Xingdang Liu

Efficacy and safety of 177Lu-EDTMP in bone metastatic pain palliation in breast cancer and hormone refractory prostate cancer: a phase II study.

Purpose 177Lu-labeled ethylenediamine-N,N,N′,N′-tetrakis methylene phosphonic acid (177Lu-EDTMP), was used to palliate metastatic bone pain as a new bone-seeking radiopharmaceutical. In this phase II study, we assessed the efficacy and safety of 177Lu-EDTMP for bone pain palliation in patients with breast cancer and hormone refractory prostate cancer with bone metastases. Methods Sixteen patients were enrolled in the trial and were subsequently divided into 2 groups, the low-dose group (1295 MBq) and the high dose group (2590 MBq) to determine differences in toxicities and response rates. Pain scores, Karnofsky indices, mobility scores, and requirement of analgesic administration were assessed at 0, 2, 4, 6, 8, and 12 weeks after injection of 177Lu-EDTMP. Toxicity was assessed by analyzing hemoglobin, leukocyte, and platelet counts. Results An obvious reduction in the mean pain score was observed at 2 to 6 weeks after the administration of 177Lu-EDTMP. The rate of complete responses in bone pain palliation was 55% in group 1 and 80% in group 2 at 6 weeks after treatment. Of the 5 patients who required additional analgesics, all were able to reduce or completely stop taking these medications by 4 weeks after therapy. Mean (SD) Karnofsky indices of 58.18 (9.82) (range, 50–70) and 56.00 (8.94) (range, 50–70) at baseline increased to 82.73 (9.05) (range, 60–90) at 6 weeks after 177Lu-EDTMP treatment in group 1 and 85.00 (5.77) (range, 80–90) at 8 weeks after injection in group 2, respectively. Mobility scores decreased from 2.91 (1.04) (range, 1–4) and 2.80 (0.84) (range, 2–4) at baseline to 1.00 (0.67) (range, 0–2) and 0.50 (0.58) (range, 0–1) at 8 weeks after administration of 177Lu-EDTMP in groups 1 and 2, respectively, primarily owing to improved mobility. In group 1, 1 patient experienced grade III toxicity in both hemoglobin and platelet counts. No grade IV toxicities were observed. In group 2, there were no grade III or IV toxicities found in hemoglobin, platelets, or leukocytes counts. Moreover, no clinically significant adverse effects were observed, and no significant differences in either efficacy or safety were detected between the 2 dose levels. Conclusions This study indicated that 177Lu-EDTMP was an effective and safe treatment for palliation of metastatic bone pain in patients with prostate or breast cancer. A dose of 1295 MBq (35 mCi) was sufficient for bone pain palliation therapy, and doses as high as 2590 MBq (70 mCi) were well tolerated.

99mTc‐TRODAT‐1 SPECT study in early Parkinson's disease and essential tremor

Objective –  The clinical differentiation between early Parkinsons disease (PD) and essential tremor (ET) could be difficult, therefore, the aim of this study was to investigate 99mTc‐TRODAT‐1 SPECT as an applicable tool in this field.

Dopamine transporter dysfunction in Han Chinese people with chronic methamphetamine dependence after a short-term abstinence.

Single-photon emission-computed tomography (SPECT) after the administration of (99m)Tc-TRODAT-1 was performed on healthy subjects and subjects with methamphetamine (METH)dependence at time 1 (T1) after 24-48 h of abstinence, time 2 (T2) after 2 weeks of abstinence, and time 3 (T3) after 4 weeks of abstinence. In contrast to values in controls, the values of the striatal DAT specific uptake ratios (SURs) in subjects with METH dependence were significantly lower at T1 (n=25), T2 (n=9), and T3 (n=8); a mild increase in SURs was observed at T2 and T3, but values were still significantly lower than those in controls. In subjects with METH dependence, there was a trend for a negative correlation of striatal DAT SURs and craving for METH at T1. METH craving, anxiety and depression scores significantly decreased from T1 to T2 to T3. We conclude that Han Chinese people with METH dependence experience significant striatal DAT dysfunction, and that these changes may be mildly reversible after 4 weeks of abstinence, but that DAT levels still remain significantly lower than those in healthy subjects. The mild recovery of striatal DAT may parallel improvements in craving, anxiety and depression.

Timing and optimized acquisition parameters for the whole-body imaging of 177Lu-EDTMP toward performing bone pain palliation treatment

ObjectivesLutetium-177-labeled ethylenediamine-N,N,N′,N′-tetrakis (methylene phosphonic acid) (177Lu-EDTMP), a beta-emitting bone-seeking therapeutic radiopharmaceutical being assessed as an agent for palliation of bone pain, can emit suitable gamma-photons for scintigraphy. This investigation sought to characterize its optimal conditions for whole-body gamma camera imaging in patients. Materials and methodsEleven patients with bone metastases underwent whole-body bone scanning using both 99mTc-methyl-diphosphonate (99mTc-MDP) and 177Lu-EDTMP (29.4±12.5 MBq/kg BW) utilizing a dual-head camera. For lutetium-177 imaging, two types of collimators, low-energy high-resolution (LEHR) and medium-energy general-purpose (MEGP), and two different peak energies of 113 and 208 keV were used. ResultsThe femur-to-muscle uptake ratio (F/M) of 99mTc-MDP was 2.69±1.06. For 177Lu-EDTMP, the significantly highest F/Ms were found at 24 h (12.59±5.73) and 48 h (12.54±5.23) by applying MEGP collimators and collecting the 208 keV photons. In all the combinations of collimator and peak energy, the F/Ms at 24 and 48 h are significantly higher than those at 1 h, except the combination of LEHR collimator and 208 keV peak energy. Lesion-to-normal bone uptake ratios of the 99mTc-MDP bone scan and images at the 24 and the 48-h phases of 177Lu-EDTMP were analyzed. MEGP and 208 keV had significantly higher values in lesion-to-normal bone uptake ratios. The combination of LEHR and 208 keV provided the poorest images. Conclusion177Lu-EDTMP can provide fine whole-body images with the best results when applying medium-energy collimation and collecting the 208 keV energy photons and alternatively by collecting both 208 and 113 keV photons for higher count statistics. The most appropriate time point for imaging is around 24 h after injection.

Study on retinal dopamine transporter in form deprivation myopia using the radiopharmaceutical tracer 99mTc-TRODAT-1.

PurposeTo investigate the distributions and changes in dopamine transporters (DATs) using 99mTc-TRODAT-1 ([99mTc-(2((2-(((3-(4-chlorophenyl)-8-methyl-8-azabicyclo(3,2,1)-oct-2-yl)-methyl)(2-mercaptoethyl)amino)ethyl)amino)ethane-thiolato(3-)-N2,N2′,S2,S2)oxo-(1R-(exo-exo)))]) in form deprivation myopia retina. MethodsPigmented guinea pigs aged 3 weeks were randomly assigned into two groups: form-deprivation myopia and normal control group. The test group wore a translucent goggle covering randomly for 4 weeks, and both groups underwent biometric measurement before and after the experiment. Both Micro-single-photon emission computed tomography (SPECT) imaging and ex-vivo autoradiography were performed with the injection of 99mTc-TRODAT-1 on the 4th week for all the guinea pigs. ResultsThe retinas were clearly resolved with 99mTc-TRODAT-1 in both Micro-SPECT imaging and ex-vivo autoradiography. In Micro-SPECT imaging, the ratio of 99mTc-TRODAT-1 uptake in the myopic retinas (11.55±2.80) was 3.64±1.40 lower than that in the normal control eyes (15.20±1.98, P=0.026, F=2.94, t=2.605), and 2.35±1.05 lower than that in the fellow eyes (13.90±2.04, P=0.003, t=5.476). In ex-vivo autoradiography, the ratio of 99mTc-TRODAT-1 uptake in the myopic retina (95.52±12.04) was 18.54±5.86 lower than in the normal control eyes (114.06±7.81, P=0.01, F=0.331, t=3.164), and was 16.95±5.78 lower than in the fellow eyes (112.47±15.67, P=0.001, t=7.179). Conclusion99mTc-TRODAT-1 can be used to trace the distributions and changes in DAT in the retina. DATs in the myopic retinas were lower than that in the fellow and normal control eyes. Radionuclide tracing may provide a new approach in vivo for further studies on the dopamine system in myopia.

Availability of dopamine transporters in heroin-dependent subjects: A 18F-FECNT PET imaging study

This study was to reconfirm the reduced dopamine transporter (DAT) availability in heroin-dependent subjects and validate the use of 2β-carbomethoxy-3β-(4-chlorophenyl)-8-(2-fluoroethyl)-nortropane (18F-FECNT) as a PET radiotracer to assess the changes of striatal DAT in drug addicted subjects. Herein, we assessed DAT standardized uptake values (SUV) of 18F-FECNT in the striatum and cerebellum of 20 heroin-dependent subjects and 10 healthy controls and analyzed the correlation between DAT availability and heroin withdrawal symptom scores and anxiety/depression rating scales in heroin-dependent subjects, as well as the relationship between the withdrawal symptoms scores and age. The striatal DAT availability in heroin-dependent subjects was significantly lower (by ~15.7-17.6%) than that in healthy controls. Age was positively related to heroin withdrawal symptom scores. The withdrawal symptom scores in older patients (Age: 49.5±2.5) were significantly higher (by ~20%) than those in younger patients (Age: 30.9±4.8). These results confirm that chronic heroin use induces striatal DAT reduction, suggesting that 18F-FECNT could be used as an alternative PET imaging radioligand for in vivo imaging of DAT in drug addicted subjects. Moreover, older patients might suffer more severe withdrawal symptoms than younger patients, suggesting that older patients with heroin withdrawal could be given more medication.

Protective and restorative effects of the traditional Chinese medicine Jitai tablet against methamphetamine-induced dopaminergic neurotoxicity

BackgroundMethamphetamine (METH) is a psychostimulant with high abuse liability that affects the monoamine neurotransmitter systems, particularly the dopamine system. Currently there are no effective medications for the treatment of METH abuse to restore METH-induced dopaminergic dysfunction. The Jitai tablet (JTT), a commercial traditional Chinese medicinal preparation, has been shown to modulate the dopaminergic function both in heroin addicts and in morphine-dependent rats. The purpose of this study was to investigate, in a rodent model, whether JTT can protect against METH-induced neurotoxicity, and/or restore METH-damaged dopaminergic function.MethodsImmunohistochemical staining and/or autoradiography staining were used to detect tyrosine hydroxylase (TH) expression in the substantia nigra, and to examine the levels of dopamine transporter (DAT), dopamine D2 receptor (D2R) and TH levels in the striatum. Using a stereotyped behavior rating scale, we evaluated the inhibitory effect of JTT on METH-induced behavioral sensitization.ResultsRepeated METH administration induced obvious stereotyped behavior and neurotoxicity on the dopaminergic system. Pre-treatment with JTT significantly attenuated METH-induced stereotyped responses, and interdicted METH-induced changes in the levels of DAT, D2R and TH expression. Treatment with JTT after METH administration restored DAT, D2R and TH expression to normal levels.ConclusionsOur results indicated that JTT protects against METH-induced neurotoxicity and restores the dopaminergic function, and thus might be a potential treatment for the dopaminergic deficits associated with METH abuse.

Feasibility of 99mTc-TRODAT-1 Micro-SPECT imaging of dopamine transporter in animal retinas

In this paper, (99m)Tc-TRODAT-1 Micro-SPECT (single-photon emission computed tomography) was used for imaging dopamine transporter (DAT) in retinas and to investigate the changes of DAT in retinas of pigs with form deprivation myopia. Pigmented guinea pigs aged 3 weeks were devided into form deprivation myopia (FDM) group (n=6) and normal control group (n=6). The test group wore translucent goggles randomly for 4 weeks, and both groups underwent biometric measurement (refraction and axial length) before and after the experiment. Micro-SPECT retinas imaging was performed at the 4(th) week after injection of (99m)Tc-TRODAT-1. The retinas were clearly resolved in the images. The ratio of (99m)Tc-TRODAT-1 uptake in the myopic retinas (11.55 +/- 2.80) was 3.64 +/- 1.40 lower than that in the control eye (15.20 +/- 1.98), and 2.35 +/- 1.05 lower than that in the fellow eyes (13.90 +/- 2.04). The results showed that (99m)Tc-TRODAT-1 Micro-SPECT eye imaging can be used to trace the distribution and changes of DAT in retina, and DAT in the myopic retinas were lower than that in the normal control eyes and fellow eyes. Micro-SPECT may provide a new approach for further studies on the role of dopamine system in the experimental myopia.

Comparable investigation in dopamine transporters with 99mTc-TRODAT-1 and 131I-FP-CIT SPECT in Parkinson's disease patients

Abstract Dopamine transporter (DAT) mediates the regulation of dopaminergic function. Two agents of TRODAT-1 and FP-CIT were observed in evaluating DAT change of Parkinsons disease (PD). The relationship between them was also evaluated. The results suggested that 99m Tc-TRODAT-1 SPECT and 131 I-FP-CIT SPECT may serve as sensitive and objective in vivo markers to reflect the severity of PD. The 99c Tc-TRODAT-1 image is more accurate and clearer compared with 131 I-FP-CIT.