Myoung Hyoun Kim

Synthesis and evaluation of novel Tc-99 m labeled NGR-containing hexapeptides as tumor imaging agents

Asparagine-glycine-arginine (NGR)-containing peptides targeting aminopeptidase N (APN)/CD13 can be an excellent candidate for targeting ligands in molecular tumor imaging. In this study, we developed two NGR-containing hexapeptides, and evaluated the diagnostic performance of Tc-99m labeled hexapeptides as molecular imaging agents in an HT-1080 fibrosarcoma-bearing murine model. Peptides were synthesized using Fmoc solid-phase peptide synthesis. Radiochemical purity of Tc-99m was evaluated using instant thin-layer chromatography. The uptake of two NGR-containing hexapeptides within HT-1080 cells was evaluated in vitro. In HT-1080 fibrosarcoma tumor-bearing mice, gamma images were acquired. A biodistribution study was performed to calculate percentage of the injected dose per gram of tissue (%ID/g). Two hexapeptides, glutamic acid-cysteine-glycine (ECG)-NGR and NGR-ECG were successfully synthesized. After radiolabeling procedures with Tc-99m, the complexes Tc-99m hexapeptides were prepared in high yield. The uptake of Tc-99m ECG-NGR within the tumor cells had been assured by in vitro studies. The gamma camera imaging in the murine model showed that Tc-99m ECG-NGR was accumulated substantially in the subcutaneously engrafted tumor. However, Tc-99m NGR-ECG was accumulated minimally in the tumor. Two NGR-containing hexapeptides, ECG-NGR and NGR-ECG were developed as molecular imaging agents to target APN/CD13 in HT-1080 fibrosarcoma. Tc-99m ECG-NGR showed a significant uptake in the tumor, and it is a good candidate for tumor imaging.

Novel Tc-99m labeled ELR-containing 6-mer peptides for tumor imaging in epidermoid carcinoma xenografts model: a pilot study

ObjectiveELR-containing peptides targeting CXCR2 could be the excellent candidate for targeting ligand of molecular tumor imaging. In this study, we had developed two ELR-containing 6-mer peptides and evaluated the diagnostic performance of Tc-99m labeled 6-mer peptides as a molecular imaging agent in murine models bearing KB epidermoid carcinoma.MethodsPeptides were synthesized using Fmoc solid phase peptide synthesis. Radiolabeling efficiency with Tc-99m was evaluated using instant thin-layer chromatography. In KB epidermoid cancer-bearing mice, gamma images had acquired and tumor-to-muscle uptake ratio was calculated. Competition and biodistribution studies had performed.ResultsTwo 6-mer peptides, ELR-ECG and ECG-ELR were successfully synthesized. After radiolabeling procedures with Tc-99m, the complex Tc-99m ELR-ECG and Tc-99m ECG-ELR were prepared in high yield. In the gamma camera imaging of murine model, Tc-99m ELR-ECG was substantially accumulated in the subcutaneously engrafted tumor and tumor uptake had been suppressed by the free ELR co-injection. However, Tc-99m ECG-ELR was minimally accumulated in the tumor.ConclusionsTwo ELR-containing 6-mer peptides, ELR-ECG and ECG-ELR, were developed as a molecular imaging agent to target CXCR2 of epidermoid carcinoma. Tc-99m ELR-ECG had showed significant uptake in tumor and it was good candidate for a tumor imaging.

Synthesis and evaluation of Tc-99m-labeled RRL-containing peptide as a non-invasive tumor imaging agent in a mouse fibrosarcoma model.

ObjectiveArginine–arginine–leucine (RRL) is considered a tumor endothelial cell-specific binding sequence. RRL-containing peptide targeting tumor vessels is an excellent candidate for tumor imaging. In this study, we developed RRL-containing hexapeptides and evaluated their feasibility as a tumor imaging agent in a HT-1080 fibrosarcoma-bearing murine model.MethodsThe hexapeptide, glutamic acid–cysteine–glycine (ECG)–RRL was synthesized using Fmoc solid-phase peptide synthesis. Radiolabeling efficiency was evaluated using instant thin-layer chromatography. Uptake of Tc-99m ECG–RRL within HT-1080 cells was evaluated in vitro by confocal microscopy and cellular binding affinity was calculated. Gamma images were acquired In HT-1080 fibrosarcoma tumor-bearing mice, and the tumor-to-muscle uptake ratio was calculated. The inflammatory-to-normal muscle uptake ratio was also calculated in an inflammation mouse model. A biodistribution study was performed to calculate %ID/g.ResultsA high yield of Tc-99m ECG–RRL complexes was prepared after Tc-99m radiolabeling. Binding of Tc-99m ECG–RRL to tumor cells had was confirmed by in vitro studies. Gamma camera imaging in the murine model showed that Tc-99m ECG–RRL accumulated substantially in the subcutaneously engrafted tumor and that tumoral uptake was blocked by co-injecting excess RRL. Moreover, Tc-99m ECG–RRL accumulated minimally in inflammatory lesions.ConclusionsWe successfully developed Tc-99m ECG–RRL as a new tumor imaging candidate. Specific tumoral uptake of Tc-99m ECG–RRL was evaluated both in vitro and in vivo, and it was determined to be a good tumor imaging candidate. Additionally, Tc-99m ECG–RRL effectively distinguished between cancerous tissue and inflammatory lesions.

Os vesalianum pedis detected with bone SPECT/CT.

We present an 18-year-old man with pain at the lateral aspect of his left foot. Radiograph showed abnormal ossicle in the proximal aspect of the left fifth metatarsal tuberosity, which was articulated with the fifth metatarsal and cuboid bones. Bone scintigraphy and SPECT/CT demonstrated increased uptakes at the ossicles in the proximal aspect of both fifth metatarsal bones. CT revealed that the ossicle and the adjacent bones have well-corticated margins. The diagnosis was os vesalianum, a rare accessory bone of the foot. We have reported the SPECT/CT bone scan findings of the os vesalianum.

Extrathyroidal Radioiodine Accumulation in a Fibroadenoma of the Breast.

A 45-year-old woman with a differentiated thyroid carcinoma received adjuvant radioiodine therapy following total thyroidectomy and left modified radical neck dissection. A posttherapy planar radioiodine scan showed multifocal uptake in the thyroid bed and left chest. SPECT/CT revealed a fibroadenoma in the left breast. Six months later, an I scan showed no iodine avidity in the breast fibroadenoma, whereas ultrasonography showed no significant change in the size of the fibroadenoma. Altered radioiodine uptake of a breast fibroadenoma can be observed on follow-up scans after cytotoxic radioiodide treatment in patients with differentiated thyroid carcinoma.

Incidental Detection of Urinary Leakage on FDG PET/CT Imaging for Staging of Gastric Cancer.

A 71-year-old woman presented to the emergency department with right flank pain and dysuria. An abdominal CT scan detected a gastric malignancy and hydronephrosis with urinary leakage of the right kidney. Percutaneous nephrostomy was performed on the right kidney. F-FDG PET/CT for staging the gastric malignancy revealed additional urinary leakage of the contralateral kidney. The interest in this case is the incidental detection of unexpected urinary leakage during an oncologic assessment with FDG PET/CT.

Lymphoscintigraphy revealed chyloperitoneum after gastrectomy for gastric cancer.

A 74-year-old woman underwent the radical near-total gastrectomy with Billroth II anastomosis and lymph nodes dissection due to the advanced gastric cancer. On the seventh day after gastrectomy, edema on the both legs and abdominal distention were developed. On the lymphoscintigraphy, the abnormal activity in the peritoneal cavity was revealed, and chyloperitoneum was diagnosed, and additional dynamic scans could localize the chyle leakage focus. Localization of chyle leakage focus enabled surgeon to establish the proper operative plan for the injured lymphatics.

Synovial hemangioma of Hoffa fat pad demonstrated by RBC SPECT/CT.

Synovial hemangioma of Hoffa fat pad is an extremely rare disease, which occurs in the knee joints. Because synovial hemangioma often shows nonspecific symptoms, such as pain, swelling, limping, or limitation of motion, diagnosis could be delayed in many cases. We present a 7-year-old boy referred to our department for Tc red blood cell (RBC) scan for the confirmation of hemangioma suggested by the MRI. RBC scan demonstrated intense radioactivity accumulation in Hoffa pad of right knee joint, and subsequent excision biopsy revealed the mass as venous hemangioma.

Effect of 18F-FDG Administration on Measurements of Bone Mineral Density and Body Composition by Dual-Energy X-ray Absorptiometry

The purpose of this study was to determine whether antecedent administration of ¹⁸F-fluorodeoxyglucose (FDG) used in positron emission tomography (PET) scanning results in corruption of bone mineral density (BMD) and body composition measured by dual-energy X-ray absorptiometry (DXA) system. DXA measurements of BMD and body composition had been performed twice, before and after ¹⁸F-FDG PET scan in 30 patients. The comparison of pre-values and post-values of all BMD values showed a decrease after the injection. However, only the decrease of whole-body BMD (WB-BMD) was statistically significant (p < 0.05). Whole-body fat mass had increased and whole-body lean body mass had decreased after the injection of ¹⁸F-FDG, and these were statistically significant (p < 0.05). There is statistically significant correlation between the injected ¹⁸F-FDG dose and a decrease of WB-BMD (r = -0.405; p < 0.05). The findings of this study suggest that when both ¹⁸F-FDG PET and DXA measurements for whole-body composition are performed in close-time proximity, ¹⁸F-FDG PET scans should follow the DXA measurement. Otherwise, BMD measurements of total femur or lumbar spine could be followed by ¹⁸F-FDG PET in close-time proximity.

Incidental Detection of Peri-Renal Hemorrhage on F-18 FDG PET/CT Imaging in a Patient with Polycystic Kidney Disease

A 72-year-old male patient with a history of polycystic kidney disease and lung malignancy underwent F-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) for the evaluation of tumor recurrence. The FDG PET/CT and subsequent non-enhanced CT scans revealed a hemorrhage in the peri-renal space of the left original kidney. Interesting in this case was the incidental detection of unexpected peri-renal hemorrhage during an oncologic assessment with FDG PET/CT.