A.G.M. Janssen

[123I]FP-CIT SPECT shows a pronounced decline of striatal dopamine transporter labelling in early and advanced Parkinson's disease.

OBJECTIVES: The main neuropathological feature in Parkinsons disease is a severe degeneration of the dopaminergic neurons in the substantia nigra resulting in a loss of dopamine (DA) transporters in the striatum. [123I]beta-CIT single photon emission computed tomography (SPECT) studies have demonstrated this loss of striatal DA transporter content in Parkinsons disease in vivo. However, studies with this radioligand also showed that an adequate imaging of the striatal DA transporter content could only be performed on the day after the injection of radioligand, which is not convenient for outpatient evaluations. Recently, a new radioligand [123I]FP-CIT, with faster kinetics than beta-CIT, became available for imaging of the DA transporter with SPECT, and the applicability of this ligand was tested in patients with early and advanced Parkinsons disease, using a one day protocol. METHODS: [123I]FP-CIT SPECT was performed in six patients with early and 12 patients with advanced Parkinsons disease, and in six age matched healthy volunteers. RESULTS: Compared with an age matched control group striatal [123I]FP-CIT uptake in patients with Parkinsons disease was decreased, and this result was measurable three hours after injection of the radioligand. In the Parkinsons disease group the uptake in the putamen was reduced more than in the caudate nucleus. The contralateral striatal uptake of [123I]FP-CIT was significantly lower than the ipsilateral striatal uptake in the Parkinsons disease group. Specific to non-specific striatal uptake ratios correlated with the Hoehn and Yahr stage. A subgroup of patients with early Parkinsons disease also showed significantly lower uptake in the putamen and lower putamen:caudate ratios than controls. CONCLUSION: [123I]FP-CIT SPECT allows a significant discrimination between patients with Parkinsons disease and age matched controls with a one day protocol, which will be to great advantage in outpatient evaluations.

[123I]FP-CIT binds to the dopamine transporter as assessed by biodistribution studies in rats and SPECT studies in MPTP-lesioned monkeys

[123I]FP‐CIT (N‐ω‐fluoropropyl‐2β‐carbomethoxy‐3β‐{4‐iodophenyl}tropane), a radioiodinated cocaine analogue, was evaluated as an agent for the in vivo labeling of dopamine (DA) transporters by biodistribution studies in rats and by single photon emission computed tomography (SPECT) studies in unilateral 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)–lesioned monkeys. In rats, intravenous injection of [123I]FP‐CIT resulted in high accumulation of radioactivity in the striatum. Less pronounced uptake was seen in brain areas with high densities of serotonergic uptake sites. While striatal uptake of radioactivity after injection of [123I]FP‐CIT was displaced significantly by GBR12,909 but not by fluvoxamine, the opposite was observed in brain areas known to be rich of serotonin transporters. Monkeys which were unilaterally treated with neurotoxic doses of MPTP showed severe loss of striatal [123I]FP‐CIT uptake at the side of treatment. The results of this study indicate that [123I]FP‐CIT, although not being a selective radioligand, binds specifically to the striatal DA transporter in vivo and thus suggest that [123I]FP‐CIT promises to be a suitable radioligand for SPECT imaging of DA transporters in humans. Synapse 27:183–190, 1997.

[123I]FP-CIT SPECT is a useful method to monitor the rate of dopaminergic degeneration in early-stage Parkinson's disease

Summary. We investigated the applicability [123I]FP-CIT SPECT for the assessment of the rate of dopaminergic degeneration in PD. Twenty early-stage PD patients (age range 43–73 yr; mean age 55.4) were examined twice, a mean of 12 months apart. The mean annual change in the ratio of specific to nonspecific [123I]FP-CIT binding to the striatum was used as the outcome measure. The mean annual decrease in striatal [123I]FP-CIT binding ratios was found to be about 8% (of the baseline mean). In order to demonstrate a significant effect (p < 0.05) of putative neuroprotective agent with 0.80 power and 50% of predicted protection within 2 years, 36 patients are required in each group, when the effects are measured by means of changes in [123I]FP-CIT binding ratios in whole striatum. Our findings indicate that [123I]FP-CIT SPECT seems to be a useful tool to investigate the progression of dopaminergic degeneration in PD and may provide an objective method of measuring the effectiveness of neuroprotective therapies.

Evaluation of [123I]β-CIT binding with SPECT in controls, early and late Parkinson's disease

The main neuropathological feature in Parkinsons disease (PD) is a severe degeneration of the dopaminergic neurons in the substantia nigra resulting in a loss of dopamine in the striatum. Recently, a new radioligand (beta-CIT) for single photon emission computed tomography (SPECT) became available for in vivo imaging of the dopamine transporter on nerve endings of dopaminergic neurons in the striatum. The present results demonstrate that [123I]-beta-CIT SPECT allows a discrimination between early and late PD patients. In our opinion, these preliminary data suggest that [123I]-beta-CIT SPECT should be used from now on in longitudinal studies (such as the DATATOP study) in which the effects of (putative) neuroprotective interventions in PD are monitored.

Imaging of estrogen receptors in primary and metastatic breast cancer patients with iodine-123-labeled Z-MIVE

PURPOSE To evaluate the feasibility of noninvasive imaging of estrogen receptors (ERs) in primary and metastatic breast cancer with the iodine-123-labeled ER-specific ligand cis-11beta-methoxy-17alpha-iodovinylestradiol-17beta (Z-[123I]MIVE) using conventional nuclear medicine techniques. PATIENTS AND METHODS Z-[123I]MIVE planar scintigraphy and single-photon emission computed tomography (SPECT) were performed in 12 patients with proven primary breast cancer and 13 patients with proven or from other imaging modalities evident bone, liver, lung, pleura and/or lymph node metastases. The results were compared with those of ER immunohistochemistry (IHC). Blocking studies with the antiestrogen tamoxifen were performed to test whether Z-[123I]MIVE tumor uptake was ER-mediated. RESULTS Planar imaging showed uptake in 11 of 12 primary carcinomas. ER IHC performed for nine of these was positive. For the planar scintigraphy-negative patient, SPECT was faintly positive, but ER IHC negative (agreement, 90%). In nine of 13 metastatic patients, planar scintigraphy was positive. The agreement between the results of ER IHC on the original primary tumor and of Z-[123I]MIVE scintigraphy was 82%. Specificity of tumor Z-[123I]MIVE uptake was established by complete blockade of uptake by tamoxifen, except in two patients who showed progressive disease. Z-[123I]MIVE scintigraphy also enabled discriminating metastases from confounding nonmalignant abnormalities of the bone scan. CONCLUSION Z-[123I]MIVE scintigraphy shows high sensitivity and specificity for the detection of ER-positive breast cancer. This may have impact on diagnostic possibilities and therapeutic management. Since ER imaging shows the functional status, addressing known intratumoral and intertumoral ER heterogeneity, it may improve the characterization of disease and the selection of patients who may benefit from hormonal therapy.

Dosimetry of iodine-123 iodobenzamide in healthy volunteers

The distribution of the dopamine D2-receptor specific ligand iodine-123 (S)-(−)-2-hydroxy-3-iodo-6-methoxy-N[(1-ethyl-2-pyrrolidinyl)methyl]-benzamide (1231-IBZM) was investigated in human adults from whole-body scans, blood samples and urine collected up to 48 h after injection. Results from the present study performed in six healthy volunteers were combined with those of five volunteers from a previous study. Using the brain, liver, lungs and spleen as source organs, the MIRD method was applied to calculate the absorbed radiation dose of the radioligand in various organs. The thyroid (despite blockage), gall-bladder wall, large intestinal walls and spleen received the highest absorbed doses. The average effective dose equivalent of 123I-IBZM for adults was estimated to be 0.034 mSv/MBq. The absorbed dose to the thyroid may be a limiting factor for 1231-IBZM studies in children.