Jie Yuan

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.

Dopamine transporter availability in heroin-dependent subjects and controls: longitudinal changes during abstinence and the effects of Jitai tablets treatment

RationalePrevious imaging studies have indicated that the levels of the dopamine transporter (DAT) are reduced in the brains of heroin users. However, whether these changes can be reversed by abstinence and/or treatment remains unclear.ObjectivesThis study aims to investigate DAT availability in heroin users and changes in DAT availability after abstinence and treatment with the Jitai tablets, a traditional Chinese medicinal product that is approved for the treatment of opioid addiction.MethodsSingle-photon emission computed tomography (SPECT) with [99mTc] TRODAT-1 was performed on heroin-dependent patients (nu2009=u200964) and healthy controls (nu2009=u200915). The patients were randomly assigned to treatment with either placebo or the Jitai. All patients underwent SPECT imaging both at baseline and after 6xa0months of treatment. DAT availability was assessed in the caudate and putamen. Depression and anxiety were evaluated at baseline.ResultsDAT availability remained at low levels during a 6-month period in the placebo-treated group but was increased (14–17xa0%) in the Jitai-treated group. The ratio of DAT availability at month 6 to that at baseline in the Jitai-treated group was significantly higher than that in the placebo-treated group in both the bilateral caudate and putamen. DAT uptake in the striatum was significantly correlated with daily heroin dose, years of heroin use, and depression.ConclusionsThese findings suggest that chronic heroin use induces long-lasting striatal DAT reductions. DAT availability remained unchanged during a 6-month period of abstinence. Treatment with Jitai appears to be effective at increasing striatal DAT availability.

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.

Comparison of striatal dopamine transporter levels in chronic heroin‐dependent and methamphetamine‐dependent subjects

To compare the effects of heroin and methamphetamine (METH) addiction on dopamine transporters (DATs) in the same dose and duration, we assessed DAT levels in the striatum by 99mTc‐TRODAT‐1 single‐photon emission computed tomography (SPECT) brain images in people with heroin and METH dependence. We recruited 21 healthy human controls, 23 heroin‐dependent subjects and 25 METH abusers. The heroin‐ and METH‐dependent subjects exhibited negative urine toxicology after undergoing physiological detoxification. All subjects underwent SPECT brain imaging, and specific tracer uptake ratios (SURs) were assessed bilaterally in the regions of interest. A significant SUR reduction in heroin‐dependent subjects and METH‐dependent subjects compared with healthy controls was found in the left striatum, right striatum, left caudate nucleus, right caudate nucleus, left putamen and right putamen. There were no significant differences in the heroin group and METH group for the left striatum, right striatum, left caudate nucleus, right caudate nucleus, left putamen and right putamen. The scores of craving, HAMA (Hamilton Anxiety Rating Scale), in heroin abusers were lower than in the METH abusers. Our results show that people with heroin and METH dependence who are currently abstinent had lower DAT levels in the striatum than healthy controls. There were no differences in striatal DAT in heroin and METH users. These results suggest that chronic heroin and METH abuse appears to produce similar effects in striatal DAT in humans. METH users may have more serious craving and anxiety symptoms than heroin users with prolonged abstinence.

Longitudinal changes of dopamine transporters in heroin users during abstinence

RationaleChronic exposure to heroin results in decreased dopamine transporter levels. Jitai tablets, a traditional Chinese medicine, have been effective at increasing striatal dopamine transporter availability after 6xa0months of treatment. However, it remains unknown how long the heroin-induced impairment persists and whether dopamine transporter can be normalized following long-term abstinence or treatment.ObjectivesThis study was to evaluate the time course of dopamine transporter changes in heroin users undergoing long-term abstinence and treatment with Jitai tablets for 1xa0year.MethodsSingle-photon emission computed tomography using [99mTc]TRODAT-1 was performed on 64 heroin users and 20 healthy subjects to assess striatal dopamine transporter availability at baseline, 3, 6, and 12xa0months. Heroin users were randomly assigned to treatment with either placebo or Jitai tablets. Depression and anxiety scores were measured before each imaging session.ResultsCompared with healthy controls, significant reduction in dopamine transporter availability was found in heroin users at baseline in both the right (by ∼31.6xa0%) and left striatum (by ∼33.2xa0%). At 6xa0months, dopamine transporter availability was significantly higher in Jitai tablet-treated group than placebo group in the bilateral striatum (pu2009<u20090.01). At 12xa0months, dopamine transporter levels in both groups were upregulated substantially from baseline but still not recovered to normal levels in the left striatum (pu2009<u20090.05). Depression and anxiety scores significantly decreased at 3, 6, and 12xa0months (pu2009<u20090.05).ConclusionsOur results confirmed that heroin abuse induces pronounced, long-term reduction in dopamine transporter. Treatment with Jitai tablets appears to stimulate recovery.

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.