrated that patients with large thyroid glands had 2.4 times less chance to go into remission (odds ratio; 95% confidence interval = 1.18-4.96). None of the patients developed eye disease during any fixed-dose treatment regimen or worsened their previously diagnosed ophthalmopathy. Fixed doses of 370 MBq and 555 MBq ¹³¹I provided similar remission rates; however, outcome was influenced by the thyroid size. We propose that 370 MBq ¹³¹I should be the routine treatment dose for all Graves disease patients, reserving a dose of 555 MBq ¹³¹I to palpable large goiters, without any additional concern to eye disease.

Axillary sentinel node identification in breast cancer patients: degree of radioactivity present at biopsy is critical

The radioactivity present in the patient (Act(rem) ) at sentinel node (SN) biopsy will depend on injected activity amount as well as on the time interval from tracer injection to biopsy, which both show great variations in the literature. The purpose of this study was to analyse the influence of varying Act(rem) levels on the outcome of axillary SN biopsy in patients with breast cancer (BC). Eight hundred and fifty-eight patients with BC were consecutively referred to SN biopsy, 21% for a same-day and 79% of the patients for a 2-day procedure. Four hundred and nineteen patients underwent scintigraphy and 439 did not. For same-day procedures, 50 MBq (99m) Tc-nanocolloid (Nanocoll(®) ) was injected, and for 2-day procedures 110 MBq. For the analysis of SN biopsy outcome, the patients were divided into three Act(rem) groups: <10 (56% of the patients), 10-20 (23%), and >20 MBq (21%). During surgery, SNs were located using a hand-held gamma probe supported by image information when available and blue dye injection. Pathology included haematoxylin-eosin staining followed by immunohistochemistry. The number of SNs removed (mean value 1·87 versus 2·14, P = 0·0003) and the probability of finding a malignant SN (P = 0·034) were lower in the <10 MBq group of patients compared with higher Act(rem) >20 MBq. Of the 25 patients with SN non-detection, 20 patients had an Act(rem) <10 MBq. Imaging had no significant influence on the number of patients with a malignant SN (P = 0·48). Act(rem) above 10 MBq for nanocolloid tracer appears important for appropriate identification of SNs in patients with BC.

Experimental study of CT guided ³²P-CP-PLLA microparticle implantation in the treatment of rabbit VX2 lung tumor

背景与目的新型放射性植入剂32P-磷酸铬-聚-L-乳酸（32P-CP-PLLA）粒子具有良好的生物相容性和降解性，适用于实体肿瘤的近距离放射治疗。本研究旨在探讨兔VX2肺肿瘤经32P-CP-PLLA粒子瘤体间植入近距离治疗前后PET/CT显像及病理学的变化，分析32P-CP-PLLA粒子植入对荷VX2肺癌兔肿瘤生长及凋亡相关蛋白的影响。方法24只荷瘤兔随机分成4组。每组6只。1组-3组为治疗组；4组为对照组。在CT导引下经皮穿刺将总放射性活度为93 MBq、185 MBq和370 MBq的32P-CP-PLLA粒子分别植入1组、2组和3组肿瘤组织内。对照组不做任何干预。分别在治疗后第0天、第3天、第7天和第14天进行18F-FDG PET/CT显像，观察标准摄取值（standardized uptake value, SUV）的变化。最后1次PET/CT显像后处死荷瘤兔，取出肿瘤组织，进行病理学检查和免疫组织化学分析，比较肿瘤细胞形态和凋亡基因（bcl-2, bax）表达的变化。结果第0天时，治疗组和对照组之间SUVmax无明显差异。治疗后第14天，1组、2组和3组SUVmax值分别为1.1±0.19、0.80±0.10和2.85±0.15，均较对照组（5.61±0.50）明显下降。第7天-第14天时，1组和2组SUVmax较第3天呈现持续下降趋势，且呈剂量效应关系（P < 0.05）。治疗后第3天-第14天，3组SUVmax较第0天显著上升，并在第7天达到峰值，后明显下降。同期3组SUVmax明显低于对照组SUVmax。HE染色显示近粒子处的肿瘤细胞变性坏死，坏死程度随剂量的增加而严重。3组可见坏死组织周围有大量炎性细胞浸润，而1组-2组炎性细胞浸润不明显。免疫组化显示治疗组bcl-2表达强度低于对照组，bax表达强度高于对照组（P < 0.05）。治疗组bcl-2/bax比值明显下调（P < 0.05）。凋亡基因的表达呈剂量效应关系。结论32P-CP-PLLA粒子持续照射可直接杀伤VX2肿瘤细胞从而抑制其葡萄糖代谢功能。远离粒子处虽可见存活肿瘤细胞，但凋亡基因表达明显异于对照组。32P-CP-PLLA粒子可通过电离辐射诱导bcl-2和bax基因参与VX2移植瘤细胞凋亡过程的调控，从而抑制肿瘤生长。

The pinhole SPECT for animal model of bone metastasis with SPC-A-1BM human pulmonary adenocarcinoma bone metastasis cell line

The study was to investigate the role of pinhole single photon emission computed tomography (SPECT), the human pulmonary adenocarcinoma bone-seeking metastasis cell line SPC-A-1BM was used. These cells form typical osteolytic bone metastases when inoculated into the arterial circulation of NIH-Beige-Nude-XD (BNX) mice via the left ventricle. In order to evaluate the irradiation impact of 99m Tc-MDP versus X-ray on cells growth, we used six groups of SPC-A-1BM cells in our imaging scheme and irradiated by various doses of 99mTc-MDP (37, 74, 111, 370, 740 MBq) and X-ray(40 kV. 2 mA, 6 s) respectively. The cell's number of each group was well recorded in different exposure time (4, 8, 12, 24, 48, 72, 96 hours). After that, SPC-A-1BM cells (1×106) were inoculated into the mice via left ventricle. We compared the results obtained with those different doses of 99mTc-MDP using pinhole SPECT and conventional X-ray skeletal surveys. The data show that the cell-survival number of 111 MBq group has insignificant difference with that of X-ray and the dose is adequate to have an ideal image. Besides, it is important that the chromosome of the cells in the group of 111 MBq showed no irradiation-related damages in our test. These results implied that 99mTc-MDP pinhole SPECT may provide another way other than conventional X-ray skeletal surveys in detecting bone metastasis of pulmonary adenocarcinoma in BNX mice.

Low vs. High Radioiodine Activity to Ablate the Thyroid after Thyroidectomy for Cancer: A Randomized Study

BackgroundRadioactive iodine is commonly administered following thyroidectomy for differentiated thyroid carcinoma to ablate the thyroid remnant. The optimal administered activity of radioiodine is unknown.Methodology/Principal FindingsAdult subjects (n = 160) diagnosed with papillary or follicular thyroid carcinoma were randomly allocated to receive either 1100 MBq (30 mCi) or 3700 MBq (100 mCi) activity of radioiodine (131I) following thyroidectomy. The study participants were prepared for ablation using thyroid hormone withdrawal. Ablation was considered successful when serum thyroglobulin concentration was less than 1 ng/mL and no uptake was present in 131I scan. Ablation was successful following one administration of radioiodine in 42 (52%; 95% CI, 41% to 63%) of the 81 evaluable study participants who received 1100 MBq, and in 43 (56%, 45% to 67%) of the 77 subjects who received 3700 MBq activity (P = .61). There was no difference between the groups in the numbers of repeat radioiodine treatments needed to complete ablation (P = .27). The higher activity was associated with more nausea and taste disturbances, and a longer stay in a radioprotected isolation unit. None of the participants died from thyroid cancer during a median follow up of 51 months; three subjects in the 3700 MBq group and none in the 1100 MBq group were diagnosed with distant metastases during follow-up. In a meta-analysis of four randomized studies that compared the 1100 and 3700 MBq activities, the 1100 MBq activity tended to be associated with a higher risk of unsuccessful ablation (relative risk 1.148, 95% CI 0.974 to 1.353, P = .10).Conclusions/SignificanceThe results provide no conclusive evidence that 3700 MBq activity is more effective for ablation of the thyroid remnant than 1100 MBq activity. The 3700 MBq activity is associated with more adverse effects.Trial RegistrationClinicalTrials.gov NCT00115895

A Comparison of 1850 (50 mCi) and 3700 MBq (100 mCi) 131-Iodine Administered Doses for Recombinant Thyrotropin-Stimulated Postoperative Thyroid Remnant Ablation in Differentiated Thyroid Cancer

Recently, a multicenter study in differentiated thyroid cancer (DTC) patients showed that 3700 MBq 131-iodine ((131)I) after recombinant human TSH (rhTSH) had a successful thyroid ablation rate similar to that obtained after thyroid hormone withdrawal. We investigated whether 1850 MBq (131)I had a similar successful rate to 3700 MBq in patients prepared with rhTSH. A total of 72 patients with DTC were randomly assigned to receive 1850 (group A, n = 36) or 3700 MBq (group B, n = 36) (131)I after rhTSH. One injection of 0.9 mg rhTSH was administered for 2 consecutive days; (131)I therapy was delivered 24 h after the last injection, followed by a posttherapy whole-body scan. Successful ablation was assessed 6-8 months later. Successful ablation (no visible uptake in the diagnostic whole-body scan after rhTSH stimulation) was achieved in 88.9% of group A and B patients. Basal and rhTSH-stimulated serum thyroglobulin was undetectable (<1 ng/ml) in 78.9% of group A and 66.6% of group B patients (P = 0.46). Similar rates of ablation were obtained in both groups also in patients with node metastases. Therapeutic (131)I activities of 1850 MBq are equally effective as 3700 MBq for thyroid ablation in DTC patients prepared with rhTSH, even in the presence of node metastases.

Complete Tumor Response Following Intratumoral 32P BioSilicon on Human Hepatocellular and Pancreatic Carcinoma Xenografts in Nude Mice

32P BioSilicon is a new, implantable, radiological medical device that comprises particles of highly pure silicon encapsulating 32phosphorus (32P) for the treatment of unresectable solid tumors. Prior to administration, the device particles are suspended in a formulant which provides an even suspension of the intended dose for implantation. The primary objective of this animal trial study was to investigate the effects of intratumoral injection of 32)P BioSilicon on human hepatocellular (HepG2) and pancreatic carcinoma (2119) xenografts implanted in nude mice (BALB/c). A secondary objective was the histopathologic examination of the tumor foci and surrounding tissue during the study. Cultured human carcinoma cells (HepG2 and 2119) were injected s.c. into the gluteal region of nude mice. When the implanted tumors were approximately 1 cm in diameter, 32P BioSilicon (0.5, 1.0, and 2.0 MBq) or formulant was injected into the tumors. Implanted tumor size was measured once a week for 10 weeks. At study termination, the tumor and surrounding normal tissue were collected and fixed in 10% formalin and processed for histopathologic analysis. 32P BioSilicon produced a reduction in HepG2 tumor volume when compared with formulant control, and complete response was observed among tumors in the 1.0 and 2.0 MBq treatment groups after week 8. There was also significant reduction in 2119 tumor volume in all treated groups, with the complete response rate of 67% in the 2.0 MBq group. 32P BioSilicon suppressed the growth of both human hepatocellular and pancreatic carcinoma xenografts implanted in nude mice and complete responses were also observed in tumors at higher radiation doses.

Chromic-P32 phosphate treatment of implanted pancreatic carcinoma: Mechanism involved

To study the effects of chromic-P32 phosphate (32P colloids) interstitial administration in Pc-3 implanted pancreatic carcinoma, and investigate its anticancer mechanism. Ninety-eight tumor bearing nude mice were killed at different time points after the injection of 32P colloids to the tumor core with observed radioactivity. The light microscopy, transmission electron microscopy (TEM) and immuno-histochemistry and flow cytometry were used to study the rates of tumor cell necrosis, proliferating cell nuclear antigen index, the micro vessel density (MVD). The changes of the biological response to the lymphatic transported 32P colloids in the inguinal lymph node (ILN) were dynamically observed, and the percentage of tumor cell apoptosis, and Apo2.7, caspase-3, Bcl-2, Bax-related gene expression were observed too. The half-life of effective medication is 13 d after injection of 32P colloids to the tumor stroma, in 1-6 groups, the tumor cell necrosis rates were 20%, 45%, 65%, 70%, 95% and 4%, respectively (F = 4.14-105.36, P<0.01). MVD were 38.5+/-4.0, 28.0+/-2.9, 17.0+/-2.9, 8.8+/-1.5, 5.7+/-2.3 and 65.0+/-5.2 (t = 11.9-26.1, P<0.01), respectively. Under TEM fairly differentiated Pc-3 cells were found. Thirty days after medication, tumors were shrunk and dried with scabs detached, and those in control group increased in size prominently with plenty of hypodermic blood vessels. In all animals the ILN were enlarged but in medicated animals they appeared later and smaller than those in control group. The extent of irradiative injury in ILN was positively correlated to the dosage of medication. Typical tumor cell apoptosis could be found under TEM in animals with intra-tumoral injection of low dosed 32P colloids. The peak of apoptosis occurred in 2.96 MBq group and 24 h after irradiation. In the course of irradiation-induced apoptosis, the value of Bcl-2/Bax was down regulated; Apo2.7 and caspase-3 protein expression were prominently increased dose dependently. 32P colloids intra-tumor injection having prominent anticancer effectiveness may reveal the ability of promoting cell differentiation. The low dose 32P colloids may induce human pancreatic carcinoma Pc-3 implanted tumor cell apoptosis; Apo2.7, caspase-3, Bcl-2 and Bax protein participated in regulating the process of irradiation induced cell apoptosis.

Lymphoscintigraphy in the Sentinel Lymph Node Technique for Breast Tumor: Value of Early and Late Images for the Learning Curve

As the performance of early (H+1 to H+4) and late (D1) lymphoscintigraphic images raises organizational problems in outpatient surgery for breast cancer, only early images are generally obtained. The present study evaluated whether two series of images are better than one and defined the advantages of both methodologies. One hundred and eighteen patients with infiltrating breast carcinoma (T_0, T₁ and T₂) were included in the study: 87 in group A (early and late images) and 31 in group B (only early images). All patients received two peritumoral injections of ^99mTc-sulfur colloid, 15–18 MBq (group A) and <15 MBq (group B). During the operation, the patent blue bye technique was associated with radioactivity detection. The two groups were comparable for histological type and tumor size and localization. Successful localization of sentinel nodes on early lymphoscintigraphic images was significantly greater for group B. The identification of a sentinel node focus on early lymphoscintigraphy increased by 10% during the study. Sentinel node detection by the isotopic method alone, or the two methods combined, was comparable for both groups. In radioactivity detection, the count rate for sentinel nodes versus background (contralateral breast) was similar for the two groups. During the learning phase, two series of images gave a definite advantage. Subsequently, lymphoscintigraphy performed at +2 h was sufficient (the results for the two groups became indistinguishable).