Radioimmunotherapy (RIT) in Brain Tumors / 대한핵의학회잡지

Annually, the incidence of brain tumors has slightly increased and also the patient prognosis is still disappointing, especially for high-grade neoplasms. So, researchers seek methods to improve therapeutic index as a critical aim of treatment. One of these new challenging methods is radioimmunotherapy (RIT) that involves recruiting a coupling of radionuclide component with monoclonal antibody (mAb) which are targeted against cell surface tumor–related antigens or antigens of cells within the tumor microenvironment. In the context of cancer care, precision medicine is exemplified by RIT; precision medicine can offer a tailored treatment to meet the needs for treatment of brain tumors. This review aims to discuss the molecular targets used in radioimmunotherapy of brain tumors, available and future radioimmunopharmaceutics, clinical trials of radioimmunotherapy in brain neoplasms, and eventually, conclusion and future perspective of application of radioimmunotherapy in neurooncology cancer care.

Radioimmunotherapy (RIT) in Brain Tumors / 대한핵의학회잡지

Annually, the incidence of brain tumors has slightly increased and also the patient prognosis is still disappointing, especially for high-grade neoplasms. So, researchers seek methods to improve therapeutic index as a critical aim of treatment. One of these new challenging methods is radioimmunotherapy (RIT) that involves recruiting a coupling of radionuclide component with monoclonal antibody (mAb) which are targeted against cell surface tumor–related antigens or antigens of cells within the tumor microenvironment. In the context of cancer care, precision medicine is exemplified by RIT; precision medicine can offer a tailored treatment to meet the needs for treatment of brain tumors. This review aims to discuss the molecular targets used in radioimmunotherapy of brain tumors, available and future radioimmunopharmaceutics, clinical trials of radioimmunotherapy in brain neoplasms, and eventually, conclusion and future perspective of application of radioimmunotherapy in neurooncology cancer care.

Radiation-induced myocardial perfusion abnormalities in breast cancer patients following external beam radiation therapy

Objective[s]: radiation therapy for breast cancer can induce myocardial capillary injury and increase cardiovascular morbidity and mortality. A prospective cohort was conducted to study the prevalence of myocardial perfusion abnormalities following radiation therapy of left-sided breast cancer patients as compared to those with right-sided cancer

Methods: to minimize potential confounding factors, only those patients with low 10-year risk of coronary artery disease [based on Framingham risk scoring] were included. All patients were initially treated by modified radical mastectomy and then were managed by postoperative 3D Conformal Radiation Therapy [CRT] to the surgical bed with an additional 1-cm margin, delivered by 46-50 Gy [in 2 Gy daily fractions] over a 5-week course. The same dose-adjusted chemotherapy regimen [including anthracyclines, cyclophosphamide and taxol] was given to all patients. Six months after radiation therapy, all patients underwent cardiac SPECT for the evaluation of myocardial perfusion

Results: a total of 71 patients with a mean age of 45.3 +/- 7.2 years [35 patients with leftsided breast cancer [exposed] and 36 patients with right-sided cancer [controls]] were enrolled. Dose-volume histogram [DVH] [showing the percentage of the heart exposed to >50% of radiation] was significantly higher in patients with left-sided breast cancer. Visual interpretation detected perfusion abnormalities in 42.9% of cases and 16.7% of controls [P=0.02, Odds ratio=1.46]. In semiquantitative segmental analysis, only apical [28.6% versus 8.3%, P=0.03] and anterolateral [17.1% versus 2.8%, P=0.049] walls showed significantly reduced myocardial perfusion in the exposed group. Summed Stress Score [SSS] of>3 was observed in twelve cases [34.3%], while in five of the controls [13.9%],[Odds ratio=1.3]. There was no significant difference between the groups regarding left ventricular ejection fraction

Conclusion: the risk of radiation induced myocardial perfusion abnormality in patients treated with CRT on the left hemi thorax is not low. It is reasonable to minimize the volume of the heart being in the field of radiation employing didactic radiation planning techniques. Also it is advisable to screen these patients with MPI-SPECT, even if they are clinically asymptomatic, as early diagnosis and treatment of silent ischemia may change the outcome

Effectiveness and complications of [153]Sm-EDTMP in palliative treatment of diffuse skeletal metastases

The aim of the present study was to evaluate the efficacy and safety profile of bone palliative therapy following administration of [153]Sm-EDTMP in patients with intractable metastatic bone pain. Sixteen patients [9 male, 7 female] aged 29-80 years [57.3 +/- 16.7 years] with severe metastasis-related bone pain resistant to analgesic medications were enrolled in the study. All patients having multiple bone metastases, positive bone scans, and estimated life expectancy of more than 2-3 months were entered the study. All patients received intravenous injection of 1.5 mCi [56 MBq]/kg of [153]Sm-EDTMP. Four subscales for the intensity of pain were recorded: one as the present pain score [PPS] and the other three as maximum pain score [Max PS], minimum pain score [Min PS] and average pain score [APS] over the last 24 hours. Also the mean value of these 4 subscales was calculated as the mean total pain score [MTPS]. The pain mental interference [PMI] was also assessed in 9 separate. Seven patients with breast cancer [43.75%], seven with prostate cancer [43.75%], one with papillary thyroid carcinoma [6.25%] and one with malignant paraganglioma [6.25%] were included in the study. A significant response to therapy, i.e. 2-point reduction in pain score and/or remarkable reduction [>/=25%] in the equivalent narcotic dose, was observed in 11 out of 16 patients [68.7%] by the 2nd week and in 12 patients [75%] by the 8[th] week. Regarding the palliative response to treatment and equivalent narcotic dose reduction, no significant difference between two major types of underlying malignancies [breast and prostate cancer] was found. There was no significant difference regarding response to therapy between two genders and among different age groups. The severity of bone marrow suppression was graded

[99m]tc-ubiquicidin [29-41], a promising radiopharmaceutical to differentiate orthopedic implant infections from sterile inflammation

Ubiquicidin [UBI] [29-41] is a synthetic cationic antimicrobial peptide that preferentially binds to bacterial cell membrane at the site of infection. We aimed to assess diagnostic value of [99m]Tc-UBI [29-41] as a radiopharmaceutical in differentiation of bacterial infection from sterile inflammation in suspected orthopedic implants. Nine patients suspected for orthopedic implant infection, all males with the mean age of 41.6 +/- 20.9 years, were studied. A dose of 10 MBq/Kg [range: 555-740 MBq] [99m]Tc-UBI [29-41] was injected intravenously. A dynamic study followed by static whole body imaging at 30, 60 and 120 min post-radiotracer injection was acquired. Periprosthetic tissue culture was considered the closest test to a gold standard for diagnosing infections and scintigraphic scans were categorized as true- or false-positive and true- or false-negative, considering the bacterial culture as the gold standard. No adverse reaction was observed during or after the radiotracer injection days. There were five true positive, four true negative and no false positive and false negative scans. Sensitivity, specificity, positive predictive value [PPV] and negative predictive value [NPV] were all calculated as 100%. We found a high diagnostic accuracy for [99m]Tc-UBI [29-41] scintigraphy in differentiation of bacterial infection from sterile inflammation in suspected orthopedic implants. Therefore, [99m]Tc-UBI [29-41] scintigraphy might be potentially recommended as a safe and promising imaging modality in these settings. However, further studies on a larger number of patients and different pathologies are still needed

Evaluation of myocardial perfusion and function after kidney ? transplantation by Gated SPECT myocardial perfusion scintigraphy

The aim of this study was to evaluate the effect of successful kidney transplantation [KT] on myocardial perfusion and left ventricular function by both qualitative [visual] interpretation and semiquantitative parameters, using myocardial perfusion scintigraphy with gated-single photon emission computed tomography [gated-SPECT] in patients suffering from end-stage renal disease. From a total of 38 patients who were candidates of KT, twenty-six patients [16 female, 10 male, mean age: 47.5 yr, range: 24-64 yr] who had successful KT were included. Myocardial perfusion scintigraphy was performed by Gated Single Photon Emission Computed Tomography [Gated-SPECT] method, before and after surgery [mean: 24 months]. Perfusion and function status was evaluated by qualitative and semiquantitative parameters. Our data showed qualitative evidence of perfusion and functional abnormality in pre-transplant scans as follows: Abnormal perfusion in left anterior descending [LAD], left circumflex [LCX] and right coronary artery [RCA] territories in 42.5%, 53.8% and 65.4% of cases, respectively; dilation in 57.7% and inhomogenity of uptake in 53.8% of cases. However no statistically significant change was noted after transplantation, i.e. p value for all semiquantitative values including summed stress score [SSS], summed rest score [SRS] and summed difference score [SDS], summed motion score [SMS], summed thickening score [STS], ejection fraction [EF], end diastolic volume [EDV], end systolic volume [ESV], and stroke volume [SV] was greater than 0.05. Renal transplantation may not have considerable long term effect on myocardial perfusion and function in patients with chronic renal failure. This could be due to either non-reversible myocardial changes or continuing effect of degrading factors on the myocardium

Additive clinical value of bone scintigraphy in patients with malignant tumors with absence of localized bone pain: a report on most common sex-related cancers

Almost all malignant tumors have the potential to eventually produce bone metastasis. The aim of the current study was to report the distribution pattern and imaging characteristics of bone metastases detected by conventional whole body bone scintigraphy in patients with different types of malignancies and to assess their relationship with the complaint of bone pain. As a cross-sectional study, 146 consecutive patients with histologically proven cancer who were referred for the assessment of possible bone metastatic involvement were investigated by 99mTc-Methylene Diphosphonate [MDP] whole body scintigraphy. A total of 146 patients [79 male and 67 female; mean age: 59.59 +/- 11.95] were enrolled, of which 71 [48.6%] patients had prostate cancer, 61 [41.8%] breast cancer, 6 [4.1%] gastric malignancy, and 8 [5.5%] miscellaneous cancers. The most frequent sites of bone metastases [vertebrae, pelvis and sternum] demonstrated more intense radiotracer uptake. Most of patients [58.5%] with bone metastasis due to breast cancer reported no localized bone pain. Also in the subgroup with prostate cancer, no significant association was noted between the site of bone metastases and location of the pain perception in most of the skeletal zones. Bone scintigraphy [by determining the specific pattern of bone metastases in different tumor types] may help physicians provide better care for patients who suffered from metastatic cancer. On the other hand, in view of the fact that no reliance can be placed on clinical symptoms and the patients' report of bone pain, bone scintigraphic data can be included in the follow-up evaluation of patients suspected to have bone metastasis, even in the absence of bone pain

study of demographic and clinical features of patients referred to the nuclear medicine department of a military hospital for myocardial perfusion scintigraphy

It seems that demographic and clinical features of patients referred for myocardial perfusion scintigraphy [MPS] is different among populations and healthcare settings. The purpose of the current study is to evaluate the clinical features and risk factors of patients referred for myocardial perfusion scintigraphy to a military hospital. As a cross-sectional study, the clinical and laboratory data of all patients who were referred for MPS were recorded. MPS was performed using [99m]Tc-Sestamibi or Thallium-201 [Tl-201] as the radiotracer. From March 2005 to March 2006, the data of 1392 consecutive patients were recorded. The mean age of the patients was 55.3 +/- 14.8 years. 45.6% of the patients had no major risk factor, while 38.5% had one and 15.9% had two risk factors. Hypertension was the most common risk factor, while cigarette smoking was reported by eight percent of the patients. The method of stress protocol was dipyridamole infusion in 69.2%, Treadmill exercise test in 28.4% and dobutamine infusion in 2.4% of the cases. The sensitivity, specificity, positive predictive value, negative predictive value and overall accuracy of MPS in detection of angiographically positive CAD were 88.5%, 71.4%, 94.3%, 46.8% and 75.3%, respectively. In our population hypertension is the most frequent risk factor, so extensive social programs should be implemented aiming at controlling this variable, in order to prevent its possible cardiac complications. Cigarette smoking is less common than general population, which could be due to social characteristics of the target community and their beliefs, so this distinctiveness should be well defined and promoted. The differences in the pattern of cardiovascular symptoms and risk factors can be considered as indirect evidences to the fact that the pattern of referral for MPS in our country is significantly different from those in developed countries, a fact that warrants further evaluation in order to confirm its appropriateness based on the validated international guidelines

Post-thoracotomy pain and pulmonary function - comparison of intermittent intercostal- bupivacaine vs intravenous pethidine

In a prospective, observer-blind study, 50 patients scheduled for posterolateral thoracotomy were investigated to compare the effects of intermittent intercostal extrapleural bupivacaine [n= 25] and intravenous pethidine [n = 25] on post-thoracotomy pain and pulmonary function. The severity of chest pain [objectified by the use 5- point scale of Prince Henry] and changes in spirometric values [forced vital capacity [FVC], forced expired volume in 1 s [FEV1] and FEV1/FVC] were monitored during the first three postoperative days. Because intravenous pethidine was used to supplement pain relief in the patients who received intercostal analgesia, total pethidine used was compared to that administered to patients in the intravenous pethidine group. There were no statistical significant differences regarding patient demographics in both groups. No complications occurred. There was no significant difference between mean pain scores in the first postoperative day, but in the second and third postoperative days and also in the whole first 72 post-operative hours, pain scores were significantly higher in the intravenous group than the intercostal group. The postoperative decrease in FVC and FEVI was significantly less with intercostal bupivacaine compared with the intravenous pethidine. There was no significant intergroup difference in the post-to pre-operative FEVI/FVC ratio. The total amount of the pethidine received by the patients was significantly higher in the intravenous group than the intercostal group. Intermittent intercostal nerve block with bupivacaine appears to be a promising, safe and reliable technique in the management of post-thoracotomy pain. Use of intercostal bupivacaine could significantly reduce or even eliminate the postoperative need for systemic narcotics

Post-thoracotomy analgesia comparison epidural fentanyl to intravenous pethidine

To evaluate the efficacy of post-thoracotomy analgesia with intermittent epidural fentanyl. 50 patients were allocated randomly into 2 groups. The first group received intermittent epidural fentanyl and the second group received intermittent intravenous analgesia using pethidine. The variables studied were: pain score; total amount of additional intravenous opioid analgesia, and ventilatory function parameters [forced vital capacity [FVC], forced expiratory volume in the first second [FEV[1]] and FEV[1]/FVC ratio]. In the first postoperative day, pain scores were higher in the epidural group [P = 0.034], but there was no significant difference between mean pain scores in the second and third days [P = 0.61, P = 0.15, respectively]. On all three days, significantly more additional analgesics were required in the epidural group. A difference was found between both groups in the post- to pre-operative FEV[1], FVC and FEV[1]/FVC ratios, with the better preservation of the ventilatory function in the epidural group [P= 0.001, 0.013, O.0001, respectively]. The analgesic effect of intermittent epidural fentanyl is not adequate, and postoperative pain relief has not any significant advantage over the more easily-applied intravenous analgesia. However, better preservation of ventilatory function makes epidural fentanyl a useful adjunct analgesia in reduction of post-thoracotomy pulmonary complications

[ first experience of stem cell labeling in iran using 111In- oxine]

The field of stem cell biology and regenerative medicine is rapidly moving toward translation to clinical practice. Stem cell therapy seems to be a new treatment option for some diseases. So, tracking the distribution of stem cells is crucial to their therapeutic use. Based on this fact we labeled human mesenchymal stem cells [MSCs] with 111In-oxine for the first time in our country. The aim of this study was to investigate the possibility of stem cell labeling in Iran. In addition the researchers assessed the cell viability, specific activity and labeling efficiency after labeling. After culturing mesenchymal stem cells [MSCs], for radio-labeling, the sample [which contained 1x106MSCs] were mixed, and suspended with 50 micro Ci 111In-oxine, and then incubated for 20 min at the room temperature. The cells were then washed with normal saline twice to remove the free 111In. The labeling efficiency, specific activity and cell viability was 70.6%, 31.70 micro Ci/106 and 100%, respectively. It seems that, this method is practical and easily applicable with acceptable efficiency and specific activity in our laboratory settings using pharmaceutical produced in Iran