A Novel Dual-labeled Peptide for Multimodal Imaging of EGFR with L858R Mutation.

BACKGROUND: The development of molecular imaging agents targeting epidermal growth factor receptor (EGFR) with L858R mutation may help with the selection of non-small cell lung carcinoma (NSCLCL) patients who may benefit from EFGR tyrosine kinase inhibitor (TKI) therapy. OBJECTIVE: In this study, we developed 99mTc STHHYYP-GHEG-ECGK-tetramethylrhodamine (STHHYYP-ECGK-TAMRA) to target EGFR with L858R mutation in NSCLC tumors and verified its probability as a molecular imaging agent. METHODS: Fmoc solid-phase peptide synthesis was used to synthesize STHHYYP-ECGKTAMRA. 99mTc labelled STHHYYP-ECGK-TAMRA was prepared. Gamma imaging, fluorescent imaging and biodistribution were performed in murine models bearing NCI-H1975 and NCI-H1650 tumors. RESULTS: The binding affinity value (Kd) of 99mTc STHHYYP-ECGK-TAMRA was estimated to be 130.6 ± 29.2 nM in NCI-H1975 cells. The gamma camera images showed a substantial uptake of 99mTc STHHYYP-ECGK-TAMRA in the NCI-H1975 tumor. The % injected dose/gram of the NCI-H1975 tumor tissue was 2.77 ± 0.70 and 3.48 ± 1.01 at 1 and 3 h, respectively. CONCLUSION: Specific binding of 99mTc STHHYYP-ECGK-TAMRA to L858R-mutated EGFRpositive NCI-H1975 cells and tumors was demonstrated in in vivo and in vitro studies. The results suggest that 99mTc STHHYYP-ECGK-TAMRA is a good candidate agent for dualmodality imaging targeting EGFR with L858R mutation.

The utility of F-18 FDG PET/CT for diagnosis and response evaluation of hepatosplenic tuberculosis.

A 77-year-old woman underwent F-18 FDG PET/CT for evaluation of fever focus. Diffuse and intense hepatosplenic uptake was noted and lymphoma or tuberculosis was proposed. Liver biopsy revealed chronic granulomatous inflammation with Langerhans-type giant cells and necrosis. A follow-up PET/CT after anti-tuberculosis treatment revealed that the hepatosplenic uptake had resolved.

A novel dual-labeled small peptide as a multimodal imaging agent for targeting wild-type EGFR in tumors.

The epidermal growth factor receptor (EGFR) is over-expressed in various human cancer. The over-expression of EGFR in tumors is an excellent target for the development of cancer imaging agents. In the present study, we developed Tc-99m SYPIPDT-GHEG-ECG-K-tetramethylrhodamine (SYPIPDT-ECG-TAMRA) as a molecular imaging agent targeting wild-type EFGR (wtEGFR)-positive tumor cells, and verified its feasibility as molecular imaging agent. SYPIPDT-ECG-TAMRA was synthesized using Fmoc solid-phase peptide synthesis. The radiolabeling of SYPIPDT-ECG-TAMRA with Tc-99m was accomplished using ligand exchange via tartrate. Cellular uptake and binding affinity studies were performed. In vivo gamma camera imaging, ex vivo imaging and biodistribution studies were performed using NCI-H460 and SW620 tumor-bearing murine models. After radiolabeling procedures with Tc-99m, Tc-99m SYPIPDT-ECG-TAMRA complexes were prepared at high yield (> 95%). The binding affinity value (Kd) of Tc-99m SYPIPDT-ECG-TAMRA for NCI-H460 cells was estimated to be 76.5 ± 15.8 nM. In gamma camera imaging, the tumor to normal muscle uptake ratios of Tc-99m SYPIPDT-ECG-TAMRA increased with time (2.7 ± 0.6, 4.0 ± 0.9, and 6.2 ± 1.0 at 1, 2, and 3 h, respectively). The percentage injected dose per gram of wet tissue for the NCI-H460 tumor was 1.91 ± 0.11 and 1.70 ± 0.22 at 1 and 3 h, respectively. We developed Tc-99m SYPIPDT-ECG-TAMRA, which is dual-labeled with both radioisotope and fluorescence. In vivo and in vitro studies demonstrated specific uptake of Tc-99m SYPIPDT-ECG-TAMRA into wtEGFR-positive NCI-H460 cells and tumors. Thus, the results of the present study suggest that Tc-99m SYPIPDT-ECG-TAMRA is a potential dual-modality imaging agent targeting wtEGFR.

Clinical impact of radioactive iodine dose selection based on the number of metastatic lymph nodes in patients with papillary thyroid carcinoma: A multicenter retrospective cohort study.

OBJECTIVE: The aim of this study is to investigate whether the number of metastatic lymph nodes (LNs) could be used as a basis in the radioactive iodine (RAI) dose selection for patients with papillary thyroid carcinoma (PTC). PATIENTS: A total of 595 patients with PTC who received first RAI therapy after total or near-total thyroidectomy and had no evidence of disease in treatment response assessment were retrospectively enroled from five hospitals. The patients were classified into two subgroups based on the number of metastatic LNs (>5). The multivariate Cox-proportional hazard model was performed to identify the significant factors for recurrence prediction in each group as well as all enroled patients. RESULTS: Overall, 22 (3.7%) out of 595 patients had the recurrent disease during the follow-up period. The number of metastatic LNs (>5) was only a significant factor for recurrence prediction in all enroled patients (odds ratio: 7.834, p < .001). In the subgroup with ≤5 metastatic LNs, the presence of extrathyroidal extension was only associated with recurrence (odds ratio: 7.333, p = .024) in multivariate analysis. RAI dose was significantly associated with recurrence rate in which the patients with high-dose RAI (3.7 GBq or higher) had less incidence of recurrence than those with low-dose RAI (1.11 GBq) in the subgroup with more than five metastatic LNs (odds ratio: 6.533, p = .026). CONCLUSIONS: High-dose RAI (≥3.7 GBq) therapy significantly lowered the recurrence rate in patients with more than five metastatic LNs. Therefore, RAI dose should be determined based on the number of metastatic LNs as well as conventional risk factors.

Dual-labeled prostate-specific membrane antigen (PSMA)-targeting agent for preoperative molecular imaging and fluorescence-guided surgery for prostate cancer.

The objective of this study was to report the synthesis and characteristics of a dual modality imaging agent, Tc-99m GRFLTGGTGRLLRIS-GHEG-ECG-K(-5-carboxy-X-rhodamine)-NH2 (GRFLT-ECG-ROX), and to verify its feasibility as both molecular imaging and intraoperative guidance agent. GRFLT-ECG-ROX was synthesized using Fmoc solid-phase peptide synthesis. Radiolabeling of GRFLT-ECG-ROX with Tc-99m was accomplished using ligand exchange via tartrate. Binding affinity and in vitro cellular uptake studies were performed. Gamma camera imaging, biodistribution, and ex vivo imaging studies were performed using LNCaP and PC-3 tumor-bearing murine models. Surgical removal of tumor nodules in murine models with peritoneal carcinomatosis was performed under a fluorescence imaging system. After radiolabeling procedures with Tc-99m, Tc-99m GRFLT-ECG-ROX complexes were prepared in high yield (>96%). The binding affinity value (Kd ) of Tc-99m GRFLT-ECG-ROX for LNCaP cells was estimated to be 9.5 ± 1.3 nM. In gamma camera imaging, the tumor to normal muscle uptake ratios of Tc-99m GRFLT-ECG-ROX increased with time (3.1 ± 0.2, 4.0 ± 0.4, and 6.3 ± 0.9 at 1, 2, and 3 h, respectively). Under real-time optical imaging, the removal of visible nodules was successfully performed. Thus, Tc-99m GRFLT-ECG-ROX could provide both preoperative molecular imaging and fluorescence imaging guidance for tumor removal.

Incidental Detection of Iliac Artery Occlusion on 3-Phase Bone Scintigraphy.

Our patient was a 72-year-old man with absent activity of the right femoral artery and mildly decreased Tc-DPD activity on the right leg as indicated on the blood pool and delayed images, respectively. Subsequent peripheral angiography revealed a total occlusion of the right external iliac artery with good collateral flow. Careful review of blood flow and blood pool images of 3-phase bone scintigraphy could provide additional information about peripheral vascular disease.

A novel dual-modality imaging agent targeting folate receptor of tumor for molecular imaging and fluorescence-guided surgery.

OBJECTIVE: Folate receptor (FR) is an ideal target for cancer imaging because it is frequently overexpressed in major types of human tumor, whereas its expression in normal organs is highly limited. Combining nuclear and fluorescence-imaging techniques provides a novel approach for cancer imaging and monitoring the surgery. The objective of this study was to report the synthesis and characteristics of a dual-modality imaging agent, Tc-99m Folate-Gly-His-Glu-Gly-Glu-Cys-Gly-Lys(-5-carboxy-X-rhodamine)-NH2 (Folate-ECG-ROX), and verify its feasibility as both molecular imaging agent and intra-operative guidance. METHODS: Folate-ECG-ROX was synthesized using Fmoc solid-phase peptide synthesis. Radiolabeling of Folate-ECG-ROX with Tc-99m was done using ligand exchange via tartrate. Binding affinity and in vitro cellular uptake studies were performed. Gamma camera imaging, biodistribution and ex vivo imaging studies were performed using KB and HT-1080 tumor-bearing murine models. Tumor tissue slides were prepared and analyzed with immunohistochemistry staining and confocal microscopy. Surgical removal of tumor nodules in murine models with peritoneal carcinomatosis was performed under the fluorescence-imaging system. RESULTS: After radiolabeling procedures with Tc-99m, Tc-99m Folate-ECG-ROX complexes were prepared in high yield (> 97%). The binding affinity value (Kd) of Tc-99m Folate-ECG-ROX for KB cells was estimated to be 6.9 ± 0.9 nM. In gamma camera imaging, tumor to normal muscle uptake ratio of Tc-99m Folate-ECG-ROX increased with time (3.4 ± 0.4, 4.4 ± 0.7, and 6.6 ± 0.8 at 1, 2, and 3 h, respectively). In biodistribution study, %IA/g for KB tumor was 2.50 ± 0.80 and 4.08 ± 1.16 at 1 and 3 h, respectively. Confocal microscopy with immunohistochemistry staining detected strong Tc-99m Folate-ECG-ROX fluorescence within KB tumor tissue which is correlating with the fluorescent activity of anti-FR antibody. Under real-time optical imaging, the removal of visible nodules was successfully performed. CONCLUSIONS: In vivo and in vitro studies revealed substantial and specific uptake of Tc-99m Folate-ECG-ROX in FR-positive tumors. Thus, Tc-99m Folate-ECG-ROX could provide both pre-operative molecular imaging and fluorescence image-guidance for tumor.

Tc-99m and Fluorescence-Labeled Anti-Flt1 Peptide as a Multimodal Tumor Imaging Agent Targeting Vascular Endothelial Growth Factor-Receptor 1.

PURPOSE: We developed a Tc-99m and fluorescence-labeled peptide, Tc-99m TAMRA-GHEG-ECG-GNQWFI, to target tumor cells, and evaluated the diagnostic performance as a dual-modality imaging agent for tumor in a murine model. METHODS: TAMRA-GHEG-ECG-GNQWFI was synthesized using Fmoc solid-phase peptide synthesis. Radiolabeling of TAMRA-GHEG-ECG-GNQWFI with Tc-99m was done using ligand exchange via tartrate. Binding affinity and in vitro cellular uptake studies were performed. Gamma camera imaging, biodistribution, and ex vivo imaging studies were performed in murine models with U87MG tumors. Tumor tissue slides were prepared and analyzed with immunohistochemistry using confocal microscopy. RESULTS: After radiolabeling procedures with Tc-99m, Tc-99m TAMRA-GHEG-ECG-GNQWFI complexes were prepared in high yield (> 95%). The K d of Tc-99m TAMRA-GHEG-ECG-GNQWFI determined by saturation binding was 29.5 ± 4.5 nM. Confocal microscopy images of U87MG cells incubated with TAMRA-GHEG-ECG-GNQWFI showed strong fluorescence in the cytoplasm. Gamma camera imaging revealed substantial uptake of Tc-99m TAMRA-GHEG-ECG-GNQWFI in tumors. Tumor uptake was effectively blocked by the co-injection of an excess concentration of GNQWFI. Specific uptake of Tc-99m TAMRA-GHEG-ECG-GNQWFI was assessed by biodistribution, ex vivo imaging, and immunohistochemistry stain studies. CONCLUSIONS: In vivo and in vitro studies revealed substantial and specific uptake of Tc-99m TAMRA-GHEG-ECG-GNQWFI in tumor cells. Tc-99m TAMRA-GHEG-ECG-GNQWFI could be a good candidate dual-modality imaging agent for tumors.

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.

A novel Tc-99m and fluorescence-labeled arginine-arginine-leucine-containing peptide as a multimodal tumor imaging agent in a murine tumor model.

We developed a Tc-99m and TAMRA-labeled peptide, Tc-99m arginine-arginine-leucine (RRL) peptide (TAMRA-GHEG-ECG-RRL), to target tumor cells and evaluated the diagnostic performance of Tc-99m TAMRA-GHEG-ECG-RRL as a dual-modality imaging agent for tumor in a murine model. TAMRA-GHEG-ECG-RRL was synthesized using Fmoc solid-phase peptide synthesis. Binding affinity and in vitro cellular uptake studies were performed. Gamma camera imaging, biodistribution, and ex vivo imaging studies were performed in murine models with PC-3 tumors. Tumor tissue slides were prepared and analyzed with immunohistochemistry using confocal microscopy. After radiolabeling procedures with Tc-99m, Tc-99m TAMRA-GHEG-ECG-RRL complexes were prepared in high yield (>96%). The Kd of Tc-99m TAMRA-GHEG-ECG-RRL determined by saturation binding was 41.7 ± 7.8 nM. Confocal microscopy images of PC-3 cells incubated with TAMRA-GHEG-ECG-RRL showed strong fluorescence in the cytoplasm. Gamma camera imaging revealed substantial uptake of Tc-99m TAMRA-GHEG-ECG-RRL in tumors. Tumor uptake was effectively blocked by the coinjection of an excess concentration of RRL. Specific uptake of Tc-99m TAMRA-GHEG-ECG-RRL was confirmed by biodistribution, ex vivo imaging, and immunohistochemistry stain studies. In conclusion, in vivo and in vitro studies revealed substantial uptake of Tc-99m TAMRA-GHEG-ECG-RRL in tumors. Tc-99m TAMRA-GHEG-ECG-RRL has potential as a dual-modality tumor imaging agent.

Transiently Altered Distribution of F-18 FDG in a Patient with Subacute Thyroiditis.

F-18 fluorodeoxyglucose (FDG) is a highly influential radiotracer that provides valuable information in many cancer types. However, the normal biodistribution of F-18 FDG is often variable and can be altered by intrinsic or iatrogenic factors. We report a case of diffuse symmetrically increased skeletal muscle uptake and relatively decreased hepatic uptake on F-18 FDG PET/CT in a 57-year-old female with pulmonary adenocarcinoma. Detailed clinical evaluation and retrospective radiologic evaluation revealed that she had been diagnosed with subacute thyroiditis 2 weeks ago. After 6 weeks, F-18 FDG distribution was normalized at the follow-up PET/CT study.

Usefulness of Tc-99m Pertechnetate SPECT/CT in the Diagnosis of Testicular Infarction After Inguinal Herniorrhaphy.

A 77-year-old male underwent open repair for a right indirect inguinal hernia and complained of right scrotal pain on the third postoperative day. Color Doppler imaging revealed decreased blood flow with heterogeneous hypoechogenicity in the right testis. A Tc-99m pertechnetate testicular scan showed diffuse hyperemia and increased uptake in the right scrotum. Additional SPECT/CT revealed a photon defect in the right testicle with increased uptake in the peri-testicular area. A subsequent operation revealed a large hematoma in the right spermatic cord and consequent right testicular infarction, and right orchiectomy was performed.

Synthesis and evaluation of Tc-99m and fluorescence-labeled elastin-derived peptide, VAPG for multimodal tumor imaging in murine tumor model.

We developed a Tc-99m and fluorescence-labeled peptide, Tc-99m TAMRA-GHEG-ECG-VAPG to target tumor cells and evaluated the diagnostic performance as a dual-modality imaging agent for tumor in a murine model. TAMRA-GHEG-ECG-VAPG was synthesized by using Fmoc solid-phase peptide synthesis. Radiolabeling of TAMRA-GHEG-ECG-VAPG with Tc-99m was done by using ligand exchange via tartrate. Binding affinity and in vitro cellular uptake studies were performed. Gamma camera imaging, biodistribution, and ex vivo imaging studies were performed in murine models with SW620 tumors. Tumor tissue slides were prepared and analyzed with immunohistochemistry by using confocal microscopy. After radiolabeling procedures with Tc-99m, Tc-99m TAMRA-GHEG-ECG-VAPG complexes were prepared in high yield (>96%). The Kd of Tc-99m TAMRA-GHEG-ECG-VAPG determined by saturation binding was 16.8 ± 3.6 nM. Confocal microscopy images of SW620 cells incubated with TAMRA-GHEG-ECG-VAPG showed strong fluorescence in the cytoplasm. Gamma camera imaging revealed substantial uptake of Tc-99m TAMRA-GHEG-ECG-VAPG in tumors. Tumor uptake was effectively blocked by the coinjection of an excess concentration of VAPG. Specific uptake of Tc-99m TAMRA-GHEG-ECG-VAPG was confirmed by biodistribution, ex vivo imaging, and immunohistochemistry stain studies. In vivo and in vitro studies revealed substantial uptake of Tc-99m TAMRA-GHEG-ECG-VAPG in tumor cells. Tc-99m TAMRA-GHEG-ECG-VAPG has potential as a dual-modality tumor imaging agent.

A novel Tc-99m and fluorescence labeled peptide as a multimodal imaging agent for targeting angiogenesis in a murine hindlimb ischemia model.

The serine-aspartic acid-valine (SDV) peptide binds specifically to integrin αvß3. We developed a Tc-99m and TAMRA labeled peptide, Tc-99m SDV-ECG-K-TAMRA for multimodal imaging of angiogenesis. Tc-99m SDV-ECG-K-TAMRA was prepared in high yield (>96%) and showed low cytotoxicity. Tc-99m tetrofosmin images 1 week after operation, revealed significantly decreased perfusion of the ischemic hindlimb, and the perfusion recovered gradually for 4 weeks. In contrast, Tc-99m SDV-ECG-K-TAMRA uptake was maximal 1 week after the operation (ischemic-to-non-ischemic uptake ratio =5.03±1.01) and decreased gradually. The ischemic-to-non-ischemic ratio of Tc-99m SDV-ECG-K-TAMRA and Tc-99m tetrofosmin was strongly negatively correlated (r =-0.94). A postmortem analysis revealed increased angiogenesis markers and uptake of Tc-99m SDV-ECG-K-TAMRA by ischemic tissue. Our in vivo and in vitro studies revealed substantial uptake of Tc-99m SDV-ECG-K-TAMRA by ischemic tissue. Tc-99m SDV-ECG-K-TAMRA could be a good candidate dual-modality imaging agent to assess angiogenesis.

A novel Tc-99 m and fluorescence labeled peptide as a multimodal imaging agent for targeting angiogenesis in a murine tumor model.

The serine-aspartic acid-valine (SDV) peptide binds specifically to integrin αV ß3 . In the present study, we successfully developed a TAMRA-GHEG-ECG-SDV peptide labeled with both Tc-99 m and TAMRA to target the integrin αV ß3 of tumor cells; furthermore, we evaluated the diagnostic performance of Tc-99 m TAMRA-GHEG-ECG-SDV as a dual-modality imaging agent for tumor of the murine model. TAMRA-GHEG-ECG-SDV was synthesized using Fmoc solid-phase peptide synthesis. Radiolabeling of TAMRA-GHEG-ECG-SDV with Tc-99 m was done using ligand exchange methods. Labeling stability and cytotoxicity studies were performed. Gamma camera imaging, biodistribution and ex vivo imaging studies were performed in murine models with HT-1080 and HT-29 tumors. A tumor tissue slide was prepared and analyzed using confocal microscopy. After radiolabeling procedures with Tc-99 m, the Tc-99 m TAMRA-GHEG-ECG-SDV complexes were prepared in high yield (>99%). In the gamma camera imaging study, a substantial uptake of Tc-99 m TAMRA-GHEG-ECG-SDV into HT-1080 tumor (integrin αV ß3 positive) and low uptake of Tc-99 m TAMRA-GHEG-ECG-SDV into HT-29 tumor (integrin αV ß3 negative) were demonstrated. A competition study revealed that HT-1080 tumor uptake was effectively blocked by the co-injection of an excess concentration of SDV. Specific uptake of Tc-99 m TAMRA-GHEG-ECG-SDV was confirmed by biodistribution, ex vivo imaging and confocal microscopy studies. Our in vivo and in vitro studies revealed substantial uptake of Tc-99 m TAMRA-GHEG-ECG-SDV in the integrin αV ß3 -positive tumor. Tc-99 m TAMRA-GHEG-ECG-SDV could be a good candidate for a dual-modality imaging agent targeting tumor angiogenesis. Copyright © 2016 John Wiley & Sons, Ltd.

Tc­99m Ser­Asp­Val­Glu­Cys­Gly: A novel Tc­99m labeled hexapeptide for molecular and non­invasive tumor imaging.

In a ProteoChip­based screening system and subsequent studies, serine­aspartic acid­valine (SDV) was demonstrated to specifically bind to integrin αvß3. An SDV­containing peptide could target the tumor vessel and it may be an effective replacement for molecular imaging of the tumor. In the present study, a hexapeptide, SDV­glutamic acid­cysteine­glycine (ECG), was developed and evaluated its diagnostic performance as a tumor imaging agent in tumor­bearing mice. The hexapeptide SDV­ECG was synthesized using Fmoc solid­phase peptide synthesis. Following radiolabeling procedures with technetium­99m, the Tc­99m SDV­ECG complexes were prepared at high yields (>97%). The uptake of Tc­99m SDV­ECG within HT­1080 tumor cells (integrin αvß3­positive) was confirmed by in vitro studies. γ­camera imaging revealed substantial uptake of Tc­99m SDV­ECG in the HT­1080 cell line tumor murine model. With the co­injection of excess SDV, tumoral uptake was blocked. Furthermore, HT­29 tumor cells (integrin αvß3­negative) and inflammatory lesions demonstrated minimal uptake of Tc­99m SDV­ECG. In the present study, Tc­99m SDV­ECG was developed as a novel Tc­99m agent for tumor imaging. The current in vitro and in vivo studies demonstrated specific functions of Tc­99m SDV­ECG in tumor imaging.

Preclinical evaluation of isostructural Tc-99m- and Re-188-folate-Gly-Gly-Cys-Glu for folate receptor-positive tumor targeting.

OBJECTIVE: The purpose of the present study was to prepare isostructural Tc-99m- and Re-188-folate-Gly-Gly-Cys-Glu (folate-GGCE), and to evaluate the feasibility of their use for folate receptor (FR)-targeted molecular imaging and as theranostic agents in a mouse tumor model. METHODS: Folate-GGCE was synthesized using solid-phase peptide synthesis and radiolabeled with Tc-99m or Re-188. Radiochemical characterization was performed by radio-high-performance liquid chromatography. The biodistribution of Tc-99m-folate-GGCE was studied, with or without co-injection of excess free folate, in mice bearing both FR-positive (KB cell) and FR-negative (HT1080 cell) tumors. Biodistribution of Re-188-folate-GGCE was studied in mice bearing KB tumors. Serial planar scintigraphy was performed in the dual tumor mouse model after intravenous injection of Tc-99m-folate-GGCE. Serial micro-single photon emission computed tomography/computed tomography (SPECT/CT) studies were performed, with or without co-injection of excess free folate, in the mouse tumor model after injection of Tc-99m-folate-GGCE or Re-188-folate-GGCE. RESULTS: The radiolabeling efficiency and radiochemical stability of Tc-99m- and Re-188-folate-GGCE were more than 95 % for up to 4 h after radiolabeling. Uptake of Tc-99m-folate-GGCE at 1, 2, and 4 h after injection in KB tumor was 16.4, 23.2, and 17.6 % injected dose per gram (%ID/g), respectively. This uptake was suppressed by 97.4 % when excess free folate was co-administered. Tumor:normal organ ratios at 4 h for blood, liver, lung, muscle, and kidney were 54.3, 25.2, 38.3, 97.8, and 0.3, respectively. Tumor uptake of Re-188-folate-GGCE at 2, 4, 8, and 16 h after injection was 17.4, 21.7, 24.1, and 15.6 %ID/g, respectively. Tumor:normal organ ratios at 8 h for blood, liver, lung, muscle, and kidney were 126.8, 21.9, 54.8, 80.3, and 0.4, respectively. KB tumors were clearly visualized at a high intensity using serial scintigraphy and micro-SPECT/CT in mice injected with Tc-99m- or Re-188-folate-GGCE. The tumor uptake of these molecules was completely suppressed when excess free folate was co-administered. CONCLUSION: Isostructural Tc-99m- and Re-188-folate-GGCE showed high and FR-specific uptake by tumors and generally favorable tumor:normal organ ratios. The tumor targeting capabilities of Tc-99m- and Re-188-folate-GGCE were clearly evident on serial imaging studies. This isostructural pair may have potential diagnostic and theranostic applications for FR-positive tumors.

Tc-99m Glu-Cys-Gly-His-Gly-Lys (ECG-HGK), a novel Tc-99m labeled hexapeptide for molecular tumor imaging.

Domain 5 of kinin-free high molecular weight kininogen inhibits the adhesion of many tumor cell lines, and it has been reported that the histidine-glycine-lysine (HGK)-rich region might be responsible for inhibition of cell adhesion. The authors developed HGK-containing hexapeptide, glutamic acid-cysteine-glycine (ECG)-HGK, and evaluated the utility of Tc-99m ECG-HGK for tumor imaging. Hexapeptide, ECG-HGK was synthesized using Fmoc solid-phase peptide synthesis. Radiolabeling efficiency was evaluated. The uptake of Tc-99m ECG-HGK within HT-1080 cells was evaluated in vitro. In HT-1080 tumor-bearing mice, gamma imaging and biodistribution studies were performed. The complexes Tc-99m ECG-HGK was prepared in high yield. The uptake of Tc-99m ECG-HGK within the HT-1080 tumor cells had been demonstrated by in vitro studies. The gamma camera imaging in the murine model showed that Tc-99m ECG-HGK was accumulated substantially in the HT-1080 tumor (tumor-to-muscle ratio = 5.7 ± 1.4 at 4 h), and the tumoral uptake was blocked by the co-injection of excess HGK (tumor-to-muscle ratio = 2.8 ± 0.6 at 4 h). In the present study, Tc-99m ECG-HGK was developed as a new tumor imaging agents. Our in vitro and in vivo studies revealed specific function of Tc-99m ECG-HGK for tumor imaging.

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.