Radiation dosimetry of 99mTc-labeled C225 in patients with squamous cell carcinoma of the head and neck.

This study assessed the radiation dosimetry of 99mTc-labeled ethylene dicysteine (EC) C225 (EC-C225), a promising radioligand for functional tumor imaging. METHODS: Whole-body scanning was performed on 6 patients with head and neck squamous cell carcinoma up to 24 h after administration of 99mTc-EC-C225. Alternate patients who had been randomized to receive C225 in a phase III trial received 99mTc-EC-C225 before their 20-mg test dose or after their 400 mg/m2 loading dose of unlabeled C225 (patients 1/3/5 and 2/4/6, respectively). Radiation dosimetry was assessed using the MIRD method. RESULTS: The critical organ was the kidney, with an average radiation-absorbed dose for all 6 patients of 0.0274 mGy/MBq. The average total-body absorbed dose was 0.0022 mGy/MBq (0.243 cGy/1,110 MBq). CONCLUSION: The new radiopharmaceutical 99mTc-EC-C225 appears to have reasonable dosimetric properties for a diagnostic nuclear medicine agent. Correlation of the imaging results with clinical findings is the next step.     

PEGylated N-methyl-S-methyl dithiocarbazate as a new reagent for the high-yield preparation of nitrido Tc-99m and Re-188 radiopharmaceuticals

A novel nitrido nitrogen atom donor for the preparation of ^99mTc and ¹⁸⁸Re radiopharmaceuticals containing a metal-nitrogen multiple bond is presented. HO₂C-PEG₆₀₀-DTCZ was obtained by conjugation of N-methyl-S-methyl dithiocarbazate [H₂N–N(CH₃)–C(S)SCH₃, HDTCZ] with polyethylene glycol 600 (PEG₆₀₀). Asymmetrical heterocomplexes of the type [M(N)(PNP)(B)]^0/+ (M=^99mTc, ¹⁸⁸Re; PNP=diphosphine ligands, B=DBODC, DEDC, NSH, H₂OS, CysNAc, HDTCZ) and symmetrical nitride compounds of the type [M(N)(L)₂] (L=DEDC, DPDC) have been prepared in high yield by using the newly designed nitride nitrogen atom donor HO₂C-PEG₆₀₀-DTCZ. A two-step procedure was applied for preparing the above symmetrical and asymmetrical complexes. The first step involved the preliminary formation of a mixture of nitride Tc-99m or Re-188 precursors, which contained the [MN]²⁺ core, through reduction of generator-eluted ^99mTc-pertechnetate or ¹⁸⁸Re-perrhenate with thin (II) chloride in the presence of HO₂C-PEG₆₀₀-DTCZ. In the second step, the intermediate mixture was converted either in the final mixed asymmetrical complex by the simultaneous addition of diphosphine ligand and the suitable bidentate ligand B, or in the final symmetrical complex by the only addition of the bidentate ligand L. It was also demonstrated that the novel water-soluble nitride nitrogen atom donor HO₂C-PEG₆₀₀-DTCZ did not show coordinating properties toward the MN (^99mTc, ¹⁸⁸Re) core. Biodistribution studies in rats of the hitherto unreported [^99mTc(N)(PNP₃)DTCZ]⁺ and [^99mTc(N)(PNP₅)DTCZ]⁺ complexes showed that they selectively localize in the myocardium of rats with a favourable heart-to-lung and heart-to-liver uptake ratios. In particular, the heart-to-lung and heart-to-liver uptake ratios dramatically increased in the interval between 60 and 120 min postinjection. Hence, the combination of the favourable chemical and biological properties of HO₂C-PEG₆₀₀-DTCZ might confer to this novel compound an important role for the development of new ^99mTc and ¹⁸⁸Re-nitrido radiopharmaceuticals.     

Comparison of 99mTc-labeled phosphate and phosphonate agents for skeletal imaging.

The use of 99mTc-labeled phosphate and phosphonate compounds in place of 18F, 85Sr, and 87Sr for bone scintigraphy has become commonplace throughout the world in a relatively short time. The labeling of polyphosphate with 99mTc 4 years ago, followed rapidly by the introduction of 99mTc-labeled pyrophosphate for skeletal imaging, must therefore be regarded as a major contribution to the practice of diagnostic nuclear medicine. The markedly reduced patient radiation exposure and concomitant increase in photon detection efficiency derived from the more favorable physical decay characteristics of 99mTc led to increased sensitivity and resolution and in turn to improved diagnostic efficacy. The subsequent clinical use of the phosphonate complex 99mTc-HEDP represented a further modification of the same basic approach. Current clinical trials with 99mTc-labeled methylene diphosphonic acid (MDP), which appears to demonstrate enhanced biologic properties for scintigraphy of the osseous structures, is the latest example in this series of refinements. This article compares the technetium-labeled agents already in clinical use and, using animal data, contrasts them with several new multifunctional phosphonates and the novel inorganic compound sodium imidodiphosphate (IDP). In addition, an attempt is made to clarify the conflicting evidence in the nuclear medicine literature regarding the relationship between polyphosphate chain length and skeletal uptake.     

Targeted imaging of gastrin-releasing peptide receptors with 99mTc-EDDA/HYNIC-[Lys3]-bombesin: biokinetics and dosimetry in women

BACKGROUND: The gastrin-releasing peptide receptor (GRP-R) is expressed in several normal human tissues and is overexpressed in various human tumors including breast, prostate, small-cell lung cancer and pancreatic cancer. Recently, 99mTc-EDDA/HYNIC-[Lys]-bombesin (99mTc-HYNIC-BN) was reported as a radiopharmaceutical with high stability in human serum, specific cell GRP-R binding and rapid cell internalization. AIM: The aim of this study was to determine the biokinetics and dosimetry of 99mTc-HYNIC-BN and the feasibility of using this radiopharmaceutical to image GRP-R in four early breast cancer patients and seven healthy women. METHODS: Whole-body images were acquired at 20, 90, 180 min, and 24 h after 99mTc-HYNIC-BN administration. The same regions of interest were drawn around source organs on each time frame and regions of interest were converted to activity (conjugate view counting method). The image sequence was used to extrapolate 99mTc-HYNIC-BN time-activity curves in each organ to calculate the total number of disintegrations (N) that occurred in the source regions. N data were the input for the OLINDA/EXM code to calculate internal radiation dose estimates. RESULTS: 99mTc-HYNIC-BN had a rapid blood clearance with mainly renal excretion. No statistically significant differences (P>0.05) in the radiation-absorbed doses among cancer patients and healthy women were observed. The average equivalent doses (n=11) were 24.8+/-8.8 mSv (kidneys), 7.3+/-1.8 mSv (lungs), 6.5+/-4.0 mSv (breast), 2.0+/-0.3 mSv (pancreas), 1.6+/-0.3 mSv (liver), 1.2+/-0.2 mSv (ovaries), and 1.0+/-0.2 mSv (red marrow). The effective dose was 3.3+/-0.6 mSv. The images showed well-differentiated concentration of 99mTc-HYNIC-BN in cancer mammary tissue. CONCLUSION: All the absorbed doses were comparable with those known for most of the 99mTc studies. 99mTc-HYNIC-BN shows high tumor uptake in breasts with malignant tumors so it is a promising imaging radiopharmaceutical to target site-specific early breast cancer. The results obtained warrant a further clinical study to determine specificity/sensibility of 99mTc-HYNIC-BN.     

Targeted bone marrow irradiation in the conditioning of high-risk leukaemia prior to stem cell transplantation

Disease recurrence following stem cell transplantation (SCT) remains a major problem. Despite the sensitivity of leukaemias to chemotherapy and irradiation, conventional conditioning before SCT is limited by significant organ toxicity. Targeted irradiation of bone marrow and spleen by radioimmunotherapy may provide considerable dose escalation, with limited toxicity to non-target organs. In this study, 27 patients with high-risk or relapsing leukaemia were treated with rhenium-188-labelled CD66a,b,c,e radioimmunoconjugates (188Re-mAb) specific for normal bone marrow in addition to conventional conditioning with high-dose chemotherapy and 12 Gy total body irradiation prior to SCT. A mean activity of 10.2+/-2.1 (range 6.9-15.8) GBq 188Re-mAb was administered intravenously. Acute side-effects were assessed according to the CTC classification and patient outcome was determined. Mean radiation doses (Gy; range in parentheses) to relevant organs and whole body were as follows: 13.1 (6.5-22) to bone marrow, 11.6 (1.7-31.1) to spleen, 5.0 (2.0-11.7) to liver, 7.0 (2.3-11.6) to kidneys, 0.7 (0.3-1.3) to lungs and 1.4 (0.8-2.1) to the whole body. Stem cells engrafted in all patients within 9-18 days post SCT. Acute organ toxicity of grade II or less was observed. During follow-up for 25.4+/-5.3 (range 18-34) months, 4/27 (15%) patients died from relapse, and 9/27 (33%) from transplantation-related complications. Fourteen patients (52%) are still alive and in ongoing complete clinical remission. Radioimmunotherapy with the bone marrow-seeking 188Re-labelled CD66 mAb can double the dose to bone marrow and spleen without undue extramedullary acute organ toxicity, when given in addition to high-dose chemotherapy and 12 Gy TBI before allogeneic SCT. This intensified conditioning regimen may reduce the relapse rate of high-risk leukaemia.     

Targeted bone marrow irradiation in the conditioning of high-risk leukaemia prior to stem cell transplantation

Disease recurrence following stem cell transplantation (SCT) remains a major problem. Despite the sensitivity of leukaemias to chemotherapy and irradiation, conventional conditioning before SCT is limited by significant organ toxicity. Targeted irradiation of bone marrow and spleen by radioimmunotherapy may provide considerable dose escalation, with limited toxicity to non-target organs. In this study, 27 patients with high-risk or relapsing leukaemia were treated with rhenium-188-labelled CD66a,b,c,e radioimmunoconjugates (¹⁸⁸Re-mAb) specific for normal bone marrow in addition to conventional conditioning with high-dose chemotherapy and 12 Gy total body irradiation prior to SCT. A mean activity of 10.2DŽ.1 (range 6.9-15.8) GBq ¹⁸⁸Re-mAb was administered intravenously. Acute side-effects were assessed according to the CTC classification and patient outcome was determined. Mean radiation doses (Gy; range in parentheses) to relevant organs and whole body were as follows: 13.1 (6.5-22) to bone marrow, 11.6 (1.7-31.1) to spleen, 5.0 (2.0-11.7) to liver, 7.0 (2.3-11.6) to kidneys, 0.7 (0.3-1.3) to lungs and 1.4 (0.8-2.1) to the whole body. Stem cells engrafted in all patients within 9-18 days post SCT. Acute organ toxicity of grade II or less was observed. During follow-up for 25.4LJ.3 (range 18-34) months, 4/27 (15%) patients died from relapse, and 9/27 (33%) from transplantation-related complications. Fourteen patients (52%) are still alive and in ongoing complete clinical remission. Radioimmunotherapy with the bone marrow-seeking ¹⁸⁸Re-labelled CD66 mAb can double the dose to bone marrow and spleen without undue extramedullary acute organ toxicity, when given in addition to high-dose chemotherapy and 12 Gy TBI before allogeneic SCT. This intensified conditioning regimen may reduce the relapse rate of high-risk leukaemia.     

99mTc-labeled interleukin 8 for the scintigraphic detection of infection and inflammation: first clinical evaluation.

Interleukin 8 (IL-8) is a chemotactic cytokine that binds with a high affinity to receptors expressed on neutrophils. Previous studies with various animal models showed that (99m)Tc-labeled IL-8 accumulates specifically and rapidly in infectious and inflammatory foci. The aims of the present study were to evaluate the safety of IL-8 in humans and to assess the value of (99m)Tc-IL-8 scintigraphy in patients with suspected localized infections. METHODS: (99m)Tc-IL-8 was intravenously injected at 400 MBq into 20 patients with various suspected localized infections. Patients were monitored for IL-8-related side effects for 4 h. Whole-body imaging was performed directly after injection and at 4 h after injection. Imaging after 24 h was performed for the first 7 patients and for subsequent patients when the results of (99m)Tc-IL-8 scintigraphy at 4 h after injection were normal or equivocal. Blood was drawn at several time points to determine the total number of leukocytes and leukocyte differentiation (all patients) and to determine pharmacokinetics (6 patients). RESULTS: (99m)Tc-IL-8 scintigraphy was performed for 20 patients (13 men and 7 women) with a mean age of 60 y (range, 21-76 y). No significant side effects were noted. Patients had suspected joint prosthesis infections (n = 9), osteomyelitis (n = 8), liver abscess (n = 1), and soft-tissue infections (n = 2). (99m)Tc-IL-8 was rapidly cleared from the blood and most other organs. In 10 of 12 patients with infections, (99m)Tc-IL-8 localized the infection at 4 h after injection. In 1 patient with vertebral osteomyelitis and in 1 patient with an infected knee prosthesis, (99m)Tc-IL-8 scintigraphy results were false-negative. In 8 patients with noninfectious disorders, no focal accumulation of (99m)Tc-IL-8 was found. CONCLUSION: Injection of (99m)Tc-IL-8 is well tolerated. (99m)Tc-IL-8 scintigraphy is a promising new tool for the detection of infections in patients as early as 4 h after injection.     

Myeloablative radioimmunotherapy in conditioning prior to haematological stem cell transplantation: closing the gap between benefit and toxicity?

High-dose radio-/chemotherapy in the context of autologous and allogeneic haematopoietic stem cell transplantation is a double-edged sword. The requirement for dose intensification is linked to an increase in toxicity to noninvolved organs. Particularly for older patients and patients with comorbidities, efficient but toxicity-reduced schemes are needed. Myeloablative radioimmunotherapy is a targeted, internal radiotherapy that uses radiolabelled monoclonal antibodies (mAb) with affinity to the bone marrow. It involves the administration of high radiation doses (up to 30 Gy) to the bone marrow and spleen but without exposing radiosensitive organs to doses higher than 1–7 Gy. Added to conventional or intensity-reduced conditioning, myeloablative radioimmunotherapy may achieve a pronounced antileukaemic effect with tolerable toxicities. A rational and individual design of the ideal nuclide–antibody combination optimizes therapy. The anti-CD33, anti-CD45 and anti-CD66 mAbs appear to be ideal tracers so far. The β-emitter ⁹⁰Y is coupled by DTPA and is the best nuclide for myeloablation. Approval trials for DTPA anti-CD66 mAb are underway in Europe, and in the near future these therapies may become applicable in practice. This review gives an overview of current myeloablative conditioning radioimmunotherapy. We discuss the selection of the optimal radioimmunoconjugate and discuss how radioimmunotherapy might be optimized in the future by individualization of therapy protocols. We also highlight the potential advantages of combination therapies.     

用核素心脏显像评价冠心病患者骨髓干细胞移植术的效果

目的用核素心脏显像评价心脏骨髓干细胞移植术的效果。方法冠心病和扩张性心肌病患者36例,在骨髓干细胞移植术前及术后随访期进行运动 静息或静息 硝酸甘油介入心肌灌注断层显像,其中15例行心室显像检查。结果术后患者缺血心肌节段及梗死心肌节段减少,分别为术前(26±04)与(36±05)个及术后(15±04)与(20±04)个。左室射血分数平均增加183%,运动低下节段数明显减少。提示术后缺血心肌血运改善,心功能部分恢复,梗死心肌区有新生心肌细胞。结论用核素心脏显像评价骨髓干细胞移植术后近期效果较有价值。     

Observations on the mechanism of 99mTc-labeled phosphate complex uptake in metabolic bone disease.

This communication describes a series of clinical and animal in vivo and in vitro investigations designed to elucidate the mechanism of 99mTc-Sn-phosphate complex concentration in metabolic bone disease. Rachitic and lathyritic animals were used as experimental models. Based on these studies it is concluded that 99mTc alters the pharmacology of the phosphate complexes, in particular pyrophosphate, which was the test agent most extensively employed, so that the usual affinity for mineral is for the greater part replaced by organic matrix binding. There is also evidence to suggest the immature collagen moiety of the organic matrix is the prime target of 99mTc-Sn-phosphate complex binding. Specifically, the aldehyde groups of the collagen molecule are suspected as being the major site of interaction.     

FDG PET and immunoscintigraphy with 99mTc-labeled antibody fragments for detection of the recurrence of colorectal carcinoma.

The aim of this study was to compare FDG PET with a new monoclonal antibody-based imaging agent that comprises an anti-carcinoembryonic antigen (CEA) monoclonal antibody Fab' fragment directly labeled with 99mTc. METHODS: Twenty-eight patients who were previously treated for colorectal carcinoma and in whom recurrence was suspected were examined with FDG PET and immunoscintigraphy. The most common indications were an elevation of serum CEA (13 patients), suggestive lesions documented by CT (9 patients), sonography (4 patients), and severe constipation (2 patients). Planar imaging and SPECT were performed 4-6 h after intravenous injection of the new imaging agent. Whole-body PET was performed 45-60 min after intravenous injection of FDG. The findings were confirmed by conventional diagnostic modalities, surgery, and histology. RESULTS: Histology confirmed local tumor recurrence in 9 of 28 patients. Clinical follow-up or CT confirmed the presence of liver metastases in 9 patients and lymph node involvement, lung metastases, and bone metastases in 2 patients each. The new agent correctly detected 8 of 9 local recurrences, whereas FDG PET was able to detect all 9 cases and in 1 case was false-positive. Liver metastases were confirmed in 9 patients by FDG PET but in only 1 patient by the new agent. Two cases with lymph node metastases and 2 cases with lung metastases were correctly identified by FDG PET, but none were detected by the new agent. Finally, bone metastases were identified in 1 patient by FDG PET but not with the new agent, whereas bone marrow infiltration (n = 1) was diagnosed by both imaging modalities. CONCLUSION: These results indicate that FDG PET and 99mTc-labeled anti-CEA Fab' are suitable for the diagnosis of local recurrence of colorectal carcinoma but that FDG PET is clearly superior in the detection of distant metastases (liver, bone, and lung) and lymph node involvement.     

Imaging acute cardiac cell death: temporal and spatial distribution of 99mTc-labeled C2A in the area at risk after myocardial ischemia and reperfusion.

The exposure of anionic phospholipids is a near-universal molecular signature for cell death. Based on our prior finding that the (99m)Tc-labeled C2A domain of synaptotagmin I accumulates intensely in the area at risk, this study quantitatively characterized the temporal and spatial distribution of the radiotracer in a rat model of myocardial ischemia and reperfusion. METHODS: Myocardial ischemia and reperfusion were induced by occlusion of the left anterior descending coronary artery in rats. The temporal uptake of the labeled fusion protein of C2A and glutathione-s-transferase (C2A-GST) in the area at risk was investigated by intravenously injecting the radiotracer at 0, 1, 3, 6, and 24 h after reperfusion, and the radioactivity uptake was quantified by gamma-counting of infarcted and ischemic noninfarcted cardiac tissues. Alternatively, the radiotracer was injected at 2 h after reperfusion, and the uptake was measured at 1, 3, 6, and 24 h after injection. In vivo planar imaging was performed on a gamma-camera using a parallel-hole collimator. The distribution of radioactivity was qualitatively examined by autoradiography. The relationship between the uptake of the radiotracer in the area at risk and the ischemic duration was examined by gamma-counting. RESULTS: Temporally, the radioactivity uptake in the area at risk maximized when the radiotracer was injected before 3 h after reperfusion. Injections at 6 and 24 h after reperfusion resulted in a 30% and 50% reduction in uptake, respectively. However, when the injection was done early (2 h after reperfusion), the tracer was retained in the area at risk with little washout for at least 24 h. Spatially prominent hot-spot uptake was seen in all cases of planar imaging. In autoradiography, the distribution of radioactivity predominantly coregistered with the infarcted regions. This distribution profile was confirmed by direct gamma-counting. In addition, the absolute radiotracer uptake in the infarcted and ischemic noninfarcted tissues, in terms of percentage injected dose per gram, was independent of the ischemic duration. CONCLUSION: (99m)Tc-C2A-GST has an uptake profile in the area at risk that is appropriate for imaging cardiac cell death in the acute phase.     

Biodistribution and radiation dosimetry of stabilized 99mTc-exametazine-labeled leukocytes in normal subjects.

Labeling leukocytes with 99mTc-exametazime is a validated technique for imaging infection and inflammation. A new radiolabeling technique has recently been described that enables leukocyte labeling with a more stable form of 99mTc-exametazime. A normal value study of stabilized 99mTc-exametazime-labeled leukocytes has been performed, including biodistribution and dosimetry estimates in normal subjects. METHODS: Ten volunteers were injected with stabilized 99mTc-exametazime-labeled autologous leukocytes to study labeled leukocyte kinetics and dosimetry in normal subjects. Serial whole-body imaging and blood sampling were performed up to 24 h after injection. Cell-labeling efficiency and in vivo viability, organ dosimetry, and clearance calculations were obtained from the blood samples and imaging data as well as urine and stool collection up to 36 h after injection. RESULTS: Cell-labeling efficiency of 87.5% +/- 5.1% was achieved, which is similar to or better than that reported with the standard preparation of 99mTc-exametazime. In vivo stability of the radiolabeled leukocytes was also similar to in vitro results with stabilized 99mTc-exametazime and better than previously reported in vivo stability for nonstabilized 99mTc-exametazime-labeled leukocytes. Organ dosimetry and radiation absorbed doses were similar with a whole-body absorbed dose of 1.3 x 10(-3) mGy/ MBq. Urinary and fecal excretion of activity was minimal, and visual assessment of the images showed little renal parenchymal activity and no bowel activity up to 2 h after injection. CONCLUSION: Cell labeling and in vivo stability appear improved compared with the leukocytes labeled with the nonstabilized preparation of 99mTc-exametazime. There are advantages in more cost-effective preparation of the stabilized 99mTc-exametazime and an extended window for clinical usage, with good visualization of abdominal structures on early images. No significant increase in specific organ and whole-body dosimetry estimates was noted compared with previous estimates using nonstabilized 99mTc-exametazime-labeled leukocytes.     

99mTc-labeled divalent and tetravalent CC49 single-chain Fv's: novel imaging agents for rapid in vivo localization of human colon carcinoma.

Radioimmunopharmaceutical agents enabling rapid high-resolution imaging, high tumor-to-background ratios, and minimal immunogenicity are being sought for cancer diagnosis and imaging. Genetic engineering techniques have allowed the design of single-chain Fv's (scFv's) of monoclonal antibodies (mAbs) recognizing tumor-associated antigens. These scFv's show good tumor targeting and biodistribution properties in vivo, indicating their potential as imaging agents when labeled with a suitable radionuclide. METHODS: Divalent (sc(Fv)(2)) and tetravalent ([sc(Fv)(2)](2)) scFv's of mAb CC49 were evaluated for radioimmunolocalization of LS-174T colon carcinoma xenografts in athymic mice. scFv's were radiolabeled with (99m)Tc by way of the bifunctional chelator succinimidyl-6-hydrazinonicotinate hydrochloride using tricine as the transchelator. The immunoreactivity and in vitro stability of the scFv's were analyzed after radiolabeling. Biodistribution and pharmacokinetic studies were performed to determine the tumor-targeting potential of the radiolabeled scFv's. Whole-mouse autoradiography illustrated the possible application of these (99m)Tc-labeled multivalent scFv's for imaging. RESULTS: The radiolabeling procedure gave > or =95% radiometal incorporation, with a specific activity of >74 MBq/mg scFv. In solid-phase radioimmunoassay, both sc(Fv)(2) and [sc(Fv)(2)](2) exhibited 75%-85% immunoreactivity, with nonspecific binding between 0.8% and 1.2%. Size-exclusion high-performance liquid chromatography showed sc(Fv)(2) as a 60-kDa protein and [sc(Fv)(2)](2) as a 120-kDa protein. Blood clearance studies showed the elimination half-life of (99m)Tc-labeled sc(Fv)(2) as 144 min and that of [sc(Fv)(2)](2) as 307 min. Whole-body clearance studies confirmed the rapid elimination of scFv's, with half-lives of 184 +/- 19 min for sc(Fv)(2) and 265 +/- 39 min for [sc(Fv)(2)](2) (P < 0.001). At 6 h after administration, the tumor localization was 7.2 +/- 0.7 percentage injected dose per gram of tumor (%ID/g) for (99m)Tc-sc(Fv)(2). (99m)Tc-[sc(Fv)(2)](2) showed a tumor uptake of 19.1 +/- 1.1 %ID/g at the same time; the amount of radioactivity in the tumors was 4-fold higher than in the spleen and kidneys and 2-fold higher than in the liver. Macroautoradiography performed at 6 and 16 h after administration clearly detected the tumor with both scFv's. CONCLUSION: (99m)Tc-labeled multivalent scFv's show good tumor-targeting characteristics and high radiolocalization indices (tumor-to-background ratio). These reagents, therefore, have the potential for use in clinical imaging studies of cancer in the field of nuclear medicine.     

A comparison of Re-188-MN-16ET-lipiodol and transcatheter arterial chemoembolization in the treatment of hepatoma: An animal study

IntroductionIn patients with unresectable HCC, transcatheter arterial chemoembolization (TACE) is a widely used treatment. Recently, as an alternative treatment modality for HCC, transcatheter arterial embolization with radioisotopes has been investigated. In this study, we compared the therapeutic efficacy of an intra-hepatic arterial injection of Re-188-MN-16ET-lipiodol and the TACE method in rats with liver tumors.MethodsTwelve male rats bearing hepatic tumors were divided into three groups to evaluate the efficacy of treatment (four in each group). Group 1 received an intra-hepatic arterial injection of 0.2 mCi of Re-188-MN-16ET-lipiodol; group 2 received epirubicin (0.5 mg/kg) and 0.1 ml of lipiodol emulsion; group 3 received 0.1 ml of normal saline and served as the control group. Tumor size was measured by liver sonography before injection, at two weeks, four weeks and eight weeks after injection. Survival time was calculated from the day of treatment to 56 days after treatment by the life-table method. The response to treatment and the survival time in each group were evaluated and compared.ResultsAll rats treated with Re-188 MN-16ET-lipiodol showed good response to the therapy. Their tumor size decreased and all rats survived over eight weeks. All rats treated with epirubicin plus lipiodol survived over 8 weeks; however, two rats (50%) showed increased tumor size in the 8th week. As for the control group (rats treated with normal saline), all rats survived less than 37 days with continuous tumor growth.ConclusionResults showed that Re-188-MN-16ET-lipiodol can be a potential therapeutic pharmaceutical for the treatment of liver tumors.     

Uptake of the 188Re(V)-DMSA complex by cervical carcinoma cells in nude mice: pharmacokinetics and dosimetry.

The uptake of the rhenium-188 (188Re(V)-DMSA) complex of dimercaptosuccinic acid by cervical carcinoma cells in nude mice was evaluated. The pharmacokinetics and dosimetry calculations in normal rats were also evaluated. The images obtained in mice did not show significant accumulation in metabolic organs and the biodistribution studies showed that 3.52 +/- 0.76% of the injected activity per gram (n = 4) was taken up by the tumor. This percentage produces a cumulated activity of 35.63 +/- 8.40 MBq h and an equivalent dose per injected activity of 260 +/- 8.91 mSv/MBq. Pharmacokinetics and dosimetry of the 1887e(V)-DMSA complex indicate that this radiopharmaceutical could be evaluated in patients with soft tissue tumors, since the risk of radiation damage to the kidney or red bone marrow could not be an obstacle for its application in therapeutic nuclear medicine.     

A prospective comparison of 99mTc-labeled polyclonal human immunoglobulin and 111In granulocytes for localization of inflammatory bowel disease.

There is a need for an easily prepared radiopharmaceutical agent for the detection of inflammation and infection. In a group of 14 patients with inflammatory bowel disease (IBD), the detection of actively involved intestinal segments by nonspecific human polyclonal immunoglobulin (IgG) labeled with 99mTc was compared with that of 111In granulocytes. To determine the specificity of 99mTc-IgG scintigraphy, 8 control patients without clinical indications of intestinal inflammation were examined. 99mTc-IgG was found in the left colon in 8 and in the right colon in 7 of the 8 controls 4 hours after the injection. At that time of scintigraphy only 4 IBD patients exhibited a more intense accumulation at the site of the intestinal segments with active disease. In contrast, in a randomized comparison with 111In granulocytes scintigraphy was positive in 11 patients with the latter technique. Moreover, fewer diseased segments were seen in the 4 patients with positive 99mTc-IgG scintigraphy (6 versus 12 with 111In granulocytes). In view of the low sensitivity and specificity, it is concluded that 99mTc-IgG is not suitable for the scintigraphic staging of IBD patients.