Cardiac sympathetic denervation, as documented on 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy, is relatively sensitive and specific for distinguishing Parkinson\'s disease (PD) from other neurodegenerative causes of parkinsonism. The present study aims to comprehensively review the literature regarding the use of cardiac MIBG in PD. MIBG is an analog to norepinephrine. They share the same uptake, storage, and release mechanisms. An abnormal result in the cardiac MIBG uptake in individuals with parkinsonism can be an additional criterion for diagnosing PD. However, a normal result of cardiac MIBG in individuals with suspicious parkinsonian syndrome does not exclude the diagnosis of PD. The findings of cardiac MIBG studies contributed to elucidating the pathophysiology of PD. We investigated the sensitivity and specificity of cardiac MIBG scintigraphy in PD. A total of 54 studies with 3114 individuals diagnosed with PD were included. The data were described as means with a Hoehn and Yahr stage of 2.5 and early and delayed registration H/M ratios of 1.70 and 1.51, respectively. The mean cutoff for the early and delayed phases were 1.89 and 1.86. The sensitivity for the early and delayed phases was 0.81 and 0.83, respectively. The specificity for the early and delayed phases were 0.86 and 0.80, respectively.

Poly(adenosine diphosphate ribose) polymerase (PARP) has emerged as an effective therapeutic strategy against cancer that targets the DNA damage repair enzyme. PARP-targeting compounds radiolabeled with an Auger electron-emitting radionuclide can be trapped close to damaged DNA in tumor tissue, where high ionizing potential and short range lead Auger electrons to kill cancer cells through the creation of complex DNA damage, with minimal damage to surrounding normal tissue. Here, we report on [123I]CC1, an 123I-labeled PARP inhibitor for radioligand therapy of cancer. Methods: Copper-mediated 123I iododeboronation of a boronic pinacol ester precursor afforded [123I]CC1. The level and specificity of cell uptake and the therapeutic efficacy of [123I]CC1 were determined in human breast carcinoma, pancreatic adenocarcinoma, and glioblastoma cells. Tumor uptake and tumor growth inhibition of [123I]CC1 were assessed in mice bearing human cancer xenografts (MDA-MB-231, PSN1, and U87MG). Results: In vitro and in vivo studies showed selective uptake of [123I]CC1 in all models. Significantly reduced clonogenicity, a proxy for tumor growth inhibition by ionizing radiation in vivo, was observed in vitro after treatment with as little as 10 Bq [123I]CC1. Biodistribution at 1 h after intravenous administration showed PSN1 tumor xenograft uptake of 0.9 ± 0.06 percentage injected dose per gram of tissue. Intravenous administration of a relatively low amount of [123I]CC1 (3 MBq) was able to significantly inhibit PSN1 xenograft tumor growth but was less effective in xenografts that expressed less PARP. [123I]CC1 did not cause significant toxicity to normal tissues. Conclusion: Taken together, these results show the potential of [123I]CC1 as a radioligand therapy for PARP-expressing cancers.

BACKGROUND: Triple-negative breast cancer (TNBC) lacks biomarkers for targeted therapy. Auger emitters display the best therapeutic effect, if delivered directly into the nucleus proximal to DNA. The nuclear protein Poly (ADP-ribose)-Polymerase 1 (PARP1) is a suitable target against which few inhibitors (PARPi) are clinically approved for treatment of breast cancer with germline BRCA mutation (BRCAmut). In this study, a theranostic approach was investigated in a TNBC xenografted mouse model by radiolabelling a close derivative of a PARPi Olaparib (termed PARPi-01) with the Auger emitters 123/125I.
METHODS: TNBC cell line MDA-MB-231 was subcutaneously implanted in female NOD/SCID mice. At a tumour size of ~ 500mm3, [123I]PARPi-01 was administered intravenously, and SPECT/CT images were obtained at 4 h or 24 h post injection (p.i). A therapy study was performed with [125I]PARPi-01 in 4 doses (10 MBq/dose, 10 days apart). Tumour growth was monitored by CT scans longitudinally once per week. Upon reaching study endpoint, tissues were harvested and stained with TUNEL assay for detection of apoptosis induction.
RESULTS: SPECT/CT images showed rapid hepatobiliary tracer clearance at 4 h post injection (p.i.). Retention in thyroid at 24 h p.i. suggested tracer deiodination in vivo. The tumour and liver uptake were 0.2%ID/g and 2.5%ID/g, respectively. The tumour: blood ratio was 1.3. Endogenous therapy induced a significant delay in tumour growth (doubling time increased from 8.3 to 14.2 days), but no significant survival advantage. Significantly higher apoptosis ratio was observed in [125I]PARPi-01 treated tumour tissues. No radiotoxicity was detected in the liver and thyroid.
CONCLUSIONS: Considering the radio-cytotoxic effect in the tumour tissue and a delay on tumour doubling time, [125I]PARPi-01 presents a potential radiotherapeutics for treatment of TNBC. Improvements to overcome the suboptimal pharmacokinetics are necessary for its potential clinical application.

Theragnostic pairs of isotopes are used to infer radiation dosimetry for a therapeutic radiopharmaceutical from a diagnostic imaging study with the same tracer molecule labelled with an isotope better suited for the imaging task. We describe the transfer of radiation dosimetry from the diagnostic radioiodine isotope 123I, labelled for the hypoxia tracer molecule iodoazomycin arabinoside ([123I]IAZA), to isotopes 131I (therapeutic) and 124I (PET imaging). Uncertainties introduced by the dissimilar isotope half-lives are discussed in detail. Radioisotope dosimetries for [123I]IAZA were obtained previously. These data are used here to calculate residence times for 131I and 124I and their uncertainties. We distinguish two cases when extrapolating to infinity: purely physical decay (case A) and physical decay plus biological washout (case B). Organ doses were calculated using the MIRD schema with the OLIDNA/EXM code. Significant increases in some organ doses (in mSv per injected activity) were found for 131I and 124I. The most affected organs were the intestinal walls, thyroid, and urinary bladder wall. Uncertainty remained similar to 123I for case A but considerably greater for case B, especially for long biological half-lives (GI tract). Normal tissue dosimetries for IAZA must be considered carefully when substituting isotope species. A long biological half-life can significantly increase dosimetric uncertainties. These findings are relevant when considering PET imaging studies with [124I]IAZA or therapeutic administration of [131I]IAZA.

OBJECTIVE: The quantitative accuracy of Nuclear Medicine images, acquired for both planar and SPECT studies, is influenced by the isotope-collimator combination as well as image corrections incorporated in the iterative reconstruction process. These factors can be investigated and optimised using Monte Carlo simulations. This study aimed to evaluate SPECT quantification accuracy for 123I with both the low-energy high resolution (LEHR) and medium-energy (ME) collimators and 131I with the high-energy (HE) collimator.
METHODS: Simulated SPECT projection images were reconstructed using the OS-EM iterative algorithm, which was optimised for the number of updates, with appropriate corrections for scatter, attenuation and collimator detector response (CDR), including septal scatter and penetration compensation. An appropriate calibration factor (CF) was determined from four different source geometries (activity-filled: water-filled cylindrical phantom, sphere in water-filled (cold) cylindrical phantom, sphere in air and point-like source), investigated with different volume of interest (VOI) diameters. Recovery curves were constructed from recovery coefficients to correct for partial volume effects (PVEs). The quantitative method was evaluated for spheres in voxel-based digital cylindrical and patient phantoms.
RESULTS: The optimal number of OS-EM updates was 60 for all isotope-collimator combinations. The CFpoint with a VOI diameter equal to the physical size plus a 3.0-cm margin was selected, for all isotope-collimator geometries. The spheres\' quantification errors in the voxel-based digital cylindrical and patient phantoms were less than 3.2% and 5.4%, respectively, for all isotope-collimator combinations.
CONCLUSIONS: The study showed that quantification errors of less than 6.0% could be attained, for all isotope-collimator combinations, if corrections for; scatter, attenuation, CDR (including septal scatter and penetration) and PVEs are performed. 123I LEHR and 123I ME quantification accuracies compared well when appropriate corrections for septal scatter and penetration were applied. This can be useful in departments that perform 123I studies and may not have access to ME collimators.

Nuclear medicine radionuclide imaging is a quantitative imaging modality based on radioisotope-labeled tracers which emit radiation in the form of photons used for image reconstruction. Single photon emission computed tomography (SPECT) and positron emission tomography (PET) are the two noninvasive tomographic three-dimensional radionuclide imaging procedures for both clinical and preclinical settings. In this review on nuclear medicine imaging procedures in oncology, a variety of standard SPECT and PET tracers including radioiodine, 18Fluorine fluorodeoxyglucose (18F-FDG), and 68Gallium-labeled small proteins like Prostate Specific Membrane Antigen (PSMA) or somatostatin analogues and their application as targeted molecular imaging probes for improved tumor diagnosis and tumor phenotype characterization are described. Absolute and semiquantitative approaches for calculation of tracer uptake in tumors during the course of disease and during treatment allow further insight into tumor biology, and the combination of SPECT and PET with anatomical imaging procedures like computed tomography (CT) or magnetic resonance imaging (MRI) by hybrid SPECT/CT, PET/CT, and PET/MRI scanners provides both anatomical information and tumor functional characterization within one imaging session. With the recent establishment of novel molecular radiolabeled probes for specific tumor diagnosis, prognosis, and treatment monitoring, nuclear medicine has been able to establish itself as a distinct imaging modality with increased sensitivity and specificity.

A 56-y-old man underwent total thyroidectomy and bilateral central and right lateral neck dissection for papillary thyroid carcinoma with lymph nodes metastases. Before radioiodine ablation, a 123I scan established the diagnosis of primary nasolacrimal duct obstruction (dacryostenosis).

BACKGROUND: Radioactive iodine therapy is considered the treatment of choice for hyperthyroidism in cats, but the availability of this modality is limited by costs and hospitalization requirements. Administration of recombinant human thyroid stimulating hormone (rh-TSH) to humans with thyroid neoplasia or nodular goiter can increase thyroidal iodine uptake, thereby allowing the use of lower radioactive iodine doses for treatment. Veterinary studies of this subject are limited, and results are conflicting.
OBJECTIVE: To investigate the effects of rh-TSH administration on thyroidal iodine uptake in hyperthyroid cats.
METHODS: Ten client-owned hyperthyroid cats.
METHODS: In this prospective clinical study, cats were administered saline (placebo), 50 μg rh-TSH (low-dose), and 100 μg rh-TSH (high-dose) in randomized crossover design with treatments separated by 7-10 days. After each treatment, thyroid scintigraphy was performed by administering 300 μCi 123 I and assessing radionuclide uptake 8 and 24 hours later. Serum thyroid hormone concentrations were measured at each visit.
RESULTS: Thyroidal percent iodine uptakes (mean ± SD at 8 and 24 hours) in cats treated with placebo (25.2 ± 13.4%, 30.0 ± 12.8%), low-dose (24.1 ± 12.5%, 29.4 ± 13.7%), and high-dose rh-TSH (24.2 ± 16.3%, 30.8 ± 15.3%) were not different (P = .76). Independent of rh-TSH administration, percent iodine uptakes were positively correlated with serum thyroid hormone concentrations.
CONCLUSIONS: One-time administration of rh-TSH, even at high doses, would not be expected to lower radioactive iodine doses needed for treatment of hyperthyroidism in cats. Investigations of alternate strategies to increase thyroidal uptake of radioactive iodine are warranted.

Low-energy characteristic x-rays emitted by 111In and 123I sources are easily absorbed by the containers of the sources, affecting radioactivity measurements using a dose calibrator. We examined the effects of different containers on the estimated activities. The radioactivities of 111In, 123I, 201Tl, and 99mTc were measured in containers frequently employed in clinical practice in Japan. The 111In measurements were performed in the vials A and B of the 111In-pentetreotide preparation kit and in the plastic syringe. The activities of 123I-metaiodobenzylguanidine and 201Tl chloride were measured in the prefilled glass syringes and plastic syringes. The milking vial, vial A, vial B, and plastic syringe were used to assay 99mTc. For 111In and 123I, measurements were performed with and without a copper filter. The filter was inserted into the well of the dose calibrator to absorb low-energy x-rays. The relative estimate was defined as the ratio of the activity estimated with the dose calibrator to the standard activity. The estimated activities varied greatly depending on the container when 111In and 123I sources were assayed without the copper filter. The relative estimates of 111In were 0.908, 1.072, and 1.373 in the vial A, vial B, and plastic syringe, respectively. The relative estimates of 123I were 1.052 and 1.352 in the glass syringe and plastic syringe, respectively. Use of the copper filter eliminated the container-dependence in 111In and 123I measurements. Container-dependence was demonstrated in neither 201Tl nor 99mTc measurements. The activities of 111In and 123I estimated with a dose calibrator differ greatly among the containers. Accurate estimation may be attained using the container-specific correction factor or using the copper filter.

BACKGROUND: [123I]FP-CIT is a well-established radiotracer for the diagnosis of dopaminergic degenerative disorders. The European Normal Control Database of DaTSCAN (ENC-DAT) of healthy controls has provided age and gender-specific reference values for the [123I]FP-CIT specific binding ratio (SBR) under optimised protocols for image acquisition and processing. Simpler reconstruction methods, however, are in use in many hospitals, often without implementation of attenuation and scatter corrections. This study investigates the impact on the reference values of simpler approaches using two quantifications methods, BRASS and Southampton, and explores the performance of the striatal phantom calibration in their harmonisation.
RESULTS: BRASS and Southampton databases comprising 123 ENC-DAT subjects, from gamma cameras with parallel collimators, were reconstructed using filtered back projection (FBP) and iterative reconstruction OSEM without corrections (IRNC) and compared against the recommended OSEM with corrections for attenuation and scatter and septal penetration (ACSC), before and after applying phantom calibration. Differences between databases were quantified using the percentage difference of their SBR in the dopamine transporter-rich striatum, with their significance determined by the paired t test with Bonferroni correction. Attenuation and scatter losses, measured from the percentage difference between IRNC and ACSC databases, were of the order of 47% for both BRASS and Southampton quantifications. Phantom corrections were able to recover most of these losses, but the SBRs remained significantly lower than the \"true\" values (p < 0.001). Calibration provided, in fact, \"first order\" camera-dependent corrections, but could not include \"second order\" subject-dependent effects, such as septal penetration from extra-cranial activity. As for the ACSC databases, phantom calibration was instrumental in compensating for partial volume losses in BRASS (~67%, p < 0.001), while for the Southampton method, inherently free from them, it brought no significant changes and solely corrected for residual inter-camera variability (-0.2%, p = 0.44).
CONCLUSIONS: The ENC-DAT reference values are significantly dependent on the reconstruction and quantification methods and phantom calibration, while reducing the major part of their differences, is unable to fully harmonize them. Clinical use of any normal database, therefore, requires consistency with the processing methodology. Caution must be exercised when comparing data from different centres, recognising that the SBR may represent an \"index\" rather than a \"true\" value.