sodium-pertechnetate-tc-99m and Carcinoma--Hepatocellular

The aim of this phase II study was to assess the clinical utility and safety of AFP-Scan (Immunomedics, Inc, Morris Plains, NJ), a technetium-99m (99mTc)-labeled anti-alpha-fetoprotein (AFP) Fab' imaging kit, in the evaluation of hepatocellular carcinoma (HCC), in comparison to computed tomography (CT).. Twenty-five consecutive patients with a history of HCC were examined by planar and single-photon emission computed tomography (SPECT) imaging at 6 and 24 hours after intravenous (I.V.) injection of 1 mg AFP-Scan labeled with 925 MBq 99mTc.. In 20 patients, there was a specific binding of the Fab' antibody to the tumor, whereas in four patients who presented with elevated serum AFP levels, no specific targeting was found and no malignant lesions were evident by CT or biopsy. One patient was diagnosed as false-negative by AFP-Scan. In five of six patients with normal serum AFP levels, focal uptake was demonstrated. In one case, metastatic disease in the lower abdomen was found. In all patients, diagnostically relevant information was provided by the 24-hour antibody images, especially with SPECT. Comparing AFP-Scan versus CT, the former showed a higher sensitivity (95% v 63%) and specificity (67% v 17%), with an overall accuracy of 88% versus 52% for AFP-Scan versus CT, even in patients with normal serum AFP titers. No adverse reactions or human antimouse antibody (HAMA) elevations were found in any of the patients.. AFP-Scan appears to be a promising new antibody imaging kit for the disclosure of sites of HCC and should aid in the management of these patients by revealing primary, recurrent, and metastatic disease with a single imaging modality.

Topics: Adult; Aged; Aged, 80 and over; alpha-Fetoproteins; Antibodies, Neoplasm; Carcinoma, Hepatocellular; Female; Humans; Liver Neoplasms; Male; Middle Aged; Predictive Value of Tests; Radiopharmaceuticals; Reagent Kits, Diagnostic; Sodium Pertechnetate Tc 99m; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed

We report the synthesis, in vitro and in vivo investigation of folate-targeted, biocompatible, biodegradable self-assembled nanoparticles radiolabelled with (99m)Tc, as potential new SPECT or SPECT/CT imaging agent. Nanoparticles with hydrodynamic size in the range of 75-200 nm were prepared by self-assembly of chitosan and folated poly-γ-glutamic acid, and then radiolabelled with (99m)Tc. The nanoparticles target tumour cells overexpressing folate receptors and internalize specifically into them to realize early tumour diagnosis detected by SPECT and SPECT/CT modalities. Rat hepatocellular carcinoma cells were used as model system. Cell specificity and tumour targeting efficacy of these nanosystems were investigated in vitro, and in vivo using SPECT and fusion nanoSPECT/CT imaging. In vitro results showed that the radiolabeled nanosystem was efficiently internalized by tumour cells. Whole-body biodistribution of the new radiolabelled, folate-targeted nanoparticles revealed higher uptake in the tumorous kidney compared to the non-tumorous contralateral side. Uptake by the lungs and thyroids was negligible, which confirmed the stability of the nanoparticles in vivo. In vivo SPECT and SPECT/CT imaging visually reinforced the uptake results and were in accordance with the biodistribution data: the new nanoparticles as a targeted contrast agent improve tumour targeting and are able to detect folate-receptor-overexpressing tumours in animal models with enhanced contrast.

Topics: Animals; Carcinoma, Hepatocellular; Chitosan; Folate Receptors, GPI-Anchored; Liver Neoplasms; Male; Nanoparticles; Particle Size; Radiopharmaceuticals; Rats; Rats, Inbred F344; Sodium Pertechnetate Tc 99m; Tissue Distribution; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed

The purpose of this study was to investigate the anticancer effects of combined RNA interference (RNAi) of the adenine nucleotide translocase-2 (ANT2) gene and ganciclovir (GCV) therapy for treatment of hepatocellular carcinoma cells (Huh 7) in an animal model.. The Huh 7/NTG stable cell line was established by transfection of a vector with the human sodium iodide symporter (hNIS), HSV1-sr39 thymidine kinase (tk), and enhanced green florescent protein (EGFP) fusion gene into Huh 7 cells. mRNA expressions of these genes were evaluated by RT-PCR analysis. The functions of hNIS and HSV1-sr39tk were verified with (125)I uptake and (3)H-penciclovir (PCV) uptake tests. EGFP and hNIS expression was confirmed with confocal microscopy after immunocytochemical staining. We treated the tumor cells with ANT2 shRNA or GCV or both ANT2 shRNA and GCV and treated the in vivo mouse model with a Huh 7/NTG tumor xenograft. The therapeutic effects of the in vivo study were assessed with caliper measurements and gamma camera imaging using (99m)Tc-pertechnetate.. Huh 7/NTG cells showed a cell number-dependent increase in (125)I uptake and a 24-fold higher (3)H-PCV uptake compared to parent Huh 7 cells. Huh 7/NTG cells transfected with ANT2 shRNA had lower ANT2 mRNA expression and more impaired proliferation activity than cells transfected with scramble shRNA. Proliferation of Huh 7/NTG cells was also inhibited by GCV treatment. Combined GCV and ANT2 shRNA therapy further inhibited cell proliferation in the in vitro study. The combined therapy with GCV and ANT2 shRNA showed a further decrease in tumor growth in the mouse model.. Our results suggest that the combined RNA interference with ANT2 and GCV therapy inhibited hepatocellular carcinoma cell proliferation more than single GCV therapy or ANT2 shRNA therapy in vitro and in vivo. Therefore it could be applied treating incurable hepatocellular carcinoma.

Topics: Adenine Nucleotide Translocator 2; Animals; Biological Transport; Carcinoma, Hepatocellular; Cell Line, Tumor; Cell Survival; Cell Transformation, Neoplastic; Ganciclovir; Herpesvirus 1, Human; Humans; Liver Neoplasms; Mice; Prodrugs; Radionuclide Imaging; RNA Interference; Sodium Pertechnetate Tc 99m; Thymidine Kinase

The aim of the study is evaluation of the possible role of the scintigraphic estimation of the relative liver perfusion in diagnosis and the choice of treatment of liver carcinomas.. Hepatic perfusion index was obtained by dynamic scintigraphy in 126 patients.. In the control group values did not differ from the value in the patients with benign tumors (p > 0.05). However, in hepatocellular carcinoma and liver metastases of different tumors, HPI values were significantly decreased in comparison to controls and benign tumors (p < 0.01), but they didn't differ between themselves (p > 0.05). The values were especially low in the patients with malignant diseases in the liver accosciated with vascular disturbances in the portal system.. HRA could be easily done during the different conventional nuclear medicine methods. It can be an useful method for the assessment of different degrees of hemodynamic alterations in portal system, for differential diagnosis of benign and malignant liver tumors, as well as for assessment of the liver tissue and tumor perfusion, which might be helpful in the decision making for the undertaking of intraarterial (radionuclide, chemotherapy etc.) therapy.

Topics: Carcinoma, Hepatocellular; Humans; Liver Circulation; Liver Neoplasms; Portal Vein; Radionuclide Angiography; Radiopharmaceuticals; Sodium Pertechnetate Tc 99m

The behavior of an anti-cancer drug consisting of transcatheter hepatic segmental arterial chemoembolization using Lipiodol mixed with an anti-cancer drug followed by gelatin sponge (segmental Lp-TAE: Seg-Lp-TAE) was assessed in comparison to that of the non-segmental Lp-TAE to whole liver (Lp-TAE) by means of Tc-99m pertechnetate (RI). Injection of Lipiodol mixed with Adriamycin and 740 mBq of RI followed by gelatin sponge was carried out from segmental or subsegmental hepatic artery in 12 cases of hepatocellular carcinoma and from proper or right hepatic artery in 11 cases (9 with hepatocellular carcinoma and 2 with metastatic liver tumor). The distribution and retention of RI were studied from the time activity curves of ROIs in tumor and non-tumor area, and scintigrams at 4 and 24 hours after injection. The integral value ratio of tumor to non-tumor was significantly higher in Seg-Lp-TAE, indicating that es the distribution of RI after Seg-Lp-TAE is selective in the segments where tumor exists. In Seg-Lp-TAE, the T1/2 was higher and the count ratio of tumor to non-tumor was significantly higher at 4 hours and even higher at 24 hours after injection. These results suggest that an anti-cancer drug reinforces the effect on tumor with little adverse effect on normal liver in Seg-Lp-TAE, which is more advantageous to the treatment of hepatocellular carcinoma.

Topics: Antineoplastic Agents; Carcinoma, Hepatocellular; Embolization, Therapeutic; Gelatin Sponge, Absorbable; Hepatic Artery; Humans; Infusions, Intra-Arterial; Iodized Oil; Liver; Liver Neoplasms; Male; Middle Aged; Radionuclide Imaging; Sodium Pertechnetate Tc 99m

Evaluation of "Gianturco-Wallace chemotherapy pulser," which was developed to produce a more homogeneous drug distribution of the tumors in intra-arterial infusion chemotherapy, was assessed by comparative study of pulsed and nonpulsed arterial radionuclide infusion using Tc-99m pertechnetate for 18 cases of hepatic carcinomas (11 cases of hepatocellular carcinomas and 7 cases of metastatic hepatic carcinomas). Tc-99m pertechnetate, 740 MBq (20 mCi) diluted with saline (30 mL) was infused with or without pulse through the catheter into the hepatic artery at a rate of 1mL per minute. The intrahepatic dynamic radionuclide distribution was analyzed by the time activity curves of ROIs in the tumor and nontumor areas. Pulsed infusion interrupted laminar flow and produced more homogeneous radionuclide distribution in the liver, and combination of pulsed and nonpulsed infusion also produced better radionuclide distribution in the areas of the tumors. This method using Tc-99m pertechnetate was very useful as a simulation to determine the dynamic drug distribution of the tumor and non-tumor region in intraarterial infusion methods.

Topics: Antineoplastic Agents; Carcinoma, Hepatocellular; Hepatic Artery; Humans; Infusions, Intra-Arterial; Liver; Liver Neoplasms; Male; Middle Aged; Pulsatile Flow; Radionuclide Imaging; Sodium Pertechnetate Tc 99m; Tissue Distribution

Topics: Antineoplastic Agents; Carcinoma, Hepatocellular; Doxorubicin; Embolization, Therapeutic; Humans; Iodized Oil; Liver Neoplasms; Male; Metabolic Clearance Rate; Middle Aged; Sodium Pertechnetate Tc 99m

Radionuclide flow studies, planar, and SPECT hepatic blood pool imaging were performed in 23 patients with 39 hepatic hemangiomas, 23 patients with primary and secondary liver tumors, 12 patients with hepatocellular disease, two patients with hepatic cysts, and 10 patients with no evidence of liver disease. The hepatic SPECT imaging identified all 39 hemangiomas as having a sequestration pattern compared with a yield of 69% (27 of 39 cases) for the planar imaging. None of the 47 other patients demonstrated this pattern. The SPECT approach is considered superior to planar blood pool imaging because of improved diagnostic yield, reduced patient imaging time, and greater ease of correlation with other cross-sectional imaging modalities.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Hepatocellular; Diagnosis, Differential; Erythrocytes; Female; Hemangioma; Humans; Liver; Liver Neoplasms; Male; Middle Aged; Sodium Pertechnetate Tc 99m; Tomography, Emission-Computed

Thirteen patients with a history of confirmed liver carcinoma were given either I131 goat polyclonal or murine monoclonal antibodies against alpha-fetoprotein (AFP), and then scanned with a gamma camera. In order to reduce background, nontarget activity, especially in the liver, blood pool, and reticuloendothelial system, 99mTc imaging agents were used for tumor image enhancement by computer-assisted subtraction. A sensitivity of 91% for the primary site, 50% for the lungs (33% for the chest area), and 75% for the abdomen and pelvis was achieved, with a specificity of 100%, 94%, and 100% for these sites, respectively. The accuracy was determined to be 93% for the liver, 86% for the lungs (77% for the chest), and 85% for the abdominal and pelvic area, resulting in an overall accuracy rate for imaging primary and metastatic hepatocellular cancer of 84% (90% if bone metastases are excluded). In two of the 13 patients, lesions that had been missed by conventional liver scintigraphy and transmission computed tomography (CT) were first shown by radioimmunodetection (RAID).

Topics: Abdominal Neoplasms; Adult; alpha-Fetoproteins; Antibodies; Antibodies, Monoclonal; Carcinoma, Hepatocellular; Child, Preschool; Female; Hemangiosarcoma; Humans; Image Enhancement; Image Processing, Computer-Assisted; Liver Neoplasms; Male; Pelvic Neoplasms; Radionuclide Imaging; Sodium Pertechnetate Tc 99m; Technetium Tc 99m Aggregated Albumin; Technetium Tc 99m Sulfur Colloid; Thoracic Neoplasms

To determine the accuracy of blood-pool imaging in the diagnosis of hepatic hemangiomas, 39 patients with various focal hepatic lesions were studied. The diagnoses in these patients were made by biopsy, angiography, surgical exploration, or clinical stability for a minimum of 14 months. The diagnoses were: hemangiomas (13 patients), hepatoma (three), metastases (19), abscesses (two), and liver cysts (two). After modified in vivo labeling of red blood cells with 20 mCi (740 MBq) of 99mTc pertechnetate, an initial flow study and early (1-15 min) and delayed (1-2 hr) static images were obtained. Increased blood-pool activity with a discordant flow pattern was seen in 11 of 13 patients with hemangiomas. False-negative scans occurred in two hemangiomas with extensive fibrosis. Two of three hepatomas had increased blood-pool activity associated with increased flow in a pattern identical to the increased blood-pool activity. None of the metastatic, abscess, or cystic lesions had increased blood-pool activity at any time after injection. It is concluded that 99mTc red blood cell imaging can distinguish hemangiomas from other focal liver lesions.

Topics: Adult; Aged; Carcinoma, Hepatocellular; Cysts; Diagnosis, Differential; Erythrocytes; Female; Hemangioma; Humans; Liver Abscess; Liver Diseases; Liver Neoplasms; Male; Middle Aged; Radionuclide Imaging; Sodium Pertechnetate Tc 99m; Technetium