Varun Shandal

Evaluation of age-related changes in translocator protein (TSPO) in human brain using 11C-[R]-PK11195 PET

BackgroundWe studied the distribution and expression of translocator protein in the human brain using 11C-[R]-PK-11195 positron emission tomography (PK11195 PET) and evaluated age-related changes.MethodsA dynamic PK11195 PET scan was performed in 15 normal healthy adults (mean age: 29 ±8.5 years (range: 20 to 49); 7 males) and 10 children (mean age: 8.8 ±5.2 years (range: 1.2 to 17); 5 males), who were studied for potential neuroinflammation but showed no focally increased PK11195 binding. The PET images were evaluated by calculating standard uptake values and regional binding potential, based on a simplified reference region model, as well as with a voxel-wise analysis using statistical parametric mapping.ResultsPK11195 uptake in the brain is relatively low, compared with the subcortical structures, and symmetrical. The overall pattern of PK11195 distribution in the brain does not change with age. PK11195 uptake was lowest in the frontal-parietal-temporal cortex and highest in the pituitary gland, midbrain, thalamus, basal ganglia, occipital cortex, hippocampus and cerebellum, in descending order. White matter showed negligible PK11195 uptake. Overall, brain PK11195 uptake increased with age, with midbrain and thalamus showing relatively higher increases with age compared with other brain regions.ConclusionsThe brain shows low PK11195 uptake, which is lower in the cortex and cerebellum compared with subcortical structures, suggesting a low level of translocator protein expression. There is no hemispheric asymmetry in PK11195 uptake and the overall pattern of PK11195 distribution in the brain does not change with age. However, brain PK11195 uptake increases with age, with the thalamus and midbrain showing relatively higher increases compared with other brain regions. This increase in uptake suggests an age-related increase in translocator protein expression or the number of cells expressing these receptors or both.

Clinical applications of PET and PET/CT in pediatric malignancies

The common childhood cancers are leukemia, CNS tumors, lymphomas, soft-tissue tumors (such as rhabdomyosarcoma and fibrosarcoma), neuroblastoma, malignant bone tumors, germ cell tumors with neoplasms of gonads and hepatic tumors. Usually the conventional imaging modalities, such as x-ray, ultrasound, computed tomography (CT) and MRI, are being routinely used for the management of these pediatric malignancies. However, most of these modalities provide structural information and are lacking in functional/metabolic status of these malignancies. Recently, PET and PET/CT have emerged as a functional diagnostic imaging modality for the management of various cancers in adult population. Up to now most of the data published in the literature are on PET alone. PET used in conjunction with CT is useful as it provides an enhanced view of the anatomical details and the malignant focus then can be located with highest accuracy. PET and PET/CT has been found to be useful in, for example, CNS tumors, lymphomas, soft-tissue tumors, neuroblastoma, malignant bone tumors and germ cell tumors. PET/CT has a limited role in early diagnosis, however, it plays an important role in initial staging, treatment response evaluation and detection of metastatic disease in these cancers. Despite the fact that PET/CT has better diagnostic value when compared with conventional imaging, such as CT and MRI, in the management of many pediatric cancers, there are certain limitations. PET/CT has a limited role in detection of lesions smaller than 5 mm, well-differentiated tumors and tumors with low metabolic rate. Many infections and inflammation can lead to false-positive PET/CT results. In the present review we will discuss the various clinical indications of PET and PET/CT in pediatric cancers.

Role of FDG PET-CT in recurrent renal cell carcinoma.

AimTo determine the efficacy of positron emission tomography-computed tomography using F-18 fluoro-deoxy-glucose (F-18 FDG PET-CT) in diagnosing the recurrence of renal cell carcinoma (RCC) in patients treated earlier with partial or radical nephrectomy. MethodsWe assessed 63 patients with suspected recurrent RCC after nephrectomy. PET-CT findings were interpreted as positive if the focal area of FDG uptake in the abdomen or outside the abdomen was more than the surrounding background tissue. The final diagnosis of the recurrence of RCC was based on histological examination and/or clinical follow-up and conventional imaging modalities. ResultsA total of 103 PET-CT studies were done in these 63 patients, of which 63 studies were true positive, 30 studies were true negative, seven studies were false negative and remaining three studies were false positive. In 63 true-positive scans, PET-CT showed 109 lesions. Of these, 28 lesions were in the lungs, 21 lesions were at a locoregional site, 21 were in the bones, 12 in the retroperitoneal lymph nodes and 27 at other sites. The sensitivity, specificity and accuracy of PET-CT were 90, 91 and 90%, respectively. ConclusionOur results seem to confirm the useful role of PET-CT in the evaluation of post-surgical recurrence in patients who had undergone radical surgery for RCC.

Role of FDG-PET/CT in detection of recurrent disease in colorectal cancer.

BackgroundOne-third of patients with colorectal cancer (CRC) are likely to have a recurrence within the first 1–2 years. Conventional imaging modalities have limitations in detecting recurrent disease early. The purpose of this study was to assess the usefulness of fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) in the detection of recurrence in patients with CRCs. MethodsOne hundred and eighty-three patients, who were earlier treated with surgery and/or chemotherapy/radiotherapy, underwent 269 PET/CT studies for the detection of recurrence. The final diagnosis was made on the basis of histological analysis or clinical and imaging follow-up. ResultsThe sensitivity, specificity, accuracy, positive predictive value, and negative predictive value in detecting recurrent CRC using 18F-FDG-PET/CT were 87, 90, 88, 93, and 80%, respectively. PET/CT was found to have limitations in detecting microscopic disease and small-sized lesions. The common cause of false-positive PET/CT results was infective and inflammatory pathology in our setup. ConclusionPET/CT showed high sensitivity, specificity, and accuracy for the detection of recurrent disease in patients, who were earlier treated for CRC. PET/CT can be considered as a useful diagnostic tool in these patients.

Role of rhenium-188 tin colloid radiosynovectomy in patients with inflammatory knee joint conditions refractory to conventional therapy

AimTo evaluate the treatment response of rhenium-188 (188Re) tin colloid radiosynovectomy (188Re-RSV) in patients with inflammatory knee joint conditions refractory to conventional treatment. Materials and methodsSixty-one knee joints in 48 patients with chronic synovitis caused by various inflammatory knee joint diseases refractory to conventional therapy were included in this prospective study. All patients were assessed clinically for pain, tenderness, joint swelling, mobility, analgesic intake, and blood pool activity on bone scan. Different scores were assigned to all these parameters. RSV of knee joint was done using intra-articular injection of 555 MBq of 188Re tin colloid. Response was assessed at 3, 6, and 12 months using various clinical parameter scores and blood pool bone scan mentioned above and categorized as responders and nonresponders on the basis of change in percentage of cumulative scores. ResultsOf the 61 joints, 57 were responder and four were nonresponder at 3-month post-RSV. Out of 57 responders, seven had recurrence on further follow-up (three at 6 months and four at 12 months). There was a statistically significant reduction in clinical parameters cumulative scores at 3, 6, and 12 months when compared with baseline (P<0.0001) in responder group. Blood pool scinitgraphy also showed decrease in blood pool activity compared with the baseline. There was statistically significant association between the responder group and shorter duration of disease (P=0.011). Patients having normal or minor X-ray changes, little or no swelling, mild tenderness, and better mobility were independently associated with good response. Conclusion188Re tin colloid synovectomy is a useful treatment modality in patients with chronic inflammatory knee joint conditions refractory to conventional treatment. Patients with shorter duration of disease, normal or minor X-ray findings, little or no swelling, mild tenderness, and better mobility are better candidates for RSV.

FDG PET/CT evaluation of treatment response in patients with recurrent colorectal cancer.

Aim: To evaluate the treatment response in patients with recurrent colorectal cancer (CRC) using FDG PET/CT. Materials and Methods: A total of 32 recurrent CRC patients (21 males, 11 females; mean age, 52.8 years) were included in this retrospective study. All patients underwent a baseline and follow-up FDG PET/CT scans after chemotherapy. Of 32 patients, 23 patients had follow-up carcinoembryonic antigen (CEA) levels. Results: On qualitative analysis of baseline and follow-up FDG PET/CT studies, there were 20 nonresponders and 12 were responders. On quantitative analysis, there were 19 nonresponders and 13 were responders. In responders, baseline and follow-up mean SUVmax were 11.8 ± 10.1 and 3.7 ± 4.1, respectively (significant decrease, P = 0.001). Among nonresponders, baseline and follow-up mean SUVmax were 8.1 ± 5.2 and 14.1 ± 9.0, respectively (significant increase, P = 0.003). There was no association between response and different factors like age, sex, diagnosis, extent of the lesions, and number of lesions. Conclusion: FDG PET/CT appears to be useful modality in evaluating chemotherapy response and can differentiate responders from nonresponders in recurrent CRC patients.

Abnormal Brain Protein Synthesis in Language Areas of Children With Pervasive Developmental Disorder: A L-[1-11C]-Leucine PET Study

This study was performed to evaluate the cerebral protein synthesis rate of language brain regions in children with developmental delay with and without pervasive developmental disorder. The authors performed L-[1-11C]-leucine positron emission tomography (PET) on 8 developmental delay children with pervasive developmental disorder (mean age, 76.25 months) and 8 developmental delay children without pervasive developmental disorder (mean age, 77.63 months). They found a higher protein synthesis rate in developmental delay children with pervasive developmental disorder in the left posterior middle temporal region (P = .014). There was a significant correlation of the Gilliam Autism Rating Scale autism index score with the protein synthesis rate of the left posterior middle temporal region (r = .496, P = .05). In addition, significant asymmetric protein synthesis (right > left) was observed in developmental delay children without pervasive developmental disorder in the middle frontal and posterior middle temporal regions (P = .03 and P = .04, respectively). In conclusion, abnormal language area protein synthesis in developmentally delayed children may be related to pervasive symptoms.

Long-term outcome in children with intractable epilepsy showing bilateral diffuse cortical glucose hypometabolism pattern on positron emission tomography.

The objective of this study is to determine the long-term outcome of children with intractable epilepsy who have diffuse cortical hypometabolism on 2-deoxy-2-( 18 F)fluoro-D-glucose positron emission tomography (FDG-PET) scans. Seventeen children with intractable epilepsy showing bilateral, diffuse cortical hypometabolism on FDG-PET were followed up through telephone interview from 1 year 4 months to 11 years 4 months (mean: 5 years 7 months ± 2 years 1 month) after their PET scans. One child succumbed to Sanfilippo disease at age 20 years. Only 2 children were seizure free. Fifty percent had walking difficulties, 56.25% were not toilet trained, all had speech difficulties, 43.75% had behavioral problems, 37.5% had poor eye contact, 75% had socialization difficulties, and 87.5% attended special schools. Three children were found to have genetic causes, including a 4-MB deletion of the mitochondrial genome, MECP2 duplication, and Lafora disease. In conclusion, the long-term outcome in this patient population is poor, and they tend to suffer from genetic/neurodegenerative diseases.

Radionuclide Bone Imaging in Skeletal Tuberculosis

Tuberculosis (TB) is an ancient infective disease caused by Mycobacterium tuberculosis. The transmission is mainly through naso-oral route. It is one of the most common infectious diseases, and nearly 30 million people are affected all over the world. Of these, 95 % are found in developing countries, highlighting the environmental role in the development of the disease. However, after 1985, even affluent countries have been witnessing escalation in the incidence of TB by 10–30 % annually (Weaver and Lifeso 1984). By the beginning of the twentieth century, TB was the leading cause of death in Western society (Farer et al. 1979; Leff et al. 1979). Three related organisms, Mycobacterium tuberculosis, Mycobacterium africanum, and Mycobacterium bovis, are the causes of TB. Of these three organisms, Mycobacterium tuberculosis is the most common bacteria causing TB. Mycobacterium africanum is rarely found outside of northwestern Africa, and the disease due to Mycobacterium bovis is limited in developed countries by the widespread practice of pasteurization of milk (Reichman and Hershfield 1993).

Role of PET and PET/CT in Anticancer Drug Therapy Response Evaluation

Anti-cancer drug development is a major area of research. New imaging techniques provide a novel method for anti-cancer drug development and monitoring response to therapy by targeting functional metabolic activity at cellular level. The current assessment of the response to therapy in solid tumors based on measurement of the changes in tumor size have many limitations. Positron emission tomography (PET) has been used to measure changes in drug induced metabolism, cellular proliferation and tissue perfusion. Also, changes induced by immuno-modulating drugs such as apoptosis, telomere activity, growth factor levels and many more can be studied using specific radiolabelled PET tracers. Initially PET was used alone without any computed tomography (CT) or magnetic resonance imaging (MRI) hybridization. Since there are few limitations associated with PET alone, a novel combined PET/CT system has recently been built that improves the ability to correctly localize and interpret radiotracer uptake. Hybrid PET/CT scanners provide both the anatomical and functional aspects of the tissue. PET and PET/CT have been found to be very useful in various cancers. In the present study we have investigated role of PET/CT as a predictor of early response to chemotherapy in locally advanced breast cancer patients, lymphoma, pediatric cancer, lung cancer, etc. We have performed more than 14000 PET/CT at our institute. We have found that fluorine-18 fluoro-deoxy-glucose ( 18 F-FDG) PET/CT plays important role in early assessment of treatment response in various cancer patients. A positive PET/CT scans after the completion of therapy is a strong predictor of residual disease, whereas, a negative study is associated with complete remission in these patients.