scholarly journals Synthesis of Novel, Dual-Targeting 68Ga-NODAGA-LacN-E[c(RGDfK)]2 Glycopeptide as a PET Imaging Agent for Cancer Diagnosis

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 796
Author(s):  
Barbara Gyuricza ◽  
Judit P. Szabó ◽  
Viktória Arató ◽  
Dániel Szücs ◽  
Adrienn Vágner ◽  
...  
Keyword(s):  
Cancer Diagnosis ◽  
Pet Imaging ◽  
Solid Phase ◽  
Click Reaction ◽  
Radiochemical Yield ◽  
Log P ◽  
Αvβ3 Integrin ◽  
Radiolabeled Peptides ◽  
Galectin 3

Radiolabeled peptides possessing an Arg-Gly-Asp (RGD) motif are widely used radiopharmaceuticals for PET imaging of tumor angiogenesis due to their high affinity and selectivity to αvβ3 integrin. This receptor is overexpressed in tumor and tumor endothelial cells in the case of numerous cancer cell lines, therefore, it is an excellent biomarker for cancer diagnosis. The galectin-3 protein is also highly expressed in tumor cells and N-acetyllactosamine is a well-established ligand of this receptor. We have developed a synthetic method to prepare a lactosamine-containing radiotracer, namely 68Ga-NODAGA-LacN-E[c(RGDfK)]2, for cancer diagnosis. First, a lactosamine derivative with azido-propyl aglycone was synthetized. Then, NODAGA-NHS was attached to the amino group of this lactosamine derivative. The obtained compound was conjugated to an E[c(RGDfK)]2 peptide with a strain-promoted click reaction. We have accomplished the radiolabeling of the synthetized NODAGA-LacN-E[c(RGDfK)]2 precursor with a positron-emitting 68Ga isotope (radiochemical yield of >95%). The purification of the labeled compound with solid-phase extraction resulted in a radiochemical purity of >99%. Subsequently, the octanol–water partition coefficient (log P) of the labeled complex was determined to be −2.58. In addition, the in vitro stability of 68Ga-NODAGA-LacN-E[c(RGDfK)]2 was investigated and it was found that it was stable under the examined conditions.

68Ga-labeled HBED-CC Variant of uPAR Targeting Peptide AE105 Compared with 68Ga-NODAGA-AE105

2019 ◽  
Vol 18 (9) ◽  
pp. 1289-1294 ◽  
Author(s):  
Kusum Vats ◽  
Rohit Sharma ◽  
Haladhar D. Sarma ◽  
Drishty Satpati ◽  
Ashutosh Dash
Keyword(s):  
Solid Phase ◽  
Evaluation Studies ◽  
Radiochemical Yield ◽  
In Vivo Evaluation ◽  
Peptide Conjugates ◽  
Biodistribution Studies ◽  
Target Organs ◽  
U87mg Tumor

Aims: The urokinase Plasminogen Activator Receptors (uPAR) over-expressed on tumor cells and their invasive microenvironment are clinically significant molecular targets for cancer research. uPARexpressing cancerous lesions can be suitably identified and their progression can be monitored with radiolabeled uPAR targeted imaging probes. Hence this study aimed at preparing and evaluating two 68Ga-labeled AE105 peptide conjugates, 68Ga-NODAGA-AE105 and 68Ga-HBED-CC-AE105 as uPAR PET-probes. Method: The peptide conjugates, HBED-CC-AE105-NH2 and NODAGA-AE105-NH2 were manually synthesized by standard Fmoc solid phase strategy and subsequently radiolabeled with 68Ga eluted from a commercial 68Ge/68Ga generator. In vitro cell studies for the two radiotracers were performed with uPAR positive U87MG cells. Biodistribution studies were carried out in mouse xenografts with the subcutaneously induced U87MG tumor. Results: The two radiotracers, 68Ga-NODAGA-AE105 and 68Ga-HBED-CC-AE105 that were prepared in >95% radiochemical yield and >96% radiochemical purity, exhibited excellent in vitro stability. In vivo evaluation studies revealed higher uptake of 68Ga-HBED-CC-AE105 in U87MG tumor as compared to 68Ga-NODAGAAE105; however, increased lipophilicity of 68Ga-HBED-CC-AE105 resulted in slower clearance from blood and other non-target organs. The uPAR specificity of the two radiotracers was ascertained by significant (p<0.05) reduction in the tumor uptake with a co-injected blocking dose of unlabeled AE-105 peptide. Conclusion: Amongst the two radiotracers studied, the neutral 68Ga-NODAGA-AE105 with more hydrophilic chelator exhibited faster clearance from non-target organs. The conjugation of HBED-CC chelator (less hydrophilic) resulted in negatively charged 68Ga-HBED-CC-AE105 which was observed to have high retention in blood that decreased target to non-target ratios.

scholarly journals 2-Nitroimidazole-Furanoside Derivatives for Hypoxia Imaging—Investigation of Nucleoside Transporter Interaction, 18F-Labeling and Preclinical PET Imaging

2019 ◽  
Vol 12 (1) ◽  
pp. 31
Author(s):  
Florian Maier ◽  
Anna Schweifer ◽  
Vijaya Damaraju ◽  
Carol Cass ◽  
Gregory Bowden ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Tumor Hypoxia ◽  
Radiochemical Yield ◽  
Nucleoside Transporters ◽  
Nucleoside Transporter ◽  
Hypoxia Imaging ◽  
Molar Activity ◽  
Slow Kinetics ◽  
Sugar Derivatives

The benefits of PET imaging of tumor hypoxia in patient management has been demonstrated in many examples and with various tracers over the last years. Although, the optimal hypoxia imaging agent has yet to be found, 2-nitroimidazole (azomycin) sugar derivatives—mimicking nucleosides—have proven their potential with [18F]FAZA ([18F]fluoro-azomycin-α-arabinoside) as a prominent representative in clinical use. Still, for all of these tracers, cellular uptake by passive diffusion is postulated with the disadvantage of slow kinetics and low tumor-to-background ratios. We recently evaluated [18F]fluoro-azomycin-β-deoxyriboside (β-[18F]FAZDR), with a structure more similar to nucleosides than [18F]FAZA and possible interaction with nucleoside transporters. For a deeper insight, we comparatively studied the interaction of FAZA, β-FAZA, α-FAZDR and β-FAZDR with nucleoside transporters (SLC29A1/2 and SLC28A1/2/3) in vitro, showing variable interactions of the compounds. The highest interactions being for β-FAZDR (IC50 124 ± 33 µM for SLC28A3), but also for FAZA with the non-nucleosidic α-configuration, the interactions were remarkable (290 ± 44 µM {SLC28A1}; 640 ± 10 µM {SLC28A2}). An improved synthesis was developed for β-FAZA. For a PET study in tumor-bearing mice, α-[18F]FAZDR was synthesized (radiochemical yield: 15.9 ± 9.0% (n = 3), max. 10.3 GBq, molar activity > 50 GBq/µmol) and compared to β-[18F]FAZDR and [18F]FMISO, the hypoxia imaging gold standard. We observed highest tumor-to-muscle ratios (TMR) for β-[18F]FAZDR already at 1 h p.i. (2.52 ± 0.94, n = 4) in comparison to [18F]FMISO (1.37 ± 0.11, n = 5) and α-[18F]FAZDR (1.93 ± 0.39, n = 4), with possible mediation by the involvement of nucleoside transporters. After 3 h p.i., TMR were not significantly different for all 3 tracers (2.5–3.0). Highest clearance from tumor tissue was observed for β-[18F]FAZDR (56.6 ± 6.8%, 2 h p.i.), followed by α-[18F]FAZDR (34.2 ± 7.5%) and [18F]FMISO (11.8 ± 6.5%). In conclusion, both isomers of [18F]FAZDR showed their potential as PET hypoxia tracers. Differences in uptake behavior may be attributed to a potential variable involvement of transport mechanisms.

scholarly journals Preclinical Evaluation and Pilot Clinical Study of Al18F-DX600-BCH for non-invasive PET Mapping of Angiotensin Converting Enzyme 2 in Mammal

2021 ◽  
Author(s):  
Jin Ding ◽  
Qian Zhang ◽  
Jinquan Jiang ◽  
Nina Zhou ◽  
Zilei Wang ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Pet Imaging ◽  
Transmembrane Protein ◽  
Radiochemical Yield ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Non Invasive ◽  
Pet Ct ◽  
Pilot Clinical Study

Abstract Angiotensin-converting enzyme 2 (ACE2), a transmembrane protein, is the main entry point for certain coronaviruses including the new coronavirus SARS-CoV-2 to enter cells. Synthesizing the PET imaging probe Al18F-DX600-BCH which is high-affinity ACE2 is aim to detect the expression of ACE2 in body and monitor the therapeutic effect. The Al18F-DX600-BCH was obtained manually with a 20.4% ± 5.2% radiochemical yield without attenuation correction and an over 99% purified radiochemical purity, being stable in vitro within 4 hours and cleared rapidly in blood (the half-lives of the distribution phase and clearance phase were 2.12 min and 25.31 min, respectively). Results of both biodistribution and PET imaging showed that Al18F-DX600-BCH was highly accumulated in the kidney (SUVkidney/normal > 50), and specific uptake in testis (SUVtestis/normal > 10) was observed in rat images. The kidney (++), gastrointestinal (++) and bronchial (+++) cells were evidenced of ACE2 positive by IHC staining of rats. A total of 10 volunteers were enrolled and received PET/CT 1 hour and 2 hours after injection or dynamic PET/CT during 0-330 seconds (NCT04542863), from which strong radioactivity accumulation was mostly observed in the genitourinary system (SUVrenal cortex = 32.00, SUVtestis = 4.56), and moderate accumulation in conjunctiva and nasal mucosa for several cases. This work firstly reported the probe Al18F-DX600-BCH targeting ACE2, conducting preliminary preclinical experiments and a total of 10 clinical transformations, which demonstrated the potential and possibility of non-invasive mapping of ACE2. Trial registration: ClinicalTrials.gov NCT04542863. Registered 9 September 2020.

scholarly journals Evaluation of Radioiodinated Fluoronicotinamide/Fluoropicolinamide-Benzamide Derivatives as Theranostic Agents for Melanoma

2020 ◽  
Vol 21 (18) ◽  
pp. 6597
Author(s):  
Chao-Cheng Chen ◽  
Yang-Yi Chen ◽  
Yi-Hsuan Lo ◽  
Ming-Hsien Lin ◽  
Chih-Hsien Chang ◽  
...  
Keyword(s):  
Absorbed Dose ◽  
Radiochemical Yield ◽  
Amelanotic Melanoma ◽  
In Vivo Studies ◽  
Log P ◽  
Theranostic Agent ◽  
Biodistribution Studies ◽  
Theranostic Agents

Malignant melanoma is the most harmful type of skin cancer and its incidence has increased in this past decade. Early diagnosis and treatment are urgently desired. In this study, we conjugated picolinamide/nicotinamide with the pharmacophore of 131I-MIP-1145 to develop 131I-iodofluoropicolinamide benzamide (131I-IFPABZA) and 131I-iodofluoronicotiamide benzamide (131I-IFNABZA) with acceptable radiochemical yield (40 ± 5%) and high radiochemical purity (>98%). We also presented their biological characteristics in melanoma-bearing mouse models. 131I-IFPABZA (Log P = 2.01) was more lipophilic than 131I-IFNABZA (Log P = 1.49). B16F10-bearing mice injected with 131I-IFNABZA exhibited higher tumor-to-muscle ratio (T/M) than those administered with 131I-IFPABZA in planar γ-imaging and biodistribution studies. However, the imaging of 131I-IFNABZA- and 131I-IFPABZA-injected mice only showed marginal tumor uptake in A375 amelanotic melanoma-bearing mice throughout the experiment period, indicating the high binding affinity of these two radiotracers to melanin. Comparing the radiation-absorbed dose of 131I-IFNABZA with the melanin-targeted agents reported in the literature, 131I-IFNABZA exerts lower doses to normal tissues on the basis of similar tumor dose. Based on the in vitro and in vivo studies, we clearly demonstrated the potential of using 131I-IFNABZA as a theranostic agent against melanoma.

scholarly journals Automated Synthesis of18F-Fluoropropoxytryptophan for Amino Acid Transporter System Imaging

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
I-Hong Shih ◽  
Xu-Dong Duan ◽  
Fan-Lin Kong ◽  
Michael D. Williams ◽  
Kevin Yang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cellular Uptake ◽  
Pet Imaging ◽  
Lung Tumor ◽  
Radiochemical Yield ◽  
Small Cell ◽  
Cancer Model ◽  
Imaging Studies ◽  
Small Cell Lung

Objective. This study was to develop a cGMP grade of [18F]fluoropropoxytryptophan (18F-FTP) to assess tryptophan transporters using an automated synthesizer.Methods. Tosylpropoxytryptophan (Ts-TP) was reacted with K18F/kryptofix complex. After column purification, solvent evaporation, and hydrolysis, the identity and purity of the product were validated by radio-TLC (1M-ammonium acetate : methanol = 4 : 1) and HPLC (C-18 column, methanol : water = 7 : 3) analyses.In vitrocellular uptake of18F-FTP and18F-FDG was performed in human prostate cancer cells. PET imaging studies were performed with18F-FTP and18F-FDG in prostate and small cell lung tumor-bearing mice (3.7 MBq/mouse, iv).Results. Radio-TLC and HPLC analyses of18F-FTP showed that the Rf and Rt values were 0.9 and 9 min, respectively. Radiochemical purity was >99%. The radiochemical yield was 37.7% (EOS 90 min, decay corrected). Cellular uptake of18F-FTP and18F-FDG showed enhanced uptake as a function of incubation time. PET imaging studies showed that18F-FTP had less tumor uptake than18F-FDG in prostate cancer model. However,18F-FTP had more uptake than18F-FDG in small cell lung cancer model.Conclusion.18F-FTP could be synthesized with high radiochemical yield. Assessment of upregulated transporters activity by18F-FTP may provide potential applications in differential diagnosis and prediction of early treatment response.

scholarly journals Galectin-3 is an important mediator of VEGF- and bFGF-mediated angiogenic response

2010 ◽  
Vol 207 (9) ◽  
pp. 1981-1993 ◽  
Author(s):  
Anna I. Markowska ◽  
Fu-Tong Liu ◽  
Noorjahan Panjwani
Keyword(s):  
Growth Factor ◽  
Binding Protein ◽  
Integrin Αvβ3 ◽  
Dominant Negative ◽  
Carbohydrate Binding ◽  
Αvβ3 Integrin ◽  
Angiogenic Response ◽  
Inhibition Of Angiogenesis ◽  
Galectin 3

Recent studies have shown that a carbohydrate-binding protein, galectin-3, is a novel pro-angiogenic molecule. The mechanism by which galectin-3 promotes angiogenesis remains unknown. We demonstrate here that galectin-3 is a mediator of vascular endothelial growth factor (VEGF)- and basic fibroblast growth factor (bFGF)-mediated angiogenic response. Angiogenesis assays revealed that galectin-3 inhibitors, β-lactose and dominant-negative galectin-3, reduce VEGF- and bFGF-mediated angiogenesis in vitro and that VEGF- and bFGF-mediated angiogenic response is reduced in galectin-3 knockdown cells and Gal3−/− animals. Integrin αvβ3 was identified as the major galectin-3–binding protein and anti-αv, -β3, and -αvβ3 integrin function-blocking antibodies significantly inhibited the galectin-3–induced angiogenesis. Furthermore, galectin-3 promoted the clustering of integrin αvβ3 and activated focal adhesion kinase. Knockdown of GnTV, an enzyme that synthesizes high-affinity glycan ligands for galectin-3, substantially reduced: (a) complex N-glycans on αvβ3 integrins and (b) VEGF- and bFGF-mediated angiogenesis. Collectively, these data suggest that galectin-3 modulates VEGF- and bFGF-mediated angiogenesis by binding via its carbohydrate recognition domain, to the GnTV synthesized N-glycans of integrin αvβ3, and subsequently activating the signaling pathways that promote the growth of new blood vessels. These findings have broad implications for developing novel, carbohydrate-based therapeutic agents for inhibition of angiogenesis.

scholarly journals Cyclic RGD and isoDGR Integrin Ligands Containing cis-2-amino-1-cyclopentanecarboxylic (cis-β-ACPC) Scaffolds

Molecules ◽  
2020 ◽  
Vol 25 (24) ◽  
pp. 5966
Author(s):  
Silvia Panzeri ◽  
Daniela Arosio ◽  
Silvia Gazzola ◽  
Laura Belvisi ◽  
Monica Civera ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Solid Phase ◽  
Integrin Αvβ3 ◽  
Adhesion Assay ◽  
Αvβ3 Integrin ◽  
Binding Assays ◽  
Docking Simulations ◽  
Ic50 Values ◽  
Integrin Ligands

Integrin ligands containing the tripeptide sequences Arg-Gly-Asp (RGD) and iso-Asp-Gly- Arg (isoDGR) were actively investigated as inhibitors of tumor angiogenesis and directing unit in tumor-targeting drug conjugates. Reported herein is the synthesis, of two RGD and one isoDGR cyclic peptidomimetics containing (1S,2R) and (1R,2S) cis-2-amino-1-cyclopentanecarboxylic acid (cis-β-ACPC), using a mixed solid phase/solution phase synthetic protocol. The three ligands were examined in vitro in competitive binding assays to the purified αvβ3 and α5β1 receptors using biotinylated vitronectin (αvβ3) and fibronectin (α5β1) as natural displaced ligands. The IC50 values of the ligands ranged from nanomolar (the two RGD ligands) to micromolar (the isoDGR ligand) with a pronounced selectivity for αvβ3 over α5β1. In vitro cell adhesion assays were also performed using the human skin melanoma cell line WM115 (rich in integrin αvβ3). The two RGD ligands showed IC50 values in the same micromolar range as the reference compound (cyclo[RGDfV]), while for the isoDGR derivative an IC50 value could not be measured for the cell adhesion assay. A conformational analysis of the free RGD and isoDGR ligands by NMR (VT-NMR and NOESY experiments) and computational studies (MC/EM and MD), followed by docking simulations performed in the αVβ3 integrin active site, provided a rationale for the behavior of these ligands toward the receptor.

scholarly journals Synthesis and Preclinical Evaluation of 68Ga-MALAT-1 ASO for PET Imaging of MALAT-1 expressing Tumours

2020 ◽  
Author(s):  
Zhen-Feng Liu ◽  
Jun Yang ◽  
Qianni Ye ◽  
Min Yang ◽  
Dong-hui Pan ◽  
...  
Keyword(s):  
Noncoding Rna ◽  
Malignant Tumors ◽  
Radiochemical Yield ◽  
Cell Uptake ◽  
Log P ◽  
Pharmacokinetic Studies ◽  
Specific Uptake ◽  
Pet Scans

Abstract Background: MALAT-1 (Metastasis-Associated Lung Adenocarcinoma Transcript 1) is a large long nuclear noncoding RNA (lncRNA) that is overexpressed in an array of cancers. In this study, we designed a range of positron probes for MALAT-1 to evaluate its distribution, pharmacokinetics, and to explore whether the probe can be used for the imaging of malignant tumors with high MALAT-1 expression in vivo. Methods: 68Ga labelling of MALAT-1 antisense oligonucleotides (68Ga–MALAT-1 ASO) was synthesized by the conjugation of MALAT-1 NOTA-ASO and 68Ga3+. Purity was assessed by radio-HPLC. Pharmacokinetic studies and cell uptake were assessed. The biodistribution and metabolism of 68Ga–MALAT-1 ASO in normal ICR and MHCC-LM3 xenograft-bearing nude mice were studied. Results: 68Ga–MALAT-1 ASO was obtained at a radiochemical yield of 98% from a 10 min synthesis with 100 ± 50 MBq/nmol activity and > 99% purity once synthesized. The Log P was -2.53±0.19. The tracer displayed excellent stability in vitro. 68Ga–MALAT-1 ASO showed satisfactory binding ability to MHCC-LM3 cells; the biodistribution of 68Ga-MALAT-1 ASO in MHCC-LM3 tumour-bearing mice showed high levels of uptake (3.04 ± 0.11%ID/g). Micro-PET scans demonstrated the tumor specific uptake of 68Ga-MALAT-1 ASO in mouse models. Conclusions: We conclude that 68Ga labelling of MALAT-1 ASO is a convenient approach to label tumors overexpressing MALAT-1.

Synthesis and Characterization of ROSA Dye - A Rhodamine B-type Fluorophore, Suitable for Bioconjugation and Fluorescence Studies in Live Cells

2019 ◽  
Vol 26 (10) ◽  
pp. 758-767
Author(s):  
Vicente Rubio ◽  
Vijaya Iragavarapu ◽  
Maciej J. Stawikowski
Keyword(s):  
Quantum Yield ◽  
Cancer Cells ◽  
Fluorescent Probe ◽  
Extinction Coefficient ◽  
Rhodamine B ◽  
Solid Phase ◽  
Total Yield ◽  
Molar Extinction Coefficient ◽  
Αvβ3 Integrin ◽  
Αvβ3 Integrins

Background: Herein we report the multigram-scale synthesis, characterization and application of a rhodamine B-based fluorophore (ROSA) suitable for fluorescent studies in biological applications. This fluorophore is devoid of rhodamine spirolactone formation and furthermore characterized by a high molar extinction coefficient (ϵ=87250 ± 1630 M-1cm-1) and quantum yield (φ) of 0.589 ± 0.070 in water. Reported here is also the application of ROSA towards synthesis of a ROSA-PEG-GRGDS-NH2 fluorescent probe suitable for live cell imaging of αvβ3 integrins for in vitro assays. Objective: The main objective of this study is to efficiently prepare rhodamine B derivative, devoid of spirolactone formation that would be suitable for bioconjugation and subsequent bioimaging. Methods: Rhodamine B was transformed into rhodamine B succinimide ester (RhoB-OSu) using N-hydroxysuccinimide. RhoB-OSu was further coupled to sarcosine to obtain rhodamine Bsarcosine dye (ROSA) in good yield. The ROSA dye was then coupled to a αvβ3 integrin binding sequence using standard solid-phase conditions. Resulting ROSA-PEG-GRGDS-NH2 probe was used to image integrins on cancer cells. Results: The rhodamine B-sarcosine dye (ROSA) was obtained in multigram scale in good total yield of 47%. Unlike rhodamine B, the ROSA dye does not undergo pH-dependent spirolactone/spirolactam formation as compared with rhodamine B-glycine. It is also characterized by excellent quantum yield (φ) of 0.589 ± 0.070 in water and high molar extinction coefficient of 87250 ± 1630 M-1cm-1. ROSA coupling to the RGD-like peptide was proved to be efficient and straightforward. Imaging using standard filters on multimode plate reader and confocal microscope was performed. The αvβ3 integrins present on the surface of live WM-266-4 (melanoma) and MCF- 7 (breast cancer) cells were successfully imaged. Conclusion: We successfully derivatized rhodamine B to create an inexpensive, stable and convenient to use fluorescent probe. The obtained derivative has excellent photochemical properties and it is suitable for bioconjugation and many imaging applications.

Radiolabeled Peptide Probes for Liver Cancer Imaging

2020 ◽  
Vol 27 (41) ◽  
pp. 6968-6986
Author(s):  
Rui Cao ◽  
Hongguang Liu ◽  
Zhen Cheng
Keyword(s):  
Liver Cancer ◽  
Cancer Diagnosis ◽  
Cancer Imaging ◽  
Growth Factor Receptor ◽  
Targeted Imaging ◽  
Cancer Death ◽  
Binding Properties ◽  
Radiolabeled Peptides ◽  
Epidermal Growth ◽  
Peptide Probes

Liver cancer/Hepatocellular Carcinoma (HCC) is a leading cause of cancer death and represents an important cause of mortality worldwide. Several biomarkers are overexpressed in liver cancer, such as Glypican 3 (GPC3) and Epidermal Growth Factor Receptor (EGFR). These biomarkers play important roles in the progression of tumors and could serve as imaging and therapeutic targets for this disease. Peptides with adequate stability, receptor binding properties, and biokinetic behavior have been intensively studied for liver cancer imaging. A great variety of them have been radiolabeled with clinically relevant radionuclides for liver cancer diagnosis, and many are promising imaging and therapeutic candidates for clinical translation. Herein, we summarize the advancement of radiolabeled peptides for the targeted imaging of liver cancer.

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