Incidentally detected follicular thyroid carcinoma mimicking parathyroid adenoma on Tc-99m MIBI scan: A case report.

RATIONALE: Primary hyperparathyroidism, though relatively prevalent among endocrine disorders, affecting 1% of the general population, often presents diagnostic challenges. Given its potential to precipitate severe complications including nephrolithiasis and fractures, timely diagnosis, and effective management are crucial. PATIENT CONCERNS: A 38-year-old woman with hypercalcemia was referred to the Department of Nuclear Medicine for a Tc-99m MIBI scan. DIAGNOSES: Tc-99m MIBI scan showed focal increased uptake in the left thyroid gland area, initially suggesting a parathyroid adenoma. Further examination using SPECT/CT revealed a nodular lesion within the left thyroid gland showing high Tc-99m MIBI uptake. INTERVENTIONS: Left thyroid lumpectomy confirmed the lesion as follicular thyroid carcinoma. On the second Tc-99m MIBI scan conducted after total thyroidectomy, a parathyroid adenoma was eventually detected in the right lower area, enabling the subsequent appropriate treatment, a right lower parathyroidectomy. OUTCOMES: Thirteen days after the parathyroidectomy, serum levels of total calcium and parathyroid hormone returned to normal. Furthermore, bone mineral density evaluated using DEXA remained within the expected range for her age even after 14 months. LESSONS: When interpreting the Tc-99m MIBI scan, it is essential to keep in mind that various tumors rich in mitochondria, such as thyroid carcinoma, could show a high uptake of Tc-99m MIBI.

Serial Migration of Iatrogenic Microembolus on 18 F-FDG PET/CT Images.

ABSTRACT: A 51-year-old woman who had a history of partial nephrectomy underwent an 18 F-FDG PET/CT image for a routine health checkup. Focal intense FDG avidity without any anatomical correlation on CT was detected in the lung. On the delayed image after 20 minutes, the focal activity migrated to a more peripheral portion. An iatrogenic microembolus is a rare but crucial false-positive finding that nuclear physicians should be aware of. Our case emphasizes the importance of meticulous FDG injection and cautious interpretation. In addition, delayed PET/CT imaging through wet reading can aid in diagnosing and help prevent unnecessary investigations.

Prediction of leg-length discrepancy in pediatric femoral shaft fracture using bone SPECT/CT: A case report.

RATIONALE: Children's bones are in the process of growing in both length and width. Therefore, evaluating whether fractures affect the growth plate or not is very crucial. However, even in cases of lower limb fractures where the growth plate remains unaffected, overgrowth or shortening of the affected limb are encountered. PATIENT CONCERNS: An 11-year-old boy was admitted to the emergency department after a passenger car accident. DIAGNOSES: A comminuted fracture of the right femoral shaft was diagnosed by X-ray image. INTERVENTIONS: Closed reduction and internal fixation were performed using intramedullary titanium elastic nails. Six months after the operation, bone union was achieved and the nails were removed. OUTCOMES: Nine months after nail removal, the right leg was unexpectedly noticed 5 mm shorter than the left one. On the initial and follow-up bone single-photon emission computed tomography/computed tomography images with a 9-month interval, radioactivity of growth plate in the right proximal femur was much lower than that of the left femur, suggesting a further increasing of leg-length discrepancy (LLD) in the future. As we expected, LLD had progressively increased up to 20 mm. Epiphysiodesis was finally decided for the left distal femur. Twenty-two months after the length equalization operation, LLD decreased to 5 mm. LESSONS: This case emphasizes that quantitative analysis of growth plate activity using bone single-photon emission computed tomography/computed tomography could predict LLD and help us decide when and which limb should be operated on for pediatric patients with lower limb fractures.

Incidental accumulation of Technetium-99m pertechnetate in subacute cerebral infarction: A case report.

BACKGROUND: When interpreting nuclear medicine images, unexpected findings are sometimes encountered. Recognizing these findings and determining the mechanism of their occurrence could have a significant impact on early diagnosis of critical diseases and the appropriate management of patients. CASE SUMMARY: A 59-year-old man was admitted to the emergency room due to left hemiparesis, left hemifacial palsy, and mild dysarthria. After 2 wk of hospitalization, the patient complained of dry eyes and mouth. Thus, salivary scintigraphy was performed to evaluate the functional status of his salivary glands. Incidental accumulation in the right frontoparietal area was found on salivary scintigraphy. Fluid-attenuated inversion recovery phase magnetic resonance (FLAIR phase MR) image showed diffuse high signal intensity in the same area. Anterior and posterior horns of the right lateral ventricle were obliterated and the midline was slightly shifted to the left side due to right frontoparietal swelling. On salivary scintigraphy, Tc-99m pertechnetate was incidentally accumulated in a subacute cerebral infarction lesion. Two years after the diagnosis of acute infarction, the second series of salivary scintigraphy showed no abnormal activity in the brain. FLAIR phase MR image also demonstrated markedly decreased high signal intensity in the previous infarction lesion without evidence of swelling indicating chronic cerebral infarction. CONCLUSION: This case highlights that Tc-99m pertechnetate could accumulate in a subacute cerebral infarction lesion. The mechanism of an unexpected uptake of Tc-99m pertechnetate in unusual sites should be evaluated and kept in mind for better interpretation.

Clinical and metabolic parameters for predicting disease progression of gallbladder adenocarcinoma.

OBJECTIVE: This study aimed to identify reliable predictors of disease progression in patients with gallbladder (GB) adenocarcinoma. PATIENTS AND METHODS: A total of 54 patients with GB adenocarcinoma underwent preoperative F-18 fluorodeoxyglucose (FDG) PET/CT. Age, sex, clinical stage, and pathologic differentiation were collected. Tumor size and PET parameters such as SUVmax, SUVmean, SUVpeak, metabolic tumor volume (MTV), and total lesion glycolysis were measured. Univariate and multivariate logistic regression analyses were performed to determine the utility of clinical values and PET parameters. Pearson bivariate correlation was used to evaluate the association between progression-free survival (PFS) and various parameters. RESULTS: No recurrence was found in 15 of 54 patients, while six showed recurrence and another 33 manifested disease progression. There were significant differences in size, stage, pathologic differentiation, and PET parameters between the groups with and without recurrence/progression. However, there was no difference in those parameters between the groups with recurrence and progression. The average PFS of the groups with no recurrence, recurrence, and progression groups was 33.1, 17.1, and 5.0 months, respectively. In univariate analysis, age, sex, clinical stage, pathologic differentiation, size, and PET parameters were correlated with PFS. In multivariate analysis, only clinical stage and MTV were statistically significant and MTV showed the highest odds ratio. Pearson correlation coefficients showed moderate negative correlations between PFS and clinical stage or MTV. CONCLUSION: In GB adenocarcinoma, clinical stage and MTV are the most powerful parameters for predicting recurrence and disease progression. Based on clinical stage, MTV will represent a strong prognostic predictor.

Atypical sarcoid reaction mimicking recurrence on F-18 FDG PET/CT in a patient with breast malignancy.

Malignancy may lead to sarcoidosis, which is referred to as sarcoid reaction. This reaction is believed to be a host immune response to the release of soluble antigens from cancer cells. Studies have shown strong 2'-deoxy-2'-[F-18]fluoro-D-glucose (F-18 FDG) uptake in sarcoid reaction and in true sarcoidosis. Therefore, in patients with malignancy, sarcoid reactions can mimic metastasis or recurrence on F-18 FDG positron emission tomography/computed tomography (PET/CT). Herein, we report the case of a 58-year-old woman with a history of left breast cancer whose FDG PET/CT evaluated at 3 months after adjuvant chemotherapy presented hypermetabolic lymphadenopathy in the right supraclavicular and right mediastinal areas. We interpreted these as metastases because the involved lymph nodes were intensely hypermetabolic and appeared newly. Pathologic evaluation of the excised lymph node revealed noncaseating chronic granulomas without malignant cells, indicating a sarcoid reaction. After appropriate steroid therapy, both the size and metabolic activity of the lymphadenopathy substantially decreased. Most sarcoid reactions present as bilateral hilar and peribronchial lymphadenopathies. Our patient presents an atypical example that a sarcoid reaction can also present in a unilateral pattern, making its diagnosis challenging. When interpreting FDG PET/CT images, considering that the sarcoid reaction pattern can vary is crucial.

Usefulness of cyclic thermal therapy and red blood cell scintigraphy in patients with chemotherapy-induced peripheral neuropathy.

BACKGROUND: Pharmacological and non-pharmacological therapies have been used to treat patients with chemotherapy-induced peripheral neuropathy (CIPN). However, the effect of therapies in cancer patients has yet to be investigated comprehensively. We hypothesized that cyclic thermal therapy would improve blood flow and microcirculation and improve the symptoms driven by CIPN. METHODS: The criteria of assessment were blood volume in region of interest (ROI) in the images, and European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy 20 questionnaire scores. The blood volume was quantified by using red blood cell (RBC) scintigraphy. All patients were treated 10 times during 10 days. The thermal stimulations, between 15° and 41°, were repeatedly delivered to the patient's hands. RESULTS: The total score of the questionnaires, the score of questions related to the upper limbs, the score of questions closely related to the upper limbs, and the score excluding the upper limbs questions was decreased. The blood volume was decreased, and the variance of blood volume was decreased. During cooling stimulation, the blood volume was decreased, and its variance was decreased. During warming stimulation, the blood volume was decreased, and its variance was decreased. CONCLUSIONS: We suggest that cyclic thermal therapy is useful to alleviate CIPN symptoms by blood circulation improvement. RBC scintigraphy can provide the quantitative information on blood volume under certain conditions such as stress, as well as rest, in peripheral tissue.

Effect of Ursodeoxycholic Acid on the Biodistribution and Excretion of Technetium-99m Radiopharmaceuticals in Rat: A Potential Image Quality Enhancer.

PURPOSE: This study aimed to investigate the effect of ursodeoxycholic acid (UDCA) on the biodistribution and excretion of technetium-99m (Tc-99m)-labeled radiopharmaceuticals. MATERIALS AND METHODS: Tc-99m hydroxy-methylene-diphosphonate (HDP), Tc-99m pertechnetate, and Tc-99m dimercaptosuccinic acid (DMSA) were injected via the tail vein of rats. After 30 min, the control group was administered saline, and the UDCA group was given UDCA orally. Scintigraphy images were acquired after 30 min and 1, 2, 3, and 4 h. Radioactivity and rate of change were compared. Tc-99m mercaptoacetyltriglycine (MAG3) imaging was also performed. RESULTS: In image analysis of Tc-99m HDP, radioactivity of the buttock was lower in the UDCA group at 4 h. Rates of change in the buttock were significantly different at 3 h-30 min and 4 h-30 min, and buttock radioactivity in the UDCA group had decreased more. In analysis of Tc-99m pertechnetate, radioactivity of the buttock was higher in the control group. Rates of change in the thyroid gland and buttock were different at 1 h-30 min, 3 h-30 min, and 4 h-30 min, with radioactivity in the UDCA group decreasing more. In the analysis of Tc-99m DMSA, while the radioactivity of the kidneys in the control group showed little decrease at 1 h-30 min, that in the UDCA group increased. In the analysis of Tc-99m MAG3 images, radioactivity and radioactivity/total body radioactivity (TBA) values for the kidneys were higher in the UDCA group at 2 min. At 5 and 10 min, radioactivity/TBA values for soft tissue in the UDCA group were lower than those in the control group. CONCLUSION: This study demonstrated that administration of UDCA increases renal excretion and soft tissue clearance of radiopharmaceuticals. This investigation could contribute to the broadening of applications of UDCA.

Voice Outcome of Total Thyroidectomy in Comparison With Administration of Recombinant Human TSH.

BACKGROUND AND OBJECTIVES: The larynx is an end-organ target for hormones, and thyroid hormone may act on the larynx. We objectively compared and analyzed the phonetic characteristics of patients who underwent total thyroidectomy before and after radioiodine therapy (RIT) according to administration of recombinant human TSH (rh-TSH). SUBJECTS AND METHODS: Ninety-one patients who had undergone a total thyroidectomy participated (50 patients without rh-TSH, 41 patients with rh-TSH). Voice samples were obtained postoperatively (Post-OP), before high-dose RIT (Pre-RIT), and after high-dose RIT (Post-RIT). Frequency-, perturbation-, and noise-related parameters were evaluated for acoustic analysis, and the voice handicap index (VHI) was used for the subjective evaluation. RESULTS: Frequency-related parameters decreased significantly in patients without rh-TSH administration, but not changed at three periods in patients with rh-TSH administration. Pitch perturbation parameters were not changed at each period in two groups, but amplitude perturbation parameters were changed significantly in two groups. The functional scores of the VHI increased significantly at Pre-RIT in two groups and physical scores increased in patients without rh-TSH at Pre-RIT. CONCLUSION: The hypothyroidism after total thyroidectomy affects phonation significantly. Our results suggest that rh-TSH administration during RIT resulted in improving voice results during RIT in the patients with total thyroidectomy.

Rodent Leukocyte Isolation and Radiolabeling for Inflammation Imaging Study.

PURPOSE: The objective of this study was to describe to develop methods of rodent leukocyte isolation and radiolabeling for in vivo inflammation imaging. METHODS: Thigh muscle inflammation was induced by injection of collagenase. Blood was collected from the jugular vein and separated by Histopaque. The collected cells were incubated in a 37 °C CO2 incubator for 1~2 h. After incubation, 99mTc-HMPAO and 18F-FDG were used to treat leukocytes followed by incubation for 30 min. 99mTc-HMPAO and 18F-FDG labeled autologous leukocytes were injected into the tail veins of rats. The images were then acquired at various time points. Image-based lesion to normal muscle ratio was compared. RESULTS: After Histopaque separation, the proportion of lymphocytes was higher than that of other cell types. After CO2 incubation, the collected leukocytes were viable, while room temperature exposed leukocytes without CO2 incubation were non-viable. Granulocytes, especially, were more quickly influenced by various conditions than the mononuclear cells. Labeling efficiencies of 99mTc-HMPAO and 18F-FDG were 4.00 ± 2.06 and 1.8%, respectively. 99mTc-HMPAO- and 18F-FDG-labeled leukocytes targeted well the inflamed lesion. 99mTc-HMPAO-labeled leukocytes, but not 18F-FDG-labeled leukocytes, were found in the abdomen activity. CONCLUSION: Inflamed lesions of rats were well visualized using autologous radiolabeled leukocytes. This method might provide good information for understanding inflammatory diseases.

Analysis of Cell Fraction of 99mTc-HMPAO Radiolabeled Leukocytes.

PURPOSE: 99mTc-HMPAO radiolabeled autologous leukocyte scintigraphy is routinely used clinically for infection imaging. Leukocytes are mostly separated via sedimentation. It is unknown whether leukocytes are clearly separated by sedimentation or selectively labeled. Therefore, in this study, the blood cell numbers were investigated after leukocyte radiolabeling to identify the cells strongly radiolabeled by 99mTc-HMPAO. METHODS: This study was performed with leftover blood samples of the patients who underwent 99mTc-HMPAO scintigraphy at Chonbuk National University Hospital (2018-2019). The blood of 22 patients was drawn for 99mTc-HMPAO scintigraphy. WBCs were separated via conventional sedimentation at our clinic and radiolabeled. The concentration of cell components was determined using an automatic hematology analyzer. The cells in the final sample injectate sample were separated using Histopaque and counted with a dose calibrator. RESULTS: The average numbers of RBCs, WBCs, and PLTs in the final injection sample were 79 ± 33, 23.26 ± 11.95, and 229.5 ± 206.57 x 103/µL, respectively. The PLT number was almost 10-fold the number of WBCs. The number of RBCs was nearly 3-fold higher than WBCs [RBC/WBC ratio = 4.67 ± 3.58, and PLT/WBC ratio = 10.65 ± 12.46]. Following Histopaque separation, the activity of each layer showed 99mTc-HMPAO labeling of WBC > RBC > PLT in order. The total activity/cell numbers of WBCs, RBCs and PLTs were 0.016 ± 0.010, 0.005 ± 0.005 and 0.003 ± 0.002, respectively (p > 0.05). CONCLUSION: Although the numbers of RBCs and PLTs were highly increased after sedimentation, their individual cellular activity was lower than that of WBCs. 99mTc-HMPAO was more selective to WBCs than RBCs or PLTs. In conclusion, a higher number of WBCs were radiolabeled compared with RBCs and PLTs.

Radioactivity Reduction of 2-Deoxy-2-[18F] Fluoro-D-Glucose by Milk and Ursodeoxycholic Acid in Preclinical Study.

PURPOSE: 2-Deoxy-2-[18F] fluoro-d-glucose positron emission tomography (18F-FDG-PET) is a less-invasive and widely used diagnostic tool for detection of malignant tumors. However, prolonged retention of 18F-FDG in the body increases radiation exposure. This study evaluated the effect of oral administration of milk and ursodeoxycholic acid (UDCA) in terms of reducing radiation exposure by 18F-FDG. METHODS: 18F-FDG radioactivity was measured using a digital γ counter in the whole body and in various organs of rats after oral administration of milk and milk plus UDCA (milk + UDCA). Western blotting was performed to measure the expression levels of G6Pase, HK 2, CREB, FoxO1, and PGC-1α in the brain, liver, small intestine, and large intestine to assess the mechanism underlying the reduction in radiation exposure from 18F-FDG by oral administration of milk and UDCA. RESULTS: We found a significant reduction in 18F-FDG radioactivity in the whole body and in the brain, liver, and small and large intestines. Expression of G6Pase was significantly increased in the above-mentioned organs in the milk and milk + UDCA groups. Expression of HK 2 was significantly decreased in the brain and small intestine in the milk and milk + UDCA groups. CREB, FoxO1, and PGC-1α expression levels in the brain, liver, and small intestine were increased in the milk and milk + UDCA groups. However, expression of PGC-1α in the large intestine in the milk and milk + UDCA groups was significantly decreased compared with that in the control group. CONCLUSION: The present study demonstrated that administration of milk and UDCA increased G6Pase expression levels and 18F-FDG release from the tissue. These results suggest milk and UDCA could be used to reduce radiation exposure from 18F-FDG after image acquisition. The mechanisms underpinning this phenomenon should be explored in a human study.

Common features of F-18 FDG PET/CT findings in Scrub Typhus: prospective study before and after antibiotics therapy.

Scrub typhus is an acute febrile illness caused by obligate intracellular organism Orientia tsutsugamushi. While there have been many reports on the evaluation of disease activity and infectious diseases using F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT), the clinical value of FDG PET/CT in scrub typhus has not been fully investigated. We enrolled 17 patients who were 18 years of age or older and clinically suspected of having scrub typhus with eschar. Clinical assessments, blood samples, and FDG PET/CT images were obtained at enrolment and again after 3 weeks. The median age of the patients was 65 years; 9 (52.9%) patients were male. On initial FDG PET/CT, the eschars showed markedly increased FDG uptake on PET imaging that improved after treatment. Generalized lymphadenopathy and splenomegaly with high FDG uptake were observed in all patients. On follow-up FDG PET/CT after appropriate therapy, FDG uptake and sizes of eschar, lymph nodes, and spleen were markedly decreased. As far as we are aware, this is the first investigation with multiple patients of FDG PET/CT in scrub typhus and the demonstration of clinical utility. FDG PET/CT imaging of scrub typhus could provide useful information about the clinical features before and after antibiotic treatment.

Incidence and severity of femoral head avascularity after femoral neck or intertrochanteric fractures on preoperative bone single photon emission computed tomography/computed tomography: preliminary study.

OBJECTIVE: The aim of the present study was to evaluate the incidence and degree of femoral head avascularity depending on the types of femoral neck or intertrochanteric fractures using preoperative bone single photon emission computed tomography (SPECT)/computed tomography (CT). PATIENTS AND METHODS: A total of 131 patients with femoral neck or intertrochanteric fractures who underwent preoperative bone SPECT/CT were enrolled. Femoral head avascularity was evaluated using bone SPECT/CT images. Visual scores ranged from 1 to 5 based on visually assessed diagnostic confidence: 1=definitely avascular femoral head, 2=likely avascular, 3=equivocal, 4=likely not avascular, and 5=definitely not avascular. In quantitative analysis, contralateral, ipsilateral, and size ratios were measured. RESULTS: Among 131 patients, 39 of 54 (72.22%) with femoral neck fractures and 23 of 77 (29.87%) with intertrochanteric fractures showed avascular femoral heads. The incidence of femoral head avascularity was significantly higher in patients with femoral neck fracture than those with intertrochanteric fracture. While the incidence and severity of femoral head avascularity increased with higher Garden stage in femoral neck fracture, neither was related to AO/Orthopaedic Trauma Association classification of intertrochanteric fracture. In addition, the number of bony fragments around intertrochanteric fractures was not a significant predictor of femoral head avascularity. CONCLUSION: Although avascular femoral head on bone SPECT/CT does not directly indicate avascular necrosis, assessing the incidence and severity of femoral head avascularity using qualitative and quantitative parameters could give clinically useful information related to the classification. Additional studies with larger sample sizes would be a next step to expand the clinical role of bone SPECT/CT.

Characterization of malignant ovarian mass on [18F]FDG PET/CT: using metabolic indices and degree of solidity.

BACKGROUND: The utility of [18F]FDG PET/CT for characterizing malignant ovarian mass has not been extensively studied. Here, we investigated various parameters that could be useful to differentiate malignant ovarian mass. METHODS: We enrolled 51 female patients (53.4±15.0 years), with 86 ovarian masses, who underwent pretreatment [18F]FDG PET/CT. Thirty six lesions were histopathologically confirmed with ovarian serous adenocarcinoma. Thirty one ovarian masses from gastric cancer and 19 masses from colorectal cancer were diagnosed by histopathological study or clinical follow-up. Ovarian masses were evaluated by size, solidity, and metabolic indices. The degree of solidity was scored from 1 to 5 according to the portion of solid and cyst. Metabolic activity was scored to be either positive (≥ liver) or negative (< liver). SUVmax (SUVovary) and the ratio of SUVmax of ovary to SUVmean of the liver (ovary/L ratio) were performed. Age, bilaterality and level of CA 125 were also compared. In statistical analysis, categorical variables were analyzed using Pearson's chi-square test, while continuous variables were evaluated either independent student's t-test or Mann-Whitney Test. Receiveroperating-characteristic analysis was used to obtain optimal cutoff values. RESULTS: Serous adenocarcinoma had significantly higher score in all metabolic indices over metastasis. However, there were no differences in all metabolic indices in ovarian metastasis. In contrast, solidity was different between metastatic mass from gastric and colorectal cancer. Ovarian metastasis from gastric cancer was significantly solid compared with that from colorectal cancer. In comparison of all three masses, solidity and all metabolic indices were significantly different. Patients with serous adenocarcinoma were older and had higher CA-125 level. Between metastases from gastric and colorectal cancer, there were no differences in age, bilaterality and CA-125. CONCLUSIONS: Metabolic indices such as SUVovary and ovary/L ratio could be useful to differentiate serous adenocarcinoma from metastasis. Furthermore, the degree of solidity could play a role in predicting the origin of metastasis.

Novel potential pyrazolopyrimidine based translocator protein ligands for the evaluation of neuroinflammation with PET.

Translocator protein (TSPO) is an interesting biological target because TSPO overexpression is associated with microglial activation caused by neuronal damage or neuroinflammation, and these activated microglia are involved in several central nervous system diseases. Herein, novel fluorinated ligands (14a-c and 16a-c) based on a 2-phenylpyrazolo[1,5-a]pyrimidin-3-yl acetamide scaffold were synthesized, and in vitro characterization of each of the novel ligands was performed to elucidate structure activity relationships. All of the newly synthesized ligands displayed nano-molar affinity for TSPO. Particularly, an in vitro affinity study suggests that 2-(5,7-diethyl-2-(4-(3-fluoro-2-methylpropoxy)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-N,N-diethylacetamide (14a), which exhibited high nano-molar affinity for TSPO and proper lipophilicity, was suitable for in vivo brain studies. Thus, radiosynthesis from tosylate precursor 13a using fluorine-18 was performed, and [18F]14a was obtained in a 31% radiochemical yield (decay-corrected). Dynamic positron emission tomography (PET) imaging studies were performed in a lipopolysaccharide (LPS)-induced neuroinflammation rat model using [18F]14a to identify the location of inflammation in the brain with a high target-to-background signal ratio. In addition, we validated that the locations of inflammatory lesions found by PET imaging were consistent with the locations observed by histological examination of dissected brains using antibodies. These results suggest that [18F]14a is a novel promising PET imaging agent for diagnosing neuroinflammation, and it may also prove to be applicable for diagnosing other diseases, including cancers associated with altered TSPO expression, using PET techniques.

Light-Triggered Radiochemical Synthesis: A Novel 18F-Labelling Strategy Using Photoinducible Click Reaction to Prepare PET Imaging Probes.

Novel probe development for positron emission tomography (PET) is leading to expanding the scope of molecular imaging. To begin responding to challenges, several biomaterials such as natural products and small molecules, peptides, engineered proteins including affibodies, and antibodies have been used in the development of targeted molecular imaging probes. To prepare radiotracers, a few bioactive materials are unique challenges to radiolabelling because of their complex structure, poor stability, poor solubility in aqueous or chemical organic solutions, and sensitivity to temperature and nonphysiological pH. To overcome these challenges, we developed a new radiolabelling strategy based on photoactivated 1,3-dipolar cycloaddition between alkene dipolarophile and tetrazole moiety containing compounds. Herein, we describe a light-triggered radiochemical synthesis via photoactivated click reaction to prepare 18F-radiolabelled PET tracers using small molecular and RGD peptide.

Synthesis and Evaluation of 2-[18F]Fluoroethyltriazolesuberohydroxamine Acid for Histone Deacetylase in a Tumor Model as a Positron Emission Tomography Radiotracer.

Histone deacetylases (HDACs) are an important regulator of expression and activity of numerous proteins in terms of epigenetic aberrations. This makes HDACs attractive for antitumor therapy and imaging in certain cancers. The authors report the radiochemical synthesis of 2-[18F]fluoroethyltriazolesuberohydroxamine acid ([18F]FETSAHA) as a HDAC-targeted radiolabel probe for positron imaging tomography/computed tomography. The authors also evaluated the in vivo tumor targeting in subcutaneously implanted RR1022 rats. [18F]FETSAHA was produced in less than 2 h with 31.2% ± 4.6% (n = 6) decay-corrected yields and specific activity of 21.4 ± 9.1 GBq/µmol (n = 6) at end of synthesis. [18F]FETSAHA showed significant radioactivity accumulation in tumors with rapid blood clearance and both gastrointestinal track and renal excretion. Tumor-to-blood and tumor-to-muscle uptake ratios in the RR1022 tumor bearing rat model were 1.21 and 1.83 and 2.75 and 2.76 at 30 and 60 min, respectively. An inhibition study of [18F]FETSAHA in the presence of excess amount of suberanilohydroximic acid (SAHA) revealed receptor specific activity accumulation. [18F]FETSAHA has favorable in vivo tumor imaging properties and may be useful for noninvasive evaluation of the correlation between cancer and HDACs.

Chitosan-Based Hydrogel Microparticles for Treatment of Carcinoma in a Rabbit VX2 Liver Tumor Model.

PURPOSE: To investigate potential of chitosan hydrogel microparticles (CHI) for treatment of VX2 carcinoma. MATERIALS AND METHODS: Two weeks after liver VX2 implantation, contrast-enhanced computerized tomographic scanning was conducted. Rabbits (n = 2) with successful tumor growth were treated with different sizes of 99mTc-labeled CHI (60-80 µm and 100-120 µm) via intra-arterial hepatic catheterization. Liver distribution of 99mTc-labeled CHI was determined by means of autoradiography, a radiation-based photographic technique. In the next part of this study, therapeutic effectiveness was examined with the use of CHI with the size range of 60-80 µm (n = 11). Tumor growth response and levels of blood liver enzymes were studied at baseline and 1 and 2 weeks after CHI treatment. RESULTS: Successful tumor growth was confirmed in all rabbits (24/24). Intrahepatic CHI with the size range of 60-80 µm resulted in liver localization in more close proximity to tumor nodule versus 100-120 µm. Baseline tumor volume was 1,909 ± 575 mm3 in animals receiving CHI versus 1,831 ± 249 mm3 in control animals (P = .342). In control animals, tumor volume markedly increased by 1,544 ± 512% at 2 weeks after sham operation versus baseline. In animals receiving CHI, tumor volume remained relatively unchanged (54 ± 6% increase; P = .007 vs control). Levels of blood aspartate transaminase (AST) and alanine transaminase (ALT) in animals receiving CHI increased 1 week after treatment (P = .032 vs control for AST; P = .000 vs control for ALT), but returned to control levels at 2 weeks. CONCLUSIONS: CHI embolization suppressed tumor growth without appreciable damages in liver function.

αv ß3 mediated tumor imaging using 99m Tc labeled NAD/monosaccharide coated ferrihydrite nanoparticles.

This study describes the synthesis of highly water-soluble, non-toxic, and biocompatible nicotinamide adenine dinucleotide (NAD)/glucosamine (=Nga1Fh) and NAD/glucosamine/gluconic acid coated ferrihydrite nanoparticles (=Nga2Fh) and their possible uses to target tumors in living animals via 99m Tc and 125 I radioisotope labeling. The structural properties were investigated using DLS, zeta potential, TEM, FT-IR, XRD, and Raman spectroscopy. The cell toxicity in CT26 cancer cells and in vivo tumor targetability in U87MG and CT26 tumor-bearing mice was further evaluated using cRGDyK-tagged and cRGDfK-tagged ferrihydrite nanoparticles. The average diameters of the resulting Nga1Fh and Nga2Fh nanoparticles were <5 to 7 and <3 nm, respectively. The Nga2Fh nanoparticles did not show cell toxicity until 0.1 mg/mL. Using gamma camera imaging, 99m Tc-cRGDfK-Nga2Fh showed the highest tumor uptake in a U87MG tumor-bearing mouse when compared with that of 99m Tc-cRGDyK-Nga2Fh and 99m Tc-Nga2Fh. The image-based tumor-to-muscle ratio by time for 99m Tc-cRGDfK-Nga2Fh was 3.8 ± 1.7, 4.2 ± 2.0, 7 ± 1.5, 13 ± 2.0, 8 ± 3.7, and 2 ± 1.6 at 5 and 30 minutes, 1, 2, 4, and 24 hours, respectively. Although further studies are needed, the NAD/monosaccharide coated ferrihydrite nanoparticles could be presented as an interesting material for a drug delivery system.