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Background/Objectives: The management of differentiated thyroid cancer (DTC) patients has undergone a major paradigm shift in past years, especially regarding the role of a careful postoperative disease assessment both in deciding for or against the use of iodine-131 therapy (i.e., patients' selection) and in selecting the correct goal of the treatment: ablative, adjuvant or therapeutic. Furthermore, diagnostic and risk-oriented uses of iodine isotopes (i.e., 123/124/131I) should always be considered during both postoperative assessment and follow-up of DTC patients to improve early staging and response assessment to initial treatments, respectively. The present review summarizes current (and real-life-related) evidence and the emerging perspectives on the therapeutic, diagnostic, and theragnostic use of radioiodine isotopes. Methods: A review of the pertinent literature was performed in PubMed, Web of Science, and Scopus without language restrictions or time limits and using one or more fitting search criteria and terms. Results: According to the literature evidence and real-life clinical practice, a risk-oriented postoperative iodine-131 therapy remains pivotal for most DTC patients and improves early disease staging through post-therapy functional imaging (i.e., theragnostic aim). Accordingly, the goal of iodine-131 therapy, the optimal strategy (empiric vs. dosimetric approach), the appropriate stimulation method [i.e., levothyroxine (L-T4) withdrawal vs. recombinant human thyrotropin (rhTSH) administration] and, finally, the suggested radioiodine activity to deliver for iodine-131 therapy (RIT) should be personalized, especially in metastatic DTC patients. Conclusions: The evidence related to the diagnostic and theragnostic use of iodine isotopes leads to a significant improvement in the postoperative risk stratification and staging of DTC patients in addition to a more accurate assessment of the response to initial treatments. In conclusion, radioiodine is really an oldie but goldie radiotracer. It has both a current fundamental role and a future perspective for the more careful management of DTC patients. [ABSTRACT FROM AUTHOR]

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123I thyroid scintigraphy can be performed with either a low energy or medium energy collimator. The high-energy photon emissions from 123I cause septal penetration with scattered photons, which deteriorate image quality. The aim of this study is to evaluate the impact of collimator choice on 123I thyroid scintigraphy in clinical practice. Methods: Forty seven patients who received thyroid planar scintigraphy with both a low energy high resolution (LEHR) collimator and a medium energy (ME) collimator were prospectively recruited using the same imaging protocol. Image quality, collimator sensitivity, and estimation of thyroid size were assessed between LEHR and ME collimators, and were compared with thyroid ultrasonography as the gold standard. Results: Images acquired with the ME collimator demonstrate less scattered background noise, improved thyroid to background contrast, and increased sensitivity in the thyroid gland compared to images acquired by the LEHR collimator. Manual measurement of the thyroid length is more accurate by using the ME collimator. Automatic estimation of the thyroid area size by using the same thyroid cutoff threshold is larger in ME collimator images than in LEHR collimator images. Conclusion:123I thyroid scintigraphy using the ME collimator generates cleaner images with less background noise and has higher collimator sensitivity for thyroid imaging compared to the LEHR collimator. Different thyroid cutoff threshold should be used to estimate the thyroid area size and volume between low and medium energy collimators. [ABSTRACT FROM AUTHOR]

To assure the credibility of commodity transfer operations in the oil and gas industry, calibrated flow meters are used to quantify the movement of fluids in the pipelines. The purpose of this paper is to validate the transient time method (TTM) to calibrate oil flow meters installed in restricted areas, using the 123I-labelled oil as a radiotracer. Traditionally, as proposed by the standard ISO 2975-7:1977 [1] for experiments in an aqueous medium, the TTM is employed by positioning two detectors at separate locations. However, in industrial plants, it is not always possible to install detectors at the distances recommended by the ISO 2975-7. The method proposed in this paper uses four scintillator detectors separated one from each other by 0.30 m and three injections containing 5.0 ml of 123I-labelled oil. The experiments were carried out in an oil flow rig with a turbulent flow profile. The results have reached an uncertainty which is lower than 1.0%. [ABSTRACT FROM AUTHOR]

Radioiodines have a long history in nuclear medicine. Herein, we discuss the production, properties and applications of these versatile iodine‐based imaging and theragnostic agents. There are 38 isotopes of iodine (I) including one stable form (127I). The most common radionuclides used in medical imaging and treatment, including Iodine‐123 (123I), Iodine‐124 (124I), Iodine‐125 (125I) and Iodine‐131 (131I), are discussed in this review. [ABSTRACT FROM AUTHOR]

A quantitative measurement, the Heart-to-Mediastinum (H/M) ratio of counts derived from a planar acquisition approximately 4 hours after injection of 123I-mIBG, is a strong predictor of outcomes in patients with stable class II-III heart failure and LVEF ≤ 35%. This study assessed the test-retest reproducibility of the H/M ratio in such patients. 47 subjects with class II-III systolic heart failure and LVEF ≤ 35% were tested at two time intervals separated by 5 to 14 days. Subjects were imaged twice on the same camera using the same radionuclide dose. Images were sent to a core analysis lab, where three nuclear technologists independently determined the H/M ratios. The primary endpoint was test-retest H/M ratio reproducibility calculated as the absolute difference in mean value determined by the three readers. Mean subject age was 65 ± 12 years, 85% were male, and mean BMI was 29 ± 6 kg/m2. Mean injected activity was 10.18 ± 0.43 mCi for first dose and 10.09 ± 0.52 mCi for the second dose. The mean and SD values for first and repeat studies were almost identical: the 95% confidence interval of the mean test-retest difference was 0.055 to 0.076. Bland-Altman plots showed no systematic effect of the H/M ratio on the magnitude of the difference between replicate measurements. Inter-reader measurements were nearly identical. There were no serious adverse events despite exposure to 123I-mIBG on 2 occasions in a short time period. The Heart-to-Mediastinum ratio of 123I-mIBG is a consistent and highly reproducible measurement in stable Class II to III heart failure patients. [ABSTRACT FROM AUTHOR]

Objectives: Although the utility of IQ-SPECT imaging using 99mTc and 201Tl myocardial perfusion SPECT has been reported, 123I-labeled myocardial SPECT has not been fully evaluated. We determined the characteristics and utility of 123I IQ-SPECT imaging compared with conventional SPECT (C-SPECT).Methods: Two myocardial phantom patterns were used to simulate normal myocardium and myocardial infarction. SPECT acquisition was performed using a hybrid dual-head SPECT/CT system equipped with a SMARTZOOM collimator for IQ-SPECT or a low-medium energy general purpose collimator for C-SPECT. Projection data were reconstructed using ordered subset expectation maximization with depth-dependent 3-dimensional resolution recovery for C-SPECT and ordered subset conjugate gradient minimizer method for IQ-SPECT. Three types of myocardial image were created; namely, no correction (NC), with attenuation correction (AC), and with both attenuation and scatter corrections (ACSC). Five observers visually scored the homogeneity of normal myocardium and defect severity of the myocardium with inferior defects by a five-point scale: homogeneity scores (5 = homogeneous to 1 = inhomogeneous) and defect scores (5 = excellent to 1 = poor). We also created a 17-segment polar map and quantitatively assessed segmental %uptake using a myocardial phantom with normal findings and defects.Results: The average visual homogeneity scores of the IQ-SPECT with NC and ACSC were significantly higher than that of C-SPECT, whereas the average visual defect scores of IQ-SPECT with AC and ACSC were significantly lower. The %uptake of all segments for IQ-SPECT with NC was significantly higher than that of C-SPECT. Furthermore, the subtraction of %uptake for C-SPECT and IQ-SPECT was the largest in inferior wall, which was approximately 10.1%, 14.7% and 14.4% for NC, AC and ACSC, respectively. The median % uptake values of the inferior wall with defect areas for C-SPECT and IQ-SPECT were 46.9% and 50.7% with NC, 59.8% and 69.2% with AC, and 54.7% and 66.5% with ACSC, respectively.Conclusion: 123I IQ-SPECT imaging significantly improved the attenuation artifact compared with C-SPECT imaging. Although the defect detectability of IQ-SPECT was inferior to that of C-SPECT, 123I IQ-SPECT images with NC and ACSC met the criteria for defect detectability. Use of 123I IQ-SPECT is suitable for routine examinations. [ABSTRACT FROM AUTHOR]

Background ― Cadmium zinc telluride (CZT) solid-state detectors have been recently introduced in the field of nuclear medicine in cardiology. The aim of the current study was to investigate the scintigraphic patterns of total uptake and the regional distribution of iodine-123 metaiodobenzylguanidine (123I-mIBG) in healthy volunteers and patients with atrial fibrillation (AF) using a gamma camera equipped CZT detectors. Material and Methods ― The total number of included subjects was 30 (15 patients with a paroxysmal form of AF and 15 healthy volunteers). Using a novel single-photon emission computed tomography (SPECT) cardiac dedicated gamma camera equipped CZT-detectors the scintigraphy was performed 15 minutes and 4 hours after intravenous administration of norepinephrine structural analogue 123I-mIBG. Thus, data from early and delayed phases were obtained. The heart-to-mediastinum ratio of 123I-mIBG uptake at 15 minutes (HMRe) and 4 hours (HMRd), as well as the washout rate (WR) and summed 123I-mIBG score (SMSe, SMSd) were measured. Results ― Patients and volunteers showed comparable results of the median ratio of 123I-mIBG uptake in the heart and mediastinum (HMR) in the early and delayed phases (p>0.05). In 14 (93%) patients with AF, 123I-mIBG uptake defects in LV myocardium were detected as compared with 8 (53%) healthy individuals (p

The possibility of labeling Cellex® with 123I was examined. Labeling was performed by oxidative iodination in the presence of Chloramine-T and Iodogen. The optimum labeling conditions were found. The target product with the radiochemical purity higher than 95% was isolated from the reaction mixture by column gel chromatography. The label distribution between constituent proteins of different molecular masses was determined by gel electrophoresis. [ABSTRACT FROM AUTHOR]

The expression of telomerase in approximately 85% of cancers and its absence in the majority of normal cells makes it an attractive target for cancer therapy. However the lag period between initiation of telomerase inhibition and growth arrest makes direct inhibition alone an insufficient method of treatment. However, telomerase inhibition has been shown to enhance cancer cell radiosensitivity. To investigate the strategy of simultaneously inhibiting telomerase while delivering targeted radionuclide therapy to cancer cells, 123 I-radiolabeled inhibitors of telomerase were synthesized and their effects on cancer cell survival studied. An 123 I-labeled analogue of the telomerase inhibitor MST-312 inhibited telomerase with an IC 50 of 1.58 μM (MST-312 IC 50 : 0.23 μM). Clonogenic assays showed a dose dependant effect of 123 I-MST-312 on cell survival in a telomerase positive cell line, MDA-MB-435. [ABSTRACT FROM AUTHOR]

Objective(s): Iodine-123 metaiodobenzylguanidine (123I-MIBG) myocardial scintigraphy has been used to evaluate cardiac sympathetic denervation in Lewy body disease (LBD), including Parkinson's disease (PD) and dementia with Lewy bodies (DLB). The heart-tomediastinum ratio (H/M) in PD and DLB is significantly lower than that in Parkinson's plus syndromes and Alzheimer's disease. Although this ratio is useful for distinguishing LBD from non-LBD, it fluctuates depending on the system performance of the gamma cameras. Therefore, a new, simple quantification method using 123I-MIBG uptake analysis is required for clinical study. The purpose of this study was to develop a new uptake index with a simple protocol to determine 123I-MIBG uptake on planar images. Methods: The 123I-MIBG input function was obtained from the input counts of the pulmonary artery (PA), which were assessed by analyzing the PA time-activity curves. The heart region of interest used for determining the H/M was used for calculating the uptake index, which was obtained by dividing the heart count by the input count. Results: Forty-eight patients underwent 123I-MIBG chest angiography and planar imaging, after clinical feature assessment and tracer injection. The H/M and 123I-MIBG uptake index were calculated and correlated with clinical features. Values for LBD were significantly lower than those for non-LBD in all analyses (P<0.001). The overlapping ranges between non-LBD and LBD were 2.15 to 2.49 in the H/M method, and 1.04 to 1.22% in the uptake index method. The diagnostic accuracy of the uptake index (area under the curve (AUC), 0.98; sensitivity, 96%; specificity, 91%; positive predictive value (PPV), 90%; negative predictive value (NPV), 93%; and accuracy, 92%) was approximately equal to that of the H/M (AUC, 0.95; sensitivity, 93%; specificity, 91%; PPV, 90%; NPV, 93%; and accuracy, 92%) for discriminating patients with LBD and non-LBD. Conclusion: A simple uptake index method was developed using 123I-MIBG planar imaging and the input counts determined by analyzing chest radioisotope angiography images of the PA. The diagnostic accuracy of the uptake index was approximately equal to that of the H/M for discriminating patients with LBD and non-LBD. [ABSTRACT FROM AUTHOR]

Correction for downscatter in I-123 SPECT can be performed by the subtraction of a secondary energy window from the main window, as in the triple-energy window method. This is potentially noise sensitive. For studies with limited amount of counts (e.g. dynamic studies), a broad subtraction window with identical width is preferred. This secondary window needs to be weighted with a factor higher than one, due to a broad backscatter peak from high-energy photons appearing at 172 keV. Spatial dependency and the numerical value of this weighting factor and the image contrast improvement of this correction were investigated in this study. Energy windows with a width of 32 keV were centered at 159 keV and 200 keV. The weighting factor was measured both with an I-123 point source and in a dopamine transporter brain SPECT study in 10 human subjects (5 healthy subjects and 5 patients) by minimizing the background outside the head. Weighting factors ranged from 1.11 to 1.13 for the point source and from 1.16 to 1.18 for human subjects. Point source measurements revealed no position dependence. After correction, the measured specific binding ratio (image contrast) increased significantly for healthy subjects, typically by more than 20%, while the background counts outside of all subjects were effectively removed. A weighting factor of 1.1-1.2 can be applied in clinical practice. This correction effectively removes downscatter and significantly improves image contrast inside the brain.

Goiter with an intrathoracic component is relatively common; however, it is less common to see extent outside the anterior or posterior mediastinum. We present a case of intrathoracic goiter of significant size and abnormal placement which is examined using both 99mTc-pertechnetate and iodine-123 single-photon emission computed tomography/computed tomography. [ABSTRACT FROM AUTHOR]

The phenyl-amino-thiazole (PAT) templates of methoxylbenzoyl-aryl-thiazole are potent agents against cancer by inhibiting tubulin polymerization in the nanomolar range. Herein, a radioiodinated PAT, [123I]-PAT 1, was prepared via a tributylstannyl precursor and [123I]iodide through electrophilic aromatic radioiodination. Radiolabelling of [123I]-PAT 1 was achieved in less than 15 min, with a radiochemical purity of over 99%. The accumulated radioactivity in tumor cellular uptake experiments suggested that [123I]-PAT could serve as a potential radioprobe for targeting tumor cells. [ABSTRACT FROM AUTHOR]

Radionuclide cardiac imaging has potential to assess underlying molecular, electrophysiologic, and pathophysiologic processes of cardiac disease. An area of current interest is cardiac autonomic innervation imaging with a radiotracer such as I- meta-iodobenzylguanidine (I- mIBG), a norepinephrine analogue. Cardiac I- mIBG uptake can be assessed by planar and SPECT techniques, involving determination of global uptake by a heart-to-mediastinal ratio, tracer washout between early and delayed images, and focal defects on tomographic images. Cardiac I- mIBG findings have consistently been shown to correlate strongly with heart failure severity, pre-disposition to cardiac arrhythmias, and poor prognosis independent of conventional clinical, laboratory, and image parameters. I- mIBG imaging promises to help monitor a patient's clinical course and response to therapy, showing potential to help select patients for an ICD and other advanced therapies better than current methods. Autonomic imaging also appears to help diagnose ischemic heart disease and identify higher risk, as well as risk-stratify patients with diabetes. Although more investigations in larger populations are needed to strengthen prior findings and influence modifications of clinical guidelines, cardiac I- mIBG imaging shows promise as an emerging technique for recognizing and following potentially life-threatening conditions, as well as improving our understanding of the pathophysiology of various diseases. [ABSTRACT FROM AUTHOR]

Aripiprazole was successfully labeled with radioactive iodine using chloramine-T via an electrophilic substitution reaction. The influence exerted on the labeling yield by reaction parameters such as concentration, pH, and time was studied to optimize the labeling conditions. The radiochemical yield was 96 ± 3%. The radioiodinated compound was separated by HPLC. In vitro studies showed that the compound was stable for up to 24 h. The brain uptake was 5.53%, which was higher than that for the commercially available Ceretec kit. The clearance from the rats occurs via the hepatobiliary and renal pathways. Predosing the rats with cold aripiprazole reduced the brain uptake to 1.9 ± 0.1% and further confirmed that the uptake of this radioiodinated compound was specific for the brain. A mechanism of the formation of electropositive iodine is discussed, and possible oxidizing species of Chloramine-T in both acidic and alkaline media are ascertained. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Tumour-associated urokinase plasminogen activator (uPA) is a critical marker of invasion and metastasis, and it is recognised as having strong prognostic relevance as well as being a therapeutic target. The specific uPA inhibitor plasminogen activator inhibitor type-2 (PAI-2, SerpinB2) specifically targets cell bound uPA and is internalised. Furthermore, preclinical studies have established the “proof-of-principle” of uPA-targeting by PAI-2-cytotoxin conjugates in human carcinoma models. However, these studies also suggest that PAI-2 is rapidly cleared via the renal system with low total dose reaching the tumour. In this study, a comparative single photon emission computed tomography (SPECT) and biodistribution (BD) analysis of different forms of PAI-2 labelled with the radioisotopes iodine-123 (123I) and technetium-99m (99mTc) was undertaken. Methods: The pharmacokinetic (PK) properties and BD of wild-type, ΔCD-loop and PEGylated ΔCD-loop PAI-2 labelled with the commonly used diagnostic SPECT radioisotopes 99mTc or 123I were compared in mouse models of human prostate carcinoma. Whole body SPECT imaging was also performed. Results: Both wild-type and the shorter but active ΔCD-loop form of PAI-2 123I-labelled indirectly via conjugation to free amine groups (termed 123I-Bn-PAI-2) exhibited low tumour uptake, rapid excretion and similar PK profiles. Preliminary studies with a short branched-chain PEGylated 123I-Bn-PAI-2 ΔCD-loop indicated an increase in blood retention time and tumour uptake. All 123I-Bn-labelled radiotracers were largely excreted through the kidneys. By comparison, both wild-type 123I-PAI-2 (labelled directly via tyrosine residues) and 99mTc-PAI-2 displayed different PK/BD patterns compared to 123I-Bn-PAI-2, suggesting greater liver based catabolism and thus slower elimination. SPECT imaging mimicked the BD results of all radiotracers. Conclusion: The different labelling methods gave distinct PAI-2 BD and tumour uptake profiles, with radioiodination resulting in the best non-tumour organ clearance profiles. Preliminary analyses with short branched-chain PEGylated 123I-Bn-PAI-2 ΔCD-loop suggest that further investigations with other PEGylation reagents are required to optimise this approach for tumour imaging. These findings impact on the use of PAI-2 for drug delivery and/or diagnostic development. [Copyright &y& Elsevier]

Abstract: This study aims to investigate the usefulness of F-18 FDG PET/CT in differentiated thyroid cancer (DTC) with elevated serum thyroglobulin (Tg) but negative iodine-123 (I-123) scan. Methods: Twenty patients with histopathologically proven DTC, negative diagnostic I-123 scan, and elevated serum Tg levels were prospectively submitted to F-18 FDG PET/CT evaluation. The histopathologic findings consisted of 19 papillary thyroid cancers, 1 follicular thyroid cancer. Results: F-18 FDG PET/CT identified lesions in 18 out of 20 patients, giving a sensitivity of 90%. Thirteen of the 18 patients revealed limited loco-regional disease. Remaining 5 patients showed distant metastases, consisting of 4 patients with lung metastases and 1 patient with bone metastasis. Two patients revealed negative F-18 FDG PET/CT findings. Conclusion: F-18 FDG PET/CT is suitable for the detection and precise localization of loco-regional recurrences and distant metastases of DTC in patients with elevated serum Tg but negative I-123 whole body scan. [Copyright &y& Elsevier]

Abstract: Introduction: A series of iodonicotinamides based on the melanin-binding iodobenzamide compound N-2-diethylaminoethyl-4-iodobenzamide was prepared and evaluated for the potential imaging and staging of disseminated metastatic melanoma. Methods: [123I]Iodonicotinamides were prepared by iododestannylation reactions using no-carrier-added iodine-123 and evaluated in vivo by biodistribution and competition studies and by single photon emission computed tomography (SPECT) imaging in black and albino nude mice bearing B16F0 murine melanotic and A375 human amelanotic melanoma tumours, respectively. Results: The iodonicotinamides displayed low-affinity binding for σ1–σ2 receptors (K i>300 nM). In biodistribution studies in mice, N-(2-(diethylamino)ethyl)-5-[123I]iodonicotinamide ([123I]1) exhibited the fastest and highest uptake of the nicotinamide series in the B16F0 tumour at 1 h (∼8% ID/g), decreasing slowly over time. No uptake was observed in the A375 tumour. Clearance from the animals by urinary excretion was more rapid for N-alkyl-nicotinamides than for piperazinyl derivatives. At 1 h postinjection, the urinary excretion was 66% ID for [123I]1, while the gastrointestinal tract amounted to 17% ID. Haloperidol was unable to reduce the uptake of [123I]1 in pigmented mice, indicating that this uptake was likely due to an interaction with melanin. SPECT imaging of [123I]1 in black mice bearing the B16F0 melanoma indicated that the radioactivity was predominately located in the tumour and eyes. No specific localisation was observed in nude mice bearing A375 amelanotic tumours. Conclusion: These findings suggest that [123I]1, which displays high tumour uptake with rapid clearance from the body, could be a promising imaging agent for the detection of melanotic tumours. [Copyright &y& Elsevier]

Purpose: The study aims to evaluate the iodinated imidazopyridine, N′, N′-diethyl-6-Chloro-(4′-[I]iodophenyl)imidazo[1,2-a]pyridine-3-acetamide ([I]-CLINDE) as a tracer for the study of peripheral benzodiazepine binding sites (PBBS). Materials and methods: In vitro studies were performed using membrane homogenates and sections from kidney, adrenals, and brain cortex of Sprague-Dawley (SD) rats and incubated with [I]-CLINDE. For in vivo studies, the rats were injected with [I]-CLINDE. In competition studies, PBBS-specific drugs PK11195 and Ro 5-4864 and the CBR specific drug Flumazenil were injected before the radiotracer. Results: In vitro binding studies in adrenal, kidney, and cortex mitochondrial membranes indicated that [I]-CLINDE binds with high affinity to PBBS, K = 12.6, 0.20, and 3.84 nM, respectively. The density of binding sites was 163, 5.3, and 0.34 pmol/mg protein, respectively. In vivo biodistribution indicated high uptake in adrenals (5.4), heart (1.5), lungs (1.5), kidney (1.5) %ID/g at 6 h p.i. In the central nervous system (CNS), the olfactory bulbs displayed the highest uptake; up to six times the activity in blood. Pre-administration of unlabeled CLINDE, PK11195 and Ro 5-4864 (1 mg/kg) reduced the uptake of [I]-CLINDE by 70-55% in olfactory bulbs. In the kidney and heart, a reduction of 60-80% ID/g was observed, while an increase was observed in the adrenals requiring 10 mg/kg for significant displacement. Flumazenil had no effect on uptake in peripheral organs and brain. Metabolite analysis indicated >90% of the radioactivity in the above tissues was intact [I]-CLINDE. Conclusion: [I]-CLINDE displays high and selective uptake for the PBBS and warrants further development as a probe for imaging PBBS using single photon emission computed tomography (SPECT). [ABSTRACT FROM AUTHOR]

Abstract: syn- and anti-1-amino-3-[2-iodoethenyl]-cyclobutane-1-carboxylic acid (syn-, anti-IVACBC 16, 17) and their analogue 1-amino-3-iodomethylene-cyclobutane-1-carboxylic acid (gem-IVACBC 18) were synthesized and radioiodoinated with [123I] in 34–43% delay-corrected yield. All these amino acids entered 9L gliosarcoma cells primarily via L-type transport in vitro with high uptake of 8–10% ID/1×106 cells. Biodistribution studies of [123I]16, 17 and 18 in rats with 9L gliosarcoma brain tumors demonstrated high tumor to brain ratios (4.7–7.3:1 at 60min post-injection). In this model, syn-, anti-, and gem-[123I]IVACBC are promising radiotracers for SPECT brain tumor imaging. [Copyright &y& Elsevier]

Abstract: An iodine-123 labeled bicyclic nucleoside analogue ([123I]-4) has been synthesized and evaluated as a potential single photon emission tomography (SPECT) reporter probe for the non-invasive imaging of expression of the varicella zoster virus thymidine kinase (VZV-tk) reporter gene. In vitro enzymatic assays revealed that the non-radioactive mono-iodo derivative 4 has good affinity for VZV-TK (IC50: 4.2μM). Biodistribution of [123I]-4 was examined in normal mice. Evaluation of [123I]-4 in HEK-293T cells showed 1.74-fold higher accumulation in VZV-TK-expressing cells compared to control cells. [Copyright &y& Elsevier]

Abstract: A series of reboxetine analogs was synthesized and evaluated for in vitro binding as racemic mixtures. The best candidate (INER) was synthesized as the optically pure (S,S) enantiomer, labeled with iodine-123 and its in vivo binding determined by SPECT imaging in baboons. The in vivo specificity, selectivity, and kinetics of [123I]INER make it a promising agent for imaging NET in vivo by noninvasive SPECT imaging. [Copyright &y& Elsevier]

Abstract: Introduction: Our objective was to compare the cell penetration and nuclear importation properties of 111In-labeled and 123I-labeled immunoconjugates (ICs) composed of 16-mer peptides (GRKKRRQRRRPPQGYG) derived from HIV-1 transactivator of transcription (tat) protein and anti-mouse IgG (mIgG) in BT-474 breast cancer (BC) cells. Methods: [111In]tat ICs were constructed by site-specific conjugation of tat peptides to NaIO4 −-oxidized carbohydrates in the Fc domain of diethylenetriaminepentaacetic-acid-modified anti-mIgG antibodies. Immunoreactivity against mIgG was assessed in a competition assay. The kinetics of the accumulation of [111In]anti-mIgG-tat IC and [123I]anti-mIgG-tat ICs in BT-474 cells and the elimination of radioactivity from cells, cytoplasm or nuclei were determined. The effects of excess tat peptides or NH4Cl (an inhibitor of endosomal acidification) on cellular uptake and nuclear importation of [111In]anti-mIgG-tat were measured. Results: [111In]anti-mIgG-tat was >97% radiochemically pure and exhibited preserved immunoreactivity with mIgG epitopes. [123I]Anti-mIgG-tat penetrated BT-474 cells more rapidly than [111In]anti-mIgG-tat ICs and achieved a 1.5-fold to a 2-fold higher uptake in cells and nuclei. Cell penetration and nuclear uptake of [111In]anti-mIgG-tat were inhibited by excess tat peptides and NH4Cl. Elimination of radioactivity from BT-474 cells and nuclei was more rapid and complete for 123I-labeled than for 111In-labeled anti-mIgG-tat ICs. Conclusion: Tat peptides derived from HIV-1 tat protein promoted the penetration and nuclear uptake of radioactivity following the incubation of 111In-labeled and 123I-labeled anti-mIgG antibodies with BT-474 human BC cells. 111In-labeled tat ICs are feasible for inserting radionuclides into cancer cells with potential for targeting intracellular and, particularly, nuclear epitopes for imaging and/or radiotherapeutic applications. [Copyright &y& Elsevier]

Abstract: A synthesis of 1-(2,4-dichlorophenyl)-5-(4-[123I]iodophenyl)-4-methyl-1H-pyrazole-3-carboxylic acid N′,N′-dimethyl-hydrazide ([123I]Me2Pyr), a new radioiodinated analogue of the high-affinity cannabinoid CB1 receptor antagonist SR141716A, is described. Labelling was achieved by radioiododestannylation of the tributylstannyl precursor with [123I]iodide in the presence of chloramine T. HPLC purification afforded the labelled product in 48% radiochemical yield. Preliminary rat brain biodistribution studies with the 125I labelled compound revealed high uptake in the substantia nigra, the globus pallidus externus and the cerebellum, which is consistent with the known distribution of CB1 receptors. [Copyright &y& Elsevier]

Abstract: In vitro binding of the iodinated imidazopyridine, N′,N′-dimethyl-6-methyl-(4′-[123I]iodophenyl)imidazo[1,2-a]pyridine-3-acetamide [123I]IZOL to benzodiazepine binding sites on brain cortex, adrenal and kidney membranes is reported. Saturation experiments showed that [123I]IZOL, bound to a single class of binding site (n H =0.99) on adrenal and kidney mitochondrial membranes with a moderate affinity (K d =30 nM). The density of binding sites was 22±6 and 1.2±0.4 pmol/mg protein on adrenal and kidney membranes, respectively. No specific binding was observed in mitochondrial–synaptosomal membranes of brain cortex. In biodistribution studies in rats, the highest uptake of [123I]IZOL was found 30 min post injection in adrenals (7.5% ID/g), followed by heart, kidney, lung (1% ID/g) and brain (0.12% ID/g), consistent with the distribution of peripheral benzodiazepine binding sites. Pre-administration of unlabelled IZOL and the specific PBBS drugs, PK 11195 and Ro 5-4864 significantly reduced the uptake of [123I]IZOL by 30% (p <0.05) in olfactory bulbs and by 51–86% (p <0.01) in kidney, lungs, heart and adrenals, while it increased by 30% to 50% (p <0.01) in the rest of the brain and the blood. Diazepam, a mixed CBR–PBBS drug, inhibited the uptake in kidney, lungs, heart, adrenals and olfactory bulbs by 32% to 44% (p <0.01) but with no effect on brain uptake and in blood concentration. Flumazenil, a central benzodiazepine drug and haloperidol (dopamine antagonist/sigma receptor drug) displayed no effect in [123I]IZOL in peripheral organs and in the brain. [123I]IZOL may deserve further development for imaging selectively peripheral benzodiazepine binding sites. [Copyright &y& Elsevier]

Abstract: Among matrix metalloproteinases (MMPs), the subfamily of gelatinases (MMP-2, MMP-9) is of particular interest due to their ability to degrade type IV collagen and other non-fibrillar collagen domains and proteins such as fibronectin and laminin. Whilst malignant cells often over-express various MMPs, the gelatinases have been most consistently detected in malignant tissues and associated with tumor growth, metastatic potential and angiogenesis. Radiosynthesis of carboxylic (1′) and hydroxamic (2′) MMPIs resulted in radiochemical yields of 70±5% () and 60±5% (), respectively. Evaluation in A549-inoculated athymic mice showed a tumor uptake of 2.0±0.7%ID/g (3h p.i.), a tumor/blood ratio of 0.5 and a tumor/muscle ratio of 4.6 at 48hp.i. for 1′. For compound 2′ a tumor uptake of 0.7±0.2%ID/g (3hp.i.), a tumor/blood ratio of 1.2 and a tumor/muscle ratio of 1.8 at 24hp.i. were observed. HPLC analysis of the blood (plasma) showed no dehalogenation or other metabolites of 1′ 2hp.i. For compound 2′, 65.4% of intact compound was found in the blood (plasma) and one polar metabolite (31%) was detected whereas in the tumor 91.8% of the accumulated activity was caused by intact compound and only 8.1% by the metabolite. Planar imaging, using a Toshiba GCA-9300A/hg SPECT camera, showed that tumor tissue could be visualized and that image quality improved by decreasing specific activity resulting in lower liver uptake, indicating some degree of saturable binding in the liver. In vivo evaluation of these radioiodinated carboxylic and hydroxamic MMP inhibitor tracers revealed that MMP inhibitors could have potential as tumor imaging agents, but that further research is necessary. [Copyright &y& Elsevier]

Purpose: No-carrier-added (nca) MIBG is primarily associated with specific uptake (i.e. uptake-1 mechanism). We evaluated the hypothesis that nca MIBG will be less influenced by changes in extra-neuronal uptake (i.e. uptake-2 mechanism) compared with carrier-added (ca) MIBG. Methods: No-carrier-added MIBG was compared with ca MIBG of two different manufacturers (ca MIBG-1 and ca MIBG-2, with a specific activity of 200 Mq/µmol and 40 MBq/µmol MIBG respectively) in rats (n = 6 per group): controls, blocking uptake-1 (desipramine) and blocking uptake-2 (phenoxybenzamine hydrochloride). Dedicated pinhole SPECT was performed 2 h after injection of the radiotracer. After SPECT, biodistribution was assessed [% injected dose per gram tissue (%ID)]. Results: No-carrier-added MIBG had the highest absolute cardiac uptake. Although a clear trend was observed, nca MIBG was not statistically significantly different from ca MIBG-1 (0.31±0.05 %ID vs 0.25±0.01 %ID, p = 0.05). Blocking uptake-1 resulted in a significant decrease in absolute cardiac uptake only for nca MIBG (0.22±0.03 %ID, p = 0.004). Blocking uptake-2 resulted in a significant reduction in ca MIBG-1 cardiac uptake (0.14±0.02 %ID, p = 0.0001), but not in the cardiac uptake of nca MIBG or MIBG-2. SPECT showed the highest relative cardiac uptake for nca MIBG. Poor contrast between myocardium and surrounding tissue hampered assessment of relative cardiac uptake on SPECT of both ca MIBG-1 and ca MIBG-2. Conclusion: No-carrier-added MIBG yields a higher myocardial uptake than ca MIBG and is associated with a higher specific as well as a lower non-neuronal uptake. We therefore conclude that for the scintigraphic assessment of the myocardial sympathetic nervous system, nca MIBG is to be preferred over ca MIBG. [ABSTRACT FROM AUTHOR]

Purpose: Our objective was to study the cellular and nuclear uptake of 123I-mouse IgG (123I-mIgG) linked to peptides [GRKKRRQRRRPPQGYGC] harbouring the membrane-translocating and nuclear import sequences of HIV-1 tat protein. Methods: Carbohydrates on mIgG were oxidized by NaIO4, then reacted with a 40-fold excess of peptides. Displacement of binding of anti-mouse IgG (Fab specific; α-mFab) to 123I-mIgG by tat-mIgG or mIgG was compared. Internalization and nuclear translocation of 123I-tat-mIgG in MDA-MB-468, MDA-MB-231 or MCF-7 breast cancer cells were measured. The immunoreactivity of imported tat-mIgG was evaluated by measuring binding of 123I-α-mFab to cell lysate and by displacement of binding of 123I-mIgG to α-mFab by cell lysate. Biodistribution and nuclear uptake of 123I-tat-mIgG, 123I-mIgG and 123I-tat were compared in mice bearing s.c. MDA-MB-468 tumours. Results: There was a 15-fold decrease in affinity of α-mFab for tat-mIgG compared with mIgG. Internalized radioactivity imported into the nucleus for 123I-tat-mIgG in MDA-MB-468,MDA-MB-231 and MCF-7 cells was 61.5±0.6%, 60.3± 3.6% and 64.7±1.0%, respectively. The binding of 123I-α-mFab to lysate from MDA-MB-468 cells importing tat mIgG was 17-fold higher than that for cells not exposed to tat-mIgG. Imported tat-mIgG competed with tat-mIgG for displacement of binding of 123I-mIgG to α-mFab. Conjugation of mIgG to tat peptides did not change tissue distribution. Nuclear localization for 123I-tat-mIgG in MDA-MB-468 tumours was 28.1±5.6%, and for liver, spleen and kidneys it was 41.7±2.7%, 13.8±0.8% and 36.9± 3.3%, respectively. Conclusion: 123I-tat-mIgG radioimunoconjugates suggest a route to the design of radiopharmaceuticals exploiting intracellular and nuclear epitopes. [ABSTRACT FROM AUTHOR]

Abstract: Melatonin demands that this hormone and its receptors be well understood. With this aim in mind, synthetic melatonin was radioiodinated with no-carrier-added (n.c.a.) sodium iodide-123 using in situ generated peracetic acid as oxidizing agent for electrophilic iodination at room temperature. The radiochemical yield was typically greater than 80% after 20min reaction time especially when relatively small amounts of activities were used (⩽10mCi). Biological evaluation was performed in normal mice. The distribution of the tracer did not reveal any specificity during the time frame studied. There was no significant retention in the whole brain. [Copyright &y& Elsevier]