Clinical implications of primary "occult" vesicoureteral reflux in male children.

OBJECTIVES: To compare characteristics and outcomes of vesicoureteral reflux (VUR) detected solely on isotopic cystography (IC) ("occult" VUR) with voiding cystourethrography (VCUG)-detected VUR. MATERIALS AND METHODS: Between 2015 and 2020, we retrospectively enrolled all male children first undergoing VCUG and, if negative, IC in the same session. Kidney injury (KI) was defined by abnormal estimated glomerular filtration rate and/or blood pressure and/or proteinuria. RESULTS: We enrolled 421 males with a median age of 3 months and a follow-up of 5.3 years. None exhibited KI initially, but 10% of those with VUR developed KI during follow-up. Two hundred and twenty-two patients (52.7%) did not show VUR, 152 (36.1%) had VCUG-diagnosed VUR, and 47 (11.2%) had occult VUR. Therefore, 47/199 patients (23.6%) with VUR had occult VUR. Among these, 34/47 (72.3%) had dilated VUR, and 22/47 (46.8%) exhibited split renal function < 45% and/or scar (scintigraphic damage). Compared to patients with occult VUR, those with VCUG-diagnosed VUR showed a similar prevalence of febrile urinary tract infection (fUTI) before and after VUR diagnostics and KI at the last follow-up but a higher prevalence of dilated VUR, of scintigraphic damage, and underwent surgery more frequently. At multiple logistic regression analysis, patients with VCUG-diagnosed VUR presented an increased risk of fUTI either before or after VUR diagnosis and of KI, while patients with occult VUR presented an increased risk of fUTI before (and among patients with dilated VUR also after) VUR diagnosis and of KI. CONCLUSION: Occult VUR affects 23.6% of male children with VUR with a non-negligible risk of VUR-associated KI and fUTI. IC could select, among males with recurrent fUTIs and negative VCUG, those requiring surgery for a possible dilated occult VUR. CLINICAL RELEVANCE STATEMENT: Vesicoureteral reflux may be overlooked in 25% of boys during VCUG, yet they are at risk of fUTIs and KI. In case of recurrent infections post-negative cystourethrography, IC could detect occult reflux, guiding surgical intervention.

Effect of variable left ventricular ejection fraction assessed by equilibrium radionuclide angiocardiography using different software packages on the diagnosis of cardiotoxicity in patients with cancer.

BACKGROUND: The equilibrium radionuclide angiocardiography (ERNA) scan is an established imaging modality for assessing left ventricular ejection fraction (LVEF) in oncology patients. This study aimed to explore the interchangeability of two commercially available software packages (MIM and JS) for LVEF measurement for a cancer-therapy-related cardiac dysfunction (CTRCD) diagnosis. METHODS: This is a single-center retrospective study among 322 patients who underwent ERNA scans. A total of 582 scans were re-processed using MIM and JS for cross-sectional and longitudinal LVEF measurements. RESULTS: The median LVEF for MIM and JS were 56% and 66%, respectively (P < 0.001). LVEF processed by JS was 9.91% higher than by MIM. In 87 patients with longitudinal ERNA scans, serial studies processed by MIM were classified as having CTRCD in a higher proportion than serial studies processed by JS (26.4% vs 11.4%, P = 0.020). There were no significant differences in intra- or inter-observer LVEF measurement variability (R = 0.99, P < 0.001). CONCLUSIONS: Software packages for processing ERNA studies are not interchangeable; thus, reports of ERNA studies should include details on the post-processing software. Serial ERNA studies should be processed on the same software when feasible to avoid discrepancies in the diagnosis and management of CTRCD.

Gastroparesis might not be uncommon in patients with diabetes mellitus in a real-world clinical setting: a cohort study.

BACKGROUND: This study investigated the frequency of diabetic gastroparesis and associated risk factors in a real-world clinical setting. METHODS: This retrospective cross-sectional study included patients who underwent assessments of solid gastric emptying time (GET) by technetium-99 m scintigraphy between May 2019 and December 2020. We categorized patients into three groups according to gastric retention of technetium-99 m: rapid (< 65% at 1 h or < 20% at 2 h), normal (≤60% at 2 h and/or ≤ 10% at 4 h), and delayed (> 60% at 2 h and/or > 10% at 4 h). RESULTS: Patients with diabetes mellitus (DM) were more likely to show abnormal GET than those without DM (119 [70.8%] vs. 16 [44.4%]). The mean glycated A1c was 10.3% in DM patients. DM patients with normal GET were significantly younger (57.2 years, P = 0.044) than those with delayed (65.0 years) or rapid GET (60.2 years). Fasting glucose levels were the lowest in the normal GET group and the highest in the rapid GET group (delayed: 176.3 mg/dL, normal: 151.2 mg/dL, rapid: 181.0 mg/dL, P = 0.030). However, glycated A1c was not significantly different among the delayed, normal, and rapid GET groups in patients with DM. Patients with delayed and rapid GET showed a higher frequency of retinopathy (6.0 vs. 15.5%, P = 0.001) and peripheral neuropathy (11.3 vs. 24.4%, P = 0.001) than those with normal GET. In the multinomial logistic regression analysis, retinopathy demonstrated a positive association with delayed GET, while nephropathy showed a significant negative correlation. CONCLUSION: DM gastroparesis in the clinical setting was not uncommon. Abnormal GET, including delayed and rapid GET, was associated with DM retinopathy or peripheral neuropathy.

Randomized, crossover trial: comparing the effects of standardized egg-white meal and Vital® on global gastric emptying parameters and intragastric meal distribution in healthy Asian participants.

BACKGROUND AND AIM: Measurements of gastric emptying and accommodation for alternative test-meal protocol during gastric emptying scintigraphy (GES), such as high-calorie nutrient drinks, are not fully established. We aimed to compare the effects of standardized egg-white meal (EWM) versus high-calorie nutrient drink (Vital®; Abbott Laboratories) on global GES parameters and intragastric meal distribution at immediate scan (IMD0h). METHODS: Of 84 screened participants, 60 asymptomatic healthy Asian population (38 females; 24.0 ± 1.5 years; 23.8 ± 2.6 kg/m2) were recruited in this 2 × 2 (AB/BA) crossover trial. Participants were randomized to a 4-h GES with 99mTc-radiolabeled EWM (~255.8 kcal), followed by a 200 mL Vital® (300 kcal), or vice versa, separated by a 2-week washout period. Global meal retention (GMR), power-exponential model emptying parameters (half-emptying [T1/2], lag phases [Tlag2%, Tlag5%, Tlag10%]), and IMD0h were determined and compared. RESULTS: GMRs for both test meals were within the international standard references for solid GES. Compared to EWM, Vital® exhibited significantly lower GMRs (faster emptying) from 0.5 to 3 h (all P < 0.001) but comparable at 4 h (P = 0.153). Similar observations were found for the model-based T1/2 and the different Tlag thresholds (all P < 0.001). Furthermore, IMD0h was found to be lower with Vital®, indicating lower gastric accommodation (faster antral filling) immediately post-ingestion (P < 0.001). Both test meals showed significant moderate-to-strong positive associations at the late-phase GE (GMR 2-4 h, T1/2) (all P < 0.05). CONCLUSIONS: Overall, Vital® is an acceptable alternative test meal to the EWM for GES; however, exercise caution when interpreting early-phase GE. The normative values for global GES parameters and IMD0h are also established.

Nuclear imaging to visualize periodontal inflammation: Findings of a randomized controlled trial.

OBJECTIVE: To investigate non-surgical periodontal therapy by 18F-fluorodeoxyglucose (2-[18 F]FDG) uptake using positron emission tomography (PET) integrated with computed tomography (CT). SUBJECTS: Eighty-five patients with peripheral artery disease and severe periodontitis-randomized into three groups receiving therapy with (PT1; n = 29) or without (PT2; n = 28) systemic antibiotics or no treatment (controls: n = 28)-underwent nuclear imaging at baseline and at 3 months. RESULTS: Clinical inflammation (periodontal inflamed surface area; PISA) did not significantly differ across the groups at baseline (p = 0.395) but was significantly reduced at 3 months (p < 0.001), and significantly more so in the PT1/PT2 groups than in the control group (p < 0.001/=0.025) and in the PT1 than in the P2 group (p = 0.001). Radiotracer uptake was measured in both jaws using maximum and mean 'standardized uptake values' (SUVmax , SUVmean ) and 'target-to-background ratios' (TBRmax , TBRmean ). At 3 months, reductions were relatively small in absolute numbers and fell short of revealing correlations with PISA or significant differences across the groups. Still, they were very consistent in both treatment groups, whereas reductions were not consistently seen in the control group. CONCLUSIONS: 2-[18 F]FDG PET/CT scans did reflect the clinical effects of periodontal treatment very consistently but, for reasons yet to be clarified, less closely than expected.

What We Know about and What Is New in Primary Aldosteronism.

Primary aldosteronism (PA), a significant and curable cause of secondary hypertension, is seen in 5-10% of hypertensive patients, with its prevalence contingent upon the severity of the hypertension. The principal aetiologies of PA include bilateral idiopathic hypertrophy (BIH) and aldosterone-producing adenomas (APAs), while the less frequent causes include unilateral hyperplasia, familial hyperaldosteronism (FH) types I-IV, aldosterone-producing carcinoma, and ectopic aldosterone synthesis. This condition, characterised by excessive aldosterone secretion, leads to augmented sodium and water reabsorption alongside potassium loss, culminating in distinct clinical hallmarks: elevated aldosterone levels, suppressed renin levels, and hypertension. Notably, hypokalaemia is present in only 28% of patients with PA and is not a primary indicator. The association of PA with an escalated cardiovascular risk profile, independent of blood pressure levels, is notable. Patients with PA exhibit a heightened incidence of cardiovascular events compared to counterparts with essential hypertension, matched for age, sex, and blood pressure levels. Despite its prevalence, PA remains frequently undiagnosed, underscoring the imperative for enhanced screening protocols. The diagnostic process for PA entails a tripartite assessment: the aldosterone/renin ratio (ARR) as the initial screening tool, followed by confirmatory and subtyping tests. A positive ARR necessitates confirmatory testing to rule out false positives. Subtyping, achieved through computed tomography and adrenal vein sampling, aims to distinguish between unilateral and bilateral PA forms, guiding targeted therapeutic strategies. New radionuclide imaging may facilitate and accelerate such subtyping and localisation. For unilateral adrenal adenoma or hyperplasia, surgical intervention is optimal, whereas bilateral idiopathic hyperplasia warrants treatment with mineralocorticoid antagonists (MRAs). This review amalgamates established and emerging insights into the management of primary aldosteronism.

Radiotracer Development for Fungal-Specific Imaging: Past, Present, and Future.

Invasive fungal infections have become a major challenge for public health, mainly due to the growing numbers of immunocompromised patients, with high morbidity and mortality. Currently, conventional imaging modalities such as computed tomography and magnetic resonance imaging contribute largely to the noninvasive diagnosis and treatment evaluation of those infections. These techniques, however, often fall short when a fast, noninvasive and specific diagnosis of fungal infection is necessary. Molecular imaging, especially using nuclear medicine-based techniques, aims to develop fungal-specific radiotracers that can be tested in preclinical models and eventually translated to human applications. In the last few decades, multiple radioligands have been developed and tested as potential fungal-specific tracers. These include radiolabeled peptides, antifungal drugs, siderophores, fungal-specific antibodies, and sugars. In this review, we provide an overview of the pros and cons of the available radiotracers. We also address the future prospects of fungal-specific imaging.

Clinical Performance of Technetium-99m-Sestamibi SPECT/CT Imaging in Differentiating Oncocytic Tumors From Renal Cell Carcinoma in Routine Clinical Practice.

PURPOSE: Technetium-99m-sestamibi single-photon emission CT/x-ray CT is an emerging clinical tool to differentiate oncocytic tumors from renal cell carcinomas. We report data from a large institutional cohort of patients who underwent technetium-99m-sestamibi scans during evaluation of renal masses. MATERIALS AND METHODS: Patients who underwent technetium-99m-sestamibi single-photon emission CT/x-ray CT between February 2020 and December 2021 were included in the analysis. Scans were defined as "hot" for oncocytic tumor when technetium-99m-sestamibi uptake was qualitatively equivalent or higher between the mass of interest and normal renal parenchyma, suggesting oncocytoma, hybrid oncocytic/chromophobe tumor, or chromophobe renal cell carcinoma. Demographic, pathological, and management strategy data were compared between "hot" and "cold" scans. For individuals who underwent diagnostic biopsy or extirpative procedures, the concordance between radiological findings and pathology was indexed. RESULTS: A total of 71 patients (with 88 masses) underwent technetium-99m-sestamibi imaging with 60 (84.5%) patients having at least 1 "cold" mass on imaging and 11 (15.5%) patients exhibiting only "hot" masses. Pathology was available for 7 "hot" masses, with 1 biopsy specimen (14.3%) being discordant (clear cell renal cell carcinoma). Five patients with "cold" masses underwent biopsy. Out of 5 biopsied masses, 4 (80%) were discordant oncocytomas. Of the extirpated specimens, 35/40 (87.5%) harbored renal cell carcinoma and 5/40 (12.5%) yielded discordant oncocytomas. In sum, 20% of pathologically sampled masses that were "cold" on technetium-99m-sestamibi imaging still harbored oncocytoma/hybrid oncocytic/chromophobe tumor/chromophobe renal cell carcinoma. CONCLUSIONS: Further work is needed to define utility of technetium-99m-sestamibi in real-world clinical practice. Our data suggest this imaging strategy is not yet ready to replace biopsy.

EDB-FN targeted probes for the surgical navigation, radionuclide imaging, and therapy of thyroid cancer.

PURPOSE: Extradomain B of fibronectin (EDB-FN) is a promising diagnostic and therapeutic biomarker for thyroid cancer (TC). Here, we identified a high-affinity EDB-FN targeted peptide named EDBp (AVRTSAD) and developed three EDBp-based probes, Cy5-PEG4-EDBp(Cy5-EDBp), [18F]-NOTA-PEG4-EDBp([18F]-EDBp), and [177Lu]-DOTA-PEG4-EDBp ([177Lu]-EDBp), for the surgical navigation, radionuclide imaging, and therapy of TC. METHODS: Based on the previously identified EDB-FN targeted peptide ZD2, the optimized EDB-FN targeted peptide EDBp was identified by using the alanine scan strategy. Three EDBp-based probes, Cy5-EDBp, [18F]-EDBp, and [177Lu]-EDBp, were developed for fluorescence imaging, positron emission tomography (PET) imaging, and radiotherapy in TC tumor-bearing mice, respectively. Additionally, [18F]-EDBp was evaluated in two TC patients. RESULTS: The binding affinity of EDBp to the EDB fragment protein (Kd = 14.4 ± 1.4 nM, n = 3) was approximately 336-fold greater than that of the ZD2 (Kd = 4839.7 ± 361.7 nM, n = 3). Fluorescence imaging with Cy5-EDBp facilitated the complete removal of TC tumors. [18F]-EDBp PET imaging clearly delineated TC tumors, with high tumor uptake (16.43 ± 1.008%ID/g, n = 6, at 1-h postinjection). Radiotherapy with [177Lu]-EDBp inhibited tumor growth and prolonged survival in TC tumor-bearing mice (survival time of different treatment groups: saline vs. EDBp vs. ABRAXANE vs. [177Lu]-EDBp = 8.00 d vs. 8.00 d vs. 11.67 d vs. 22.33 d, ***p < 0.001). Importantly, the first-in-human evaluation of [18F]-EDBp demonstrated that it had specific targeting properties (SUVmax value of 3.6) and safety. CONCLUSION: Cy5-EDBp, [18F]-EDBp, and [177Lu]-EDBp are promising candidates for the surgical navigation, radionuclide imaging, and radionuclide therapy of TC, respectively.

A novel PSMA targeted dual-function near-infrared fluorescence and PET probe for the image-guided surgery and detection of prostate cancer.

PURPOSE: Prostate-specific membrane antigen (PSMA) is a promising diagnostic biomarker for prostate cancer (PCa). NYM016, a novel small-molecule PSMA-targeted fluorescence probe for the surgical navigation of PCa, was designed in this work. Furthermore, the potential of the PET agent [68Ga]Ga-NYM016 for the radionuclide imaging of PCa was evaluated. METHODS: NYM016 was designed with the near-infrared fluorescent group Cyanine 7 (Cy7) and the chelating group NOTA. The radioactive probe [68Ga]Ga-NYM016 was designed and synthesized on the basis of NYM016. The abovementioned probes were assessed in PSMA-positive xenograft-bearing models and patients diagnosed with PCa. RESULTS: NYM016 obviously aggregated in the tumor site of the mouse model, and its fluorescence intensity was stable within 24 h. NYM016 was well-tolerated, and no adverse events were found in the clinical study. Moreover, it was also observed in the excised lesions from the patient with PCa, and its fluorescence aggregated at the same site where PSMA was highly expressed. In addition, the PSMA xenograft demonstrated intense [68Ga]Ga-NYM016 uptake at 2.5 min after injection. At 3 h after injection, [68Ga]Ga-NYM016 uptake by the PSMA xenograft gradually increased to 6.40 ± 0.19%ID/g, which was higher that by the blocked and negative groups (2.28 ± 0.07%ID/g, P < 0.05; 2.28 ± 0.22%ID/g, P < 0.05). In the clinical study, [68Ga]Ga-NYM016 was well-tolerated and no adverse events were observed. Substantial accumulation was observed in primary and metastatic lesions in a patient with recurrence with the maximum standardized uptake value of 18.93. Meanwhile, negative [68Ga]Ga-NYM016 uptake was observed at the prostate site of a patient with prostatitis. CONCLUSION: The novel fluorescence probe NYM016 and the radioactive tracer [68Ga]Ga-NYM016 are promising candidates for the surgical navigation and radionuclide imaging of PCa, respectively. TRIAL REGISTRATION: The clinical evaluation of this study was registered at Clinicaltrial.gov (NCT05623878) on 21 Dec, 2022.

An artificial intelligence framework for the diagnosis of prosthetic joint infection based on 99mTc-MDP dynamic bone scintigraphy.

OBJECTIVES: Dynamic bone scintigraphy (DBS) is the first widely reliable and simple imaging modality in nuclear medicine that can be used to diagnose prosthetic joint infection (PJI). We aimed to apply artificial intelligence to diagnose PJI in patients after total hip or knee arthroplasty (THA or TKA) based on 99mTc-methylene diphosphonate (99mTc-MDP) DBS. METHODS: A total of 449 patients (255 THAs and 194 TKAs) with a final diagnosis were retrospectively enrolled and analyzed. The dataset was divided into a training and validation set and an independent test set. A customized framework composed of two data preprocessing algorithms and a diagnosis model (dynamic bone scintigraphy effective neural network, DBS-eNet) was compared with mainstream modified classification models and experienced nuclear medicine specialists on corresponding datasets. RESULTS: In the fivefold cross-validation test, diagnostic accuracies of 86.48% for prosthetic knee infection (PKI) and 86.33% for prosthetic hip infection (PHI) were obtained using the proposed framework. On the independent test set, the diagnostic accuracies and AUC values were 87.74% and 0.957 for PKI and 86.36% and 0.906 for PHI, respectively. The customized framework demonstrated better overall diagnostic performance compared to other classification models and showed superiority in diagnosing PKI and consistency in diagnosing PHI compared to specialists. CONCLUSION: The customized framework can be used to effectively and accurately diagnose PJI based on 99mTc-MDP DBS. The excellent diagnostic performance of this method indicates its potential clinical practical value in the future. KEY POINTS: • The proposed framework in the current study achieved high diagnostic performance for prosthetic knee infection (PKI) and prosthetic hip infection (PHI) with AUC values of 0.957 and 0.906, respectively. • The customized framework demonstrated better overall diagnostic performance compared to other classification models. • Compared to experienced nuclear medicine physicians, the customized framework showed superiority in diagnosing PKI and consistency in diagnosing PHI.

Usefulness of gallium-67 scintigraphy for evaluating the histopathological activity in interstitial nephritis.

BACKGROUND: Interstitial nephritis is a common cause of renal failure. Gallium-67 scintigraphy is reportedly useful for diagnosing interstitial nephritis; however, its ability to assess disease activity remains unknown. We aimed to analyze the relationship between the renal uptake of gallium-67 and the disease activity in interstitial nephritis. METHODS: We retrospectively analyzed the data of patients who underwent gallium-67 scintigraphy at a hospital in Tokyo. The renal uptake adjusted for the soft tissues beneath the kidneys was semi-quantitatively evaluated. We compared the renal uptake levels between patients clinically diagnosed with and without interstitial nephritis. Among those undergoing renal biopsy, we evaluated the predictive ability of gallium-67 scintigraphy and analyzed the renal uptake levels regarding the disease activity through a histopathological analysis. RESULTS: We included 143 patients; among them, 30, 17, and 96 patients were clinically diagnosed with interstitial nephritis, other kidney diseases, and non-kidney diseases, respectively. The renal uptake of gallium-67 was the highest among patients with interstitial nephritis. Among the 25 patients who underwent renal biopsy, 15 were pathologically diagnosed with interstitial nephritis. The renal uptake levels showed a high discriminative ability (C-statistic: 0.83). Furthermore, net reclassification improvement with the addition of gallium-67 scintigraphy to N-acetyl-ß-D-glucosaminidase for the prediction of interstitial nephritis was 1.14. Histopathological analysis revealed a positive correlation between renal uptake and inflammation in the cortex and peritubular capillaries. CONCLUSIONS: This study confirmed the diagnostic value and potential usefulness of gallium-67 scintigraphy for evaluating interstitial nephritis.

Ancillary radionuclide perfusion studies in the determination of death by neurologic criteria: methods, interpretation, and lexicon-a user guide for the clinician.

Radionuclide perfusion studies have an established ancillary role in determination of death by neurologic criteria (DNC). While critically important, these examinations are not well understood by individuals outside of the imaging specialties. The purpose of this review is to clarify relevant concepts and nomenclature and provide a lexicon of relevant terminology of value to non-nuclear medicine practitioners who wish to better understand these examinations. Radionuclides were first employed to evaluate cerebral blood flow in 1969. Radionuclide DNC examinations that use lipophobic radiopharmaceuticals (RPs) entail a flow phase followed immediately by blood pool images. On flow imaging, presence of intracranial activity within the arterial vasculature is scrutinized following arrival of the RP bolus into the neck. Lipophilic RPs designed for functional brain imaging were introduced to nuclear medicine in the 1980s and were engineered to cross the blood-brain-barrier and be retained in the parenchyma. The lipophilic RP 99mTc-hexamethylpropyleneamine oxime (99mTc-HMPAO) was first used as an ancillary investigation in DNC in 1986. Examinations using lipophilic RPs entail both flow and parenchymal phase images. According to some guidelines, parenchymal phase uptake should be assessed by tomographic imaging, while other investigators consider simple planar imaging sufficient. Findings of perfusion on either the flow or parenchymal phase of the examination effectively precludes DNC. If the flow phase is omitted or somehow compromised, the parenchymal phase remains sufficient for DNC. A priori, parenchymal phase imaging is superior to flow phase imaging for several reasons and lipophilic RPs are favoured over lipophobic RPs in that both flow and parenchymal phase imaging are performed. Disadvantages of lipophilic RPs are increased cost and the need to procure them from a central laboratory, which can prove difficult, especially outside usual working hours. According to most current guidelines, both lipophilic and lipophobic RP categories are acceptable for use in ancillary investigations in DNC, with a growing overt preference for studies using the lipophilic RPs based on their ability to capture the parenchymal phase. The new adult and pediatric Canadian recommendations favour use of lipophilic RPs to variable degrees, specifically 99mTc-HMPAO, the lipophilic moiety which has undergone the greatest validation. Although ancillary use of radiopharmaceuticals is quite settled in multiple DNC guidelines and best practices, several areas of further research remain open to investigation. Examens auxiliaires de perfusion nucléaire pour la détermination du décès selon des critères neurologiques : méthodes, interprétation et lexique-un guide de l'utilisateur à l'intention du clinicien.

RéSUMé: Les examens de la perfusion nucléaire jouent un rôle auxiliaire bien établi dans la détermination du décès selon des critères neurologiques (DCN). Bien qu'ils soient d'une importance cruciale, ces examens ne sont pas bien compris par les personnes en dehors des spécialités d'imagerie. Le but de cette revue est de clarifier les concepts et la nomenclature pertinents et de fournir un lexique de terminologie pertinente utile aux praticiens non spécialisés en médecine nucléaire qui souhaitent mieux comprendre ces examens. Les radionucléides ont été utilisés pour la première fois pour évaluer la circulation sanguine cérébrale en 1969. Les examens de DCN par radionucléides qui utilisent des produits radiopharmaceutiques (RP) lipophobes impliquent une phase de circulation suivie immédiatement d'images de pool sanguin. Sur l'imagerie en circulation, la présence d'une activité intracrânienne dans le système vasculaire artériel est examinée après l'arrivée du bolus de RP dans le cou. Les RP lipophiles conçus pour l'imagerie cérébrale fonctionnelle ont été introduits en médecine nucléaire dans les années 1980 et ont été conçus pour franchir la barrière hémato-encéphalique et être retenus dans le parenchyme. Le RP lipophile 99mTc-hexaméthylpropylèneamine-oxime (99mTc-HMPAO) a été utilisé pour la première fois comme examen auxiliaire pour le DCN en 1986. Les examens utilisant des RP lipophiles impliquent à la fois des images de circulation et de phase parenchymateuse. Selon certaines lignes directrices, l'absorption durant la phase parenchymateuse devrait être évaluée par imagerie tomographique, tandis que d'autres chercheurs considèrent qu'une imagerie planaire simple suffit. Les résultats de perfusion sur la phase de circulation ou la phase parenchymateuse de l'examen excluent effectivement un DCN. Si la phase de circulation est omise ou compromise d'une manière ou d'une autre, la phase parenchymateuse reste suffisante pour établir un DCN. A priori, l'imagerie en phase parenchymateuse est supérieure à l'imagerie en phase de circulation pour plusieurs raisons et les RP lipophiles sont privilégiés par rapport aux RP lipophobes parce que l'imagerie en circulation et en phase parenchymateuse sont toutes deux réalisées. Les inconvénients des RP lipophiles sont l'augmentation des coûts et la nécessité de les obtenir auprès d'un laboratoire central, ce qui peut s'avérer difficile, surtout en dehors des heures de travail habituelles. Selon la plupart des lignes directrices actuelles, les catégories de RP lipophiles et lipophobes sont toutes deux acceptables pour une utilisation dans les examens auxiliaires pour un DCN, avec une préférence manifeste croissante pour les études utilisant les RP lipophiles en fonction de leur capacité à capturer la phase parenchymateuse. Les nouvelles recommandations canadiennes pour adultes et enfants privilégient l'utilisation de RP lipophiles à des degrés variables, en particulier le 99mTc-HMPAO, le fragment lipophile qui a subi la plus grande validation. Bien que l'utilisation auxiliaire des produits radiopharmaceutiques soit tout à fait établie dans de multiples lignes directrices et meilleures pratiques de DCN, plusieurs domaines de recherche supplémentaires restent ouverts à l'étude.

Ultrafast cadmium-zinc-telluride-based renal single-photon emission computed tomography: clinical validation.

BACKGROUND: One of the main limitations of 99mtechnetium-dimercaptosuccinic acid (DMSA) scan is the long acquisition time. OBJECTIVE: To evaluate the feasibility of short DMSA scan acquisition times using a cadmium-zinc-telluride-based single-photon emission computed tomography (SPECT) system in children. MATERIALS AND METHODS: The data of 27 children (median age: 4 years; 16 girls) who underwent DMSA SPECT were retrospectively analyzed. Both planar and SPECT DMSA were performed. SPECT images were analyzed using coronal-simulated planar two-dimensional images. A reduction in SPECT acquisition time was simulated to provide 4 series (SPECT-15 min, SPECT-10 min, SPECT-5 min and SPECT-2.5 min). A direct comparison of the planar and SPECT series was performed, including semi-quantification reproducibility, image quality (mean quality score on a scale of 0 to 2) and inter- and intra-observer reproducibility of the scintigraphic patterns. RESULTS: The overall image quality score (± standard deviation) was 1.3 (± 0.6) for the planar data set, 1.6 (± 0.5) for the SPECT-15 min data set, 1.4 (± 0.5) for the SPECT-10 min data set, 1.0 (± 0.5) for the SPECT-5 min data set and 0.6 (± 0.6) for the SPECT-2.5 min data set. Median Kappa coefficients for inter-observer agreement between planar and SPECT images were greater than 0.83 for all series and all readers except one reader for the SPECT-2.5 min series (median Kappa coefficient = 0.77). CONCLUSION: Shortening SPECT acquisitions to 5 min is feasible with minimal impact on images in terms of quality and reproducibility.

The relationship between 18F-FCH uptake intensity and cell content in parathyroid lesions.

PURPOSE: To investigate the relationship between cell content and histopathological features of parathyroid lesions and 18F-FCH uptake intensity on PET/CT images. METHODS: Patients with primary hyperparathyroidism (age > 18) who were referred to 18F-FCH PET/CT were involved. All patients underwent parathyroidectomy. Correlation of SUVmax with following factors were statistically analysed: serum PTH, Ca, P levels and histopathological parameters, total absolute amounts of chief cell, oxyphyllic cell and clear cell components calculated by the multiplication of the volume of the parathyroid lesion and the percentage of each type of cell content (called as Absolutechief, Absoluteoxyphyllic and Absoluteclear reflecting the total amount of each cell group). RESULTS: A total of 34 samples from 34 patients (6M, 28F, mean age: 53.32 ± 15.15, min: 14, max: 84) who had a positive 18F-FCH PET/CT localizing at least one parathyroid lesion were involved. In the whole study group, SUVmax was found to be correlated with the greatest diameter and volume of the lesion and Absolutechief (p = 0.004, p = 0.002 and p = 0.035, respectively). In the subgroup analysis of 28 samples with longest diameter > 1 cm, the correlation between SUVmax and Absolutechief remained significant (p = 0.036) and correlation between SUVmax and volume and longest diameter became stronger (p = 0.011 and p > 0.001, respectively). No correlation was found between SUVmax and Absoluteoxyphyllic or Absoluteclear. CONCLUSIONS: There might be a relationship between 18F-FCH uptake intensity and chief cell content in patients with parathyroid adenoma. Further studies with larger patient groups would be beneficial to support the data.

Radioiodination, purification, and evaluation of antihuman tumor-derived immunoglobulin G light chain monoclonal antibody in tumor-bearing nude mice.

We report the synthesis and biological evaluation of 131 I-labeled antihuman tumor-derived immunoglobulin G (IgG) light chain monoclonal antibody (4E9) ([131 I]I-4E9) as a promising probe for tumor imaging. [131 I]I-4E9 was synthesized in radiochemical yield of 89.9 ± 4.7% with radiochemical purity of more than 99%. [131 I]I-4E9 showed high stability in normal saline and human serum. In cell uptake studies, [131 I]I-4E9 exhibited favorable binding affinity and high specificity in HeLa MR cells. In biodistribution studies, [131 I]I-4E9 showed high tumor uptake, high tumor/non-tumor ratios, and specific binding in BALB/c nu/nu mice bearing human HeLa MR xenografts. Single-photon emission computerized tomography (SPECT) imaging of [131 I]I-4E9 in the HeLa MR xenograft model demonstrated clear visualization of tumor after 48 h and confirmed specific binding in tumor. These findings suggest that [131 I]I-4E9 possesses favorable biological characteristics and warrants further investigation as a prospective probe for imaging and treatment of cancers.

A liposomal radionanoformulation for targeted drug delivery and real time monitoring by radionuclide imaging for HER2 overexpressing cancers.

Liposomal formulations carrying chemotherapeutic drugs have demonstrated great potential as effective drug delivery systems. Smart nanoformulations decorated with targeting agents and probes are desired for site specific delivery of drugs and real time monitoring. In this study, we aimed to develop liposomal formulation loaded with doxorubicin and tagged with trastuzumab antibody (Ab) for targeting human epidermal growth factor receptor 2 (HER2) positive tumors. Liposomes were prepared by ethanol injection method using modified lipids to conjugate trastuzumab and radiolabel with Tc-99m radioisotope using DTPA for imaging by single photon emission computed tomography (SPECT). Doxorubicin was loaded using the active pH gradient method. The conjugation of Ab to liposomes was validated by SDS-PAGE and MALDI-MS. 99m Tc labeled liposomes encapsulating doxorubicin conjugated with antibody (99m Tc-Lip-Ab-Dox) and 99m Tc labeled liposomes encapsulating doxorubicin (99m Tc-Lip-Dox) were found to be stable in blood plasma and saline using chromatography method. The specificity of 99m Tc-Lip-Ab-Dox against HER2 receptor was evident from cell uptake and inhibition studies. Results also corroborated with confocal microscopy studies. In vivo studies in tumor bearing severe combined immunodeficient mice by SPECT imaging and biodistribution studies revealed higher uptake of 99m Tc-Lip-Ab-Dox in tumor and less accumulation in the liver compared to 99m Tc-Lip-Dox. In conclusion, liposomal nanoformulation for immunotargeting and monitoring of drug delivery was successfully formulated and evaluated. Encouraging results in preclinical studies were obtained with the radioformulation. Such smart radioformulations will not only serve the purpose of site-specific controlled release of drugs at the target site but also aid in optimizing the drug doses and schedule of cancer treatment by monitoring pharmacokinetics.

In Vivo Trafficking of the Anticancer Drug Tris(8-Quinolinolato) Gallium (III) (KP46) by Gallium-68/67 PET/SPECT Imaging.

KP46 (tris(hydroxyquinolinato)gallium(III)) is an experimental, orally administered anticancer drug. Its absorption, delivery to tumours, and mode of action are poorly understood. We aimed to gain insight into these issues using gallium-67 and gallium-68 as radiotracers with SPECT and PET imaging in mice. [67Ga]KP46 and [68Ga]KP46, compared with [68Ga]gallium acetate, were used for logP measurements, in vitro cell uptake studies in A375 melanoma cells, and in vivo imaging in mice bearing A375 tumour xenografts up to 48 h after intravenous (tracer level) and oral (tracer and bulk) administration. 68Ga was more efficiently accumulated in A375 cells in vitro when presented as [68Ga]KP46 than as [68Ga]gallium acetate, but the reverse was observed when intravenously administered in vivo. After oral administration of [68/67Ga]KP46, absorption of 68Ga and 67Ga from the GI tract and delivery to tumours were poor, with the majority excreted in faeces. By 48 h, low but measurable amounts were accumulated in tumours. The distribution in tissues of absorbed radiogallium and octanol extraction of tissues suggested trafficking as free gallium rather than as KP46. We conclude that KP46 likely acts as a slow releaser of gallium ions which are inefficiently absorbed from the GI tract and trafficked to tissues, including tumour and bone.

The emerging role of radionuclide molecular imaging of HER2 expression in breast cancer.

Targeting of human epidermal growth factor type 2 (HER2) using monoclonal antibodies, antibody-drug conjugates and tyrosine kinase inhibitors extends survival of patients with HER2-expressing metastatic breast cancer. High expression of HER2 is a predictive biomarker for such specific treatment. Accurate determination of HER2 expression level is necessary for stratification of patients to targeted therapy. Non-invasive in vivo radionuclide molecular imaging of HER2 has a potential of repetitive measurements, addressing issues of heterogeneous expression and conversion of HER2 status during disease progression or in response to therapy. Imaging probes based of several classes of targeting proteins are currently in preclinical and early clinical development. Both preclinical and clinical data suggest that the most promising are imaging agents based on small proteins, such as single domain antibodies or engineered scaffold proteins. These agents permit a very specific high-contrast imaging at the day of injection.

Myocardial perfusion SPECT findings in postCOVID period.

PURPOSE: To investigate if (i) the risk of ischemia on myocardial perfusion scan (MPS), (ii) number of coronary angiographies (CAG) performed, and (iii) necessity for invasive (stent implantation or coronary artery bypass grafting (CABG)) or medical treatment increased in patients infected with COVID-19. METHODS: Patients who were referred to MPS between August 2020 and April 2021 with a history of active symptomatic COVID-19 infection (confirmed by PCR positivity) in the last 6 months were involved in the study group. Age-and gender-matched control group was composed of randomly chosen patients who attended for MPS between January 2019 and September 2019, before pandemic. Frequency of ischemia, CAG, and invasive or medical treatments were compared between groups. RESULTS: Ischemia was reported more frequently in the study group (p < 0.001). In clinical evaluation, regardless of the MPS results, the necessity for invasive evaluation with CAG and treatment (either medical therapy or invasive interventions) was higher in the study group (p = 0.006 and p = 0.015). It was also true for patients with abnormal MPS results (p = 0.008 and p = 0.024) but not for the patients with ischemia (p = 0.29 and p = 0.06). CONCLUSION: There exists a significant increase in the frequency of ischemia on MPS, undergoing CAG, stent implantation or CABG, and initiation of medical therapy in patients with a history of COVID-19 infection in the last 6 months. MPS is a reliable method in patients who present with cardiovascular symptoms in the late COVID period.