核医学与放射治疗

Study background: Pyrazole moiety, being called as pharmacophore, plays an important role in many biologically active compounds and therefore represents an interesting template for combinatorial as well as medicinal chemistry. In addition pyrazoles are also used extensively as useful synthons in organic synthesis. These derivatives have wide spread biological activities such as anticancer, analgesic, anti-inflammatory, antimicrobial, antiviral, anticonvulsant, antihistaminic and anti-HIV. The recent success of pyrazole COX-2 inhibitor has further highlighted the importance of these heterocycles in medicinal chemistry.

Methodology: The steps included condensation followed by cyclization or MCR, either in a step-wise manner or in one pot has been achieved successfully to obtain this class of heterocycles under different conditions. Phosphorus oxychloride (POCl3 ), dimethyl formamide, acetamide and hydrazine are the most common reagents used for the synthesis of pyrazole appended heterocyclic skeletons. Results: The reaction schemes resulted in the synthesis of heterocyclic appended pyrazoles in potential yields under either simple reaction conditions or microwave irradiation.

Conclusion: These protocols provide convenient strategies to annelate different heterocyclic nuclei with widespread bioactive pyrazoles thereby extending the categories of heterocyclic systems. These strategies also provide valuable information for the further design of more active biological agents through various modifications and derivatizations.

Currently, many breast cancer patients with localized breast cancer undergo breast-conserving therapy, consisting of local excision followed by radiation therapy. Following radiation therapy, breast cancer cells are noted to undergo induction of autophagy, development of radioresistance, and enrichment of breast cancer stem cell subpopulations. It is hypothesized that inhibition of the cytoprotective autophagy that arises following radiation therapy increases radiosensitivity and confers longer relapse-free survival by eliminating tumor-initiating breast cancer stem cells. Therefore, we reviewed the controversial role of autophagy in breast cancer tumorigenesis and progression, autophagy induction by radiotherapy, and utilization of autophagy inhibitors to increase radiosensitivity of breast cancer and to target radioresistant breast cancer stem cells.

Primary intraosseous squamous cell carcinoma (PIOSCC) developing from a Keratocystic odontogenic tumor (KCOT) is a rare malignant neoplasm of the jaws. The incidence of carcinomas arising in odontogenic cysts are less. This article presents a case of PIOSCC of the mandible developing from a KCOT in a 35-year-old male patient.

Scintigraphy studies are very important in assessing the structure and function of thyroid gland whether it involves diagnosis or management. Thyroid scans usually conducted with TcO4-99m yield functional information valuable in the differential diagnosis of thyroid nodules. The most important role in management of nuclear medicine is pertinent to postoperative management of thyroid cancer patients.

Differentiated thyroid carcinoma (DTC), arising from thyroid follicular epithelial cells, accounts for the vast majority of thyroid cancers. Despite being well-differentiated, papillary thyroid cancers may be overtly or minimally invasive. They may invade lymphatics but are less likely to invade blood vessels. Iodine-131 (131I) is routinely used to image patients after thyroidectomy to assess the presence of residual thyroid tissue with or without metastasis. False positive 131I scans, showing the presence of 131I uptake in the absence of residual thyroid tissue or metastases can occur, although they are uncommon. Unless recognized as a false positive, 131I uptake may result in diagnostic error and lead to administration of an unnecessary higher therapeutic dose. We present a 55 year old female, histopathologically proven case of follicular variant of papillary carcinoma that underwent Total Thyroidectomy. Residual thyroid and whole body scan showed moderate residual thyroid tissue with abnormal 131I in right lung masquerading as right lung metastases. SPECTCT (single photon emission computed tomography – computed tomography) was incremental in localizing the site of 131I uptake to bronchiectatic changes. 131I diagnostic and post therapy scans are useful to risk stratify DTC patients’ so that amount of high dose 131I to be administered to patient can be estimated and judiciously used in their treatment.

Background: Cancer of the throat or larynx is one of the predominant cancer types in India and Intensity Mediated Radiation Therapy (IMRT) is the most crucial treatment regimen against the disease. We aimed to examine the effect of Circulating Endothelial Progenitor (CEP) cells in Laryngeal cancer patients undergoing radiation therapy.

Patients: Five Laryngeal cancer patients were selected for the work. All patients were suffering from Squamous Cell Carcinoma (SCC) of the glottis and admitted to the institute with CT1 and CT2 stage of tumor with no lymph node metastasis (CN0). After thorough check up the patients were subjected to conventional mononodal radiotherapy (IMRT), fractionated doses to the highest dose (1.8-2 Gy per fraction). Peripheral Blood Mononuclear Cells (PBMC) was isolated from all 5 patients and flow cytometric analysis (using anti CD 44 and CD309 monoclonal antibody) was performed before and after completion of the entire course.

Results: Results showed upregulation of the CEPs in all cases after exposure to radiotherapy. Additional immunofluorescence staining confirmed the rapid increase of these cells indicating a strong correlation between the exposure to ionizing radiation and stem cell expression in patients suffering from Glottic cancer.

Conclusion: Increase in the CEPs suggests that the tissue damage due to radiation exposure activate the stem cell niche and allures CEPs in the peripheral blood for angiogenesis. Further prospective assessments are warranted.

Needle tract seeding is a recognized complication of obtaining tissue of intraabdominal malignancy by percutaneous techniques. While the exact mechanism of needle tract seeding is still being hypothesized, the knowledge of this concept has led to guidelines avoiding such techniques in a resectable tumor especially tumors of hepatobiliary origin. Here we present a case of colonic carcinoma with a polypoidal soft tissue mass at the site of needle tract. The needle tract tumor could have probably indicated the poor response and should be considered as a poor prognostic factor. This technique should be avoided in resectable colonic tumors.

Locally advanced carcinoma of the uterine cervix is a major public health problem in developing countries. In spite of advancement in chemoradiation therapy, the outcome of locally advanced disease remains suboptimal. Newer diagnostic methods, treatment approaches and technology to evaluate the response needs to be evaluated in this condition. Some of the current issues of management of cervix cancer in developing countries are discussed in this present review. The direction of future research in imaging and neoadjuvant therapy are highlighted.

Objective: Non-traumatic intrinsic neuropathy of the brachial plexus (BP) could be because of focal or diffuse involvement. The purpose of this article is to focus on MR imaging spectrum and illustrate key features of a variety of pathologic entities based on review of 21 imaging studies. This paper highlights the detailed MR anatomy, the imaging techniques and the spectrum of MR imaging appearances of focal and diffuse form of non-traumatic intrinsic brachial neuropathy.

Materials and methods: We retrospectively reviewed 140 consecutive BP MR examinations performed at our institution over a period of four years from August 2006 to August 2010. We excluded cases of diverse clinical data including both traumatic and non-traumatic extrinsic compressive brachial neuropathies occuring along the course of the BP. Of 140 MR imaging studies of the BP, 75 were excluded and remaining 65 imaging studies were included for review. BP was assessed for the calibre, continuity, presence and distribution of signal changes (focal or diffuse) and focal masses.

Results: 21 of the 65 included imaging studies showed features of non-traumatic intrinsic BP neuropathy. The diagnosis was made on the basis of MR findings, electromyographic (EMG), clinical patient information and histopathological findings. The diagnosis included spectrum of neoplastic and non-neoplastic conditions like perineurioma, radiation plexitis, chronic inflammatory demyelinating polyneuropathy (CIDP) and hereditary motor sensory neuropathy (HMSN).

Radioiodine treatment, using iodine I-131, is one of the oldest clinical radionuclide therapy methods, and it is widely spread and currently used in the treatment of both thyreotoxicosis and thyroid cancer. The use of iodine may cause skin contaminations which may be a radiobiologic hazard and diagnostic problem.

Reported hazards in the radiopharmaceutical production of I-131 for therapy purposes are rare, but they might cause therapeutic approaches due to radioiodine uptake in the thyroid and destruction of thyroid tissue (mean beta range, 0.8 mm).

In this work a skin contamination causing a radioiodine thyroid uptake has been reported, together with thyroid cancer patients of receiving therapeutic doses of I-131 having skin contaminations from exudates.

These skin contaminations were quantificated, dose calculations were performed based on serial gamma detector and quantitative whole body gamma imaging, including SPECT/CT. For serial gamma imaging, thyroid retention and whole clearance after oral administration, rhTSH stimulation and thyroxin withdrawal give different results and therefore serial uptake estimates and time-activity curves are essential parameters for dose evaluation. Similarly, accidental subcutaneous administration for calculating thyroid uptake requires serial measurement as well.

In these patients, the skin contaminations did not cause any potential hazard to the environment nor to the hospital even though potential risks have been reported in the early days. Skin doses due to contaminations varied from 0.64 to 2.7 Gy. In the radiopharmaceutical production accidental skin contamination did not cause any harmful thyroid dose (80 mGy) due to rapid cleaning actions.

Quantitative gamma imaging together with activity calibrated detectors is the prerequisite for appropriate dose calculations when routes of administration differ from clinical routine.

Purpose: Incidents in radiation therapy occur due to the complex process, non-automated procedures, and miscommunication. We performed a prospective study to reduce the incidence rate during 4 years of external radiation therapy using incident-reporting system with multidisciplinary team (MDT) efforts.

Methods: Incidents from May 2009 to April 2013 were recorded, blame-free and voluntarily. The incidents involved errors which were unintended, whether they caused patient harm or not. Cause analysis of the incidents and interventions were performed through an MDT meeting in which all staff participated, including radiation oncologists, medical physicists, nurses, and radiation technologists. Our interventions included continuous feedback and improvements with minimized unnecessary stress.

Results: In total, 49 actual incidents among 2,350 radiation therapy courses were noted during the 4 years. The actual incidents occurred most frequently during treatment planning (74%, 36/49), followed by treatment delivery (20%, 10/49). Of the 49 actual incidents, 59%, 16%, 12%, 8%, 2%, 2% incidents were caused by failure to follow procedures or policies, incomplete knowledge, miscommunication, operation errors, work environment, and incorrect supervision, respectively. The actual incident rates, based on the number of treatment courses, were 4%, 2%, 1%, and 1% in the first, second, third, and fourth years, respectively. We found a significant decrease in the actual incident rate during the third and fourth years compared with the first year (p<0.01).

Conclusions: The frequency of incidents during radiation therapy was reduced using a voluntary incident reporting system and the efforts of a MDT.

Nuclear medicine and radiation therapy offer diagnostic and therapy services. These fields have grown in recent years by expanding coverage for the increasingly earlier treatment of serious diseases. In healthcare institutions, because of the risks, managers must provide continuing education at different levels in bioethics and biosafety according to their radioprotection program, and they must manage the legal exigencies concerning the health followup of the team members and patients. Health professionals work in these environments treating patients with different procedures and radionuclide schemes. The undesirable biological effects, such as stochastic and/or deterministic effects of ionizing radiation, may affect people's quality of life. The morbidity can vary from common problems, such as inflammation, to major unseen problems, such as mutations, with different risks of disease severity. Ultimately, death may occur after large accidental exposures. Managers need to consider psychological problems, side effects and iatrogenic diseases in patients and occupational diseases and accidents that can vary from small to large scale. Nuclear medicine and radiation therapy professionals need special education and training courses. The educational tools that are proposed here were based on Brazilian legislation for radiotherapy and knowledge of quality control, biosafety and bioethics. Good management and minimization of risk are necessary, and a high level of comprehension is required for the health professional staff member responsible for the health of individuals and an environment that guarantees success in both radiation therapy and nuclear medicine services. Some tools can be used to train professionals to minimize occupational risks and risks that threaten patient health. Checklists were prepared on a few topics concerning issues and recommendations regarding the containment of radionuclides and avoiding contact with reagents, waste and patient secretions and exposure during and after patient care.

Background and Aim: Liver directed therapy utilizing yttrium-90 microspheres represents a recently introduced in situ multidisciplinary cancer therapy that has caught the attention of many physicians faced with the challenges of treating these complex patients. Radioactive particle in capillary liver system were assessed through the in vivo test and the leakage to lung or other organ was defined. The concentration of Y-90 in liver tumor without leakage to the other organ was seen which has the important role in radioactive drug successes by radioimbolization method.
Method: Four different phases of Y 90 injection were performed in rabbits; 1. Preparation of Y-90 glasses microspheres, 2. Preservation, preparation and tumorization of the animal lab before and after drug injection, 3. Animal Angiography and injection of radioactive drug in animal liver, 4. Radionucleotide imaging of the animal; an assessment of stabilization of the radioactive particle in liver tumor. Early and late anterior and posterior injection of Y90 microspheres on rabbet showed. Yttrium 90 microspheres concentrated in liver, background, left and right lung were calculated. The mean ± SD was defined for the particle localization.
Result: The most Y90 microspheres were localized in late posterior view in rabbet and the less in background; 67.79 ± 19.9 and 13.65 ± 7.97 respectively. Considering the late posterior view the highest total count of particles were mostly seen in the liver and then in the background, 68804 and 12026 respectively. Early posterior injection of Y90 demonstrated the most particles were concentrated in liver 57.82 ± 17.66 and the smallest in the background 19.61 ± 6.63. Regarding early anterior injection, the most average number of the particles was reported 44.35 ± 13.10 in liver and the fewer particles were in background 17.93 ± 5.44. Concerning the late anterior view, the great total numbers of particles were concentrated in liver 1020 and the less in left and right lung with the number of 342. The average particles counts were calculated 79.33 ± 21.55 in the liver and 36.17 ± 8.7 in background.
Conclusion: Significantly higher doses of radiation can be delivered to a liver mass by intra-hepatic arterial administration of 90Y-microspheres and the most concentration of the particles were seen in the liver in comparison to the other organ. This treatment appears to be beneficial in non-respectable tumors with acceptable toxicity.

Purpose and Objective(s): To investigate the advantages of volumetric treatment planning in HDR brachytherapy for cervical carcinoma compared to standardized loading based on 2-D planning techniques.
Materials and Methods: Our institution uses volume-based 3-D planning for each tandem and ovoid (T&O) insertion for HDR brachytherapy in the treatment of advanced cervical carcinoma. Here, we attempt to define the benefits of this approach. We re-planned 48 CT-based treatment plans on 12 patients (treated in our facility between February, 2009 and February, 2010) using a commonly used 2-D standard HDR loading of the T&O. All patients had received 4 fractions of 6.5 Gy or 5 fractions of 5.5 Gy to point H or A. The following organs at risk (OARs) were contoured: rectum, bladder, sigmoid, and small bowel. Our customized planning approach required the adjustment of source dwell times and positions to keep doses to the OARs below 80% of the prescription dose. The standardized HDR planning, however, bases the loading time on the length of the tandem. The dwell time for each tandem source position is the same. The dwell time multipliers for the ovoids were 0.33, 0.665 and 1.0, proportionate to the 2 cm, 4 cm, and 6 cm tandem length, respectively. The dose to the highest 2 cc (D2cc) of the OARs were also determined and analyzed.
Results: There was a marked change in the value and location of the D2cc for all OARs from one HDR session to the next in both the standard and customized plans. When the data for the 48 plans were analyzed together, there were no significant differences between the customized plans and the standardized plans. However, when data for the individual plans were analyzed, 35% of the 2-D based plans did not meet our treatment planning objectives.
Conclusion: Using customized plans for HDR T&O brachytherapy did not always reduce the doses to the rectum, bladder, sigmoid, and small bowels compared to the standardized plans. The dose to the small bowel could be up to 15% higher than the dose to point H or A in the standard plans indicating that customized plans may be superior to the standardized ones for the treatment of patients where this dose is critical.