I-124 Imaging and Dosimetry

Although radioactive iodine imaging and therapy are one of the earliest applications of theranostics, there still remain a number of unresolved clinical questions as to the optimization of diagnostic techniques and dosimetry protocols. I-124 as a positron emission tomography (PET) radiotracer has the potential to improve the current clinical practice in the diagnosis and treatment of differentiated thyroid cancer. The higher sensitivity and spatial resolution of PET/computed tomography (CT) compared to standard gamma scintigraphy can aid in the detection of recurrent or metastatic disease and provide more accurate measurements of metabolic tumor volumes. However the complex decay schema of I-124 poses challenges to quantitative PET imaging. More prospective studies are needed to define optimal dosimetry protocols and to improve patientspecific treatment planning strategies, taking into account not only the absorbed dose to tumors but also methods to avoid toxicity to normal organs. A historical perspective of I-124 imaging and dosimetry as well as future concepts are discussed

Proliferative and Glycolytic Assessment of the Whole-Body Bone Marrow Compartment

Objective: Quantitative assessment of active bone marrow (BM) in vivo is yet to be well-defined. This study aims to compare total body BM volume estimations obtained from use of both18F-FLT PET/CT and 18F-FDG PET/CT in order to consolidate higher cellular proliferation rates with imaging the highly active red BM in pancreatic cancer. Methods: This phase I pilot study includes seven patients with pancreatic cancers who underwent both 18F-FLT and 18F-FDG imaging each acquired within a week’s duration. A CT-based classifier is used for segmenting bone into cortical and trabecular regions. The total BM volume is determined through statistical thresholding on PET activity found within the trabecular bone. Results: Results showed that 18F-FLT measures of red BM volume (RBV) were higher than those obtained from 18F-FDG (∆=89.21 ml). RBV obtained using 18F-FLT in males were found to have high correlation with measured weight (R2=0.61) and BMI (R2=0.70). The red BM fraction obtained from 18F-FLT was significantly different between males and females, with females showing much higher red bone matter within the trabecular bone (p<0.05). In contrast to 18F-FLT, 18F-FDG BM measurements showed that RBV was significantly different between males and females (p<0.05). Results also show that spinal activity SUV threshold for red BM segmentation is significantly different between 18F-FLT PET and 18F-FDG PET (p<0.05). Conclusion: By combining 18F-FLT-PET and 18F-FDG-PET, this study provides useful insights for in vivo BM estimation through its proliferative and glycolytic activitie

A Concise Atlas of Thyroid Cancer Next-Generation Sequencing Panel ThyroSeq v.2

The next-generation sequencing technology allows high out-put genomic analysis. An innovative assay in thyroid cancer, ThyroSeq® was developed for targeted mutation detection by next generation sequencing technology in fine needle aspiration and tissue samples. ThyroSeq v.2 next generation sequencing panel offers simultaneous sequencing and detection in >1000 hotspots of 14 thyroid cancer-related genes and for 42 types of gene fusions known to occur in thyroid cancer. ThyroSeq is being increasingly used to further narrow the indeterminate category defined by cytology for thyroid nodules. From a surgical perspective, genomic profiling also provides prognostic and predictive information and closely relates to determination of surgical strategy. Both the genomic analysis technology and the informatics for the cancer genome data base are rapidly developing. In this paper, we have gathered existing information on the thyroid cancer-related genes involved in the initiation and progression of thyroid cancer. Our goal is to assemble a glossary for the current ThyroSeq genomic panel that can help elucidate the role genomics play in thyroid cancer oncogenesis

Genomic Profiling of Thyroid Nodules: Current Role for ThyroSeq Next-Generation Sequencing on Clinical Decision-Making

In recent years there has been an increased awareness of the genetic alterations underlying both benign and malignant neoplasms of the thyroid. Next-generation sequencing (NGS) is an emerging technology that allows for rapid detection of a large number of genetic mutations in thyroid fine-needle aspiration (FNA) specimens. NGS for targeted mutational analysis in thyroid tumors has been proposed as a tool to assist in the diagnosis of thyroid nodules with indeterminate FNA cytology. Results of genomic testing of thyroid nodules and thyroid cancers could also have prognostic implications and play a role in determining optimal treatment strategies including targeted therapies. We provide a critical review of existing studies assessing the performance of the ThyroSeq NGS test for the diagnosis and management of patients with thyroid nodules with indeterminate cytopathology and discuss the applicability of findings from these studies to clinical practice. While there are early indications to suggest a possible utility of data obtained from NGS to aid in prognostication and therapeutic decisionmaking in thyroid cancer, we recommend judicious use and cautious interpretation of such molecular testing until results of ongoing clinical trials become available. Lastly, we discuss recommendations provided from clinical practice guidelines regarding the use of mutation detection via NGS in the diagnostic evaluation of thyroid nodules

A multimodality localization technique for radio-guided surgery

<p>Abstract</p> <p>Background</p> <p>Intraoperative localization of image or endoscopy-detected lesions occasionally pose surgical challenges due to the small lesion size and/or difficult anatomic exposure. Identification of such lesions can be facilitated using a hand-held gamma probe with utilization of Tc-99m macroaggregate albumen (MAA) localization technique. The radiopharmaceutical injection can be performed using ultrasound (US) or endoscopy guidance.</p> <p>Case presentations</p> <p>The clinical use of the Tc-99m MAA protocol gamma probe-guided surgery was discussed in three representative cases. Surgical indication was diagnostic exploration in two patients with suspicious lymphadenopathy, and determination of extent of surgical resection in a patient with polyposis. Lesion localization with 100 microcurie (3.7 MBq) Tc-99m MAA prior to surgical exploration resulted in definitive localization of lesions intraoperatively.</p> <p>Conclusion</p> <p>The use Tc-99m MAA deposition technique at the site of surgical target is a highly efficient radio-guided surgery technique with definitive impact on the success of surgical exploration in selected indications.</p

18F-FLT Positron Emission Tomography/Computed Tomography Imaging in Pancreatic Cancer: Determination of Tumor Proliferative Activity and Comparison with Glycolytic Activity as Measured by 18F-FDG Positron Emission Tomography/Computed Tomography Imaging

OBJECTIVE: This phase-I imaging study examined the imaging characteristic of 3’-deoxy-3’-((18)F)-fluorothymidine ((18)F-FLT) positron emission tomography (PET) in patients with pancreatic cancer and comparisons were made with ((18)F)-fluorodeoxyglucose ((18)F-FDG). The ultimate aim was to develop a molecular imaging tool that could better define the biologic characteristics of pancreas cancer, and to identify the patients who could potentially benefit from surgical resection who were deemed inoperable by conventional means of staging. METHODS: Six patients with newly diagnosed pancreatic cancer underwent a combined FLT and FDG computed tomography (CT) PET/CT imaging protocol. The FLT PET/CT scan was performed within 1 week of FDG PET/CT imaging. Tumor uptake of a tracer was determined and compared using various techniques; statistical thresholding (z score=2.5), and fixed standardized uptake value (SUV) thresholds of 1.4 and 2.5, and applying a threshold of 40% of maximum SUV (SUV(max)) and mean SUV (SUV(mean)). The correlation of functional tumor volumes (FTV) between (18)F-FDG and (18)F-FLT was assessed using linear regression analysis. RESULTS: It was found that there is a correlation in FTV due to metabolic and proliferation activity when using a threshold of SUV 2.5 for FDG and 1.4 for FLT (r=0.698, p=ns), but a better correlation was obtained when using SUV of 2.5 for both tracers (r=0.698, p=ns). The z score thresholding (z=2.5) method showed lower correlation between the FTVs (r=0.698, p=ns) of FDG and FLT PET. CONCLUSION: Different tumor segmentation techniques yielded varying degrees of correlation in FTV between FLT and FDG-PET images. FLT imaging may have a different meaning in determining tumor biology and prognosis

90Y-DOTA-CHS Microspheres for Live Radiomicrosphere Therapy: Preliminary In Vivo Lung Radiochemical Stability Studies

Chitosan (CHS) is used to prepare microspheres of 31 ± 8 µm size. Surface modification with p-SCN-Bn-DOTA was performed. A maximum 90Y capacity was found to be 12.1 ± 4.4 µCi/particle. The best obtained labeling yield was 87.7 ± 0.6%. More than 90% in vitro stability was found. Particle in vitro degradation half-life in PBS was found to be greater than 21 days. In vivo studies with 90Y-DOTA-CHS showed more than 95% of the injected activity (decay corrected) in the lungs 24 hours after tail vein administration. 90Y-DOTA-CHS in vivo label stability was superior to resin microspheres. The addition of p-SCN-Bn-DOTA served as a radioprotectant for bone marrow as the 5% 90Y released, during the first 24 hours, was quickly eliminated via urine

68Ga-NOTA-CHSg and 99mTc-CHSg Labeled Microspheres for Lung Perfusion and Liver Radiomicrospheres Therapy Planning

Fast biodegradable (12 h \u3c half-life \u3c 48 h) radioactive labeled microspheres are needed for PET and SPECT lung perfusion and radiomicrosphere therapy planning. An emulsion method was used to create 30.1 ±4.8 μm size range microspheres with biodegradable Chitosan glycol (CHSg). Microspheres were characterized and labeled with or as an alternative to MAA in perfusion PET and SPECT studies. Surface decoration of CHSg microspheres with p-SCN-Bn-NOTA was performed to increase   in vivo stability. was labeled directly to the CHSg microspheres. Labeling yield and in vitro radiochemical stability were evaluated. In vitro CHSg microsphere degradation half-life was ~24 hours in porcine blood. Labeled microspheres were injected into Sprague Dawley rats and biodistribution was determined after 2 and 4 hours. Both -CHSg and -NOTA-CHSg were quickly allocated in the lungs after injection. -CHSg showed 91.6 ± 6.5% and 83.2 ± 4.1% of the decay corrected injected activity remaining in the lungs after 2 and 4 hours, respectively. For the obtained -NOTA-CHSg microspheres, lung allocation was very high with 98.9 ± 0.2% and 95.6 ± 0.9% after 2 and 4 hours, respectively. The addition of p-SCN-Bn-NOTA acts as a radioprotectant eliminating the released activity from the lungs to the bladder protecting the other organs

PET probe-guided surgery: applications and clinical protocol

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