Purpose
Sentinel lymph node (SLN) biopsy is a staging procedure in the management of cutaneous malignancies of the head. The ideal radiopharmaceutical is controversial. This study aimed to compare
...99m
TcTc-tilmanocept (TcTM) with
99m
TcTc-sulphur colloid (TcSC) and
99m
TcTc-albumin colloid (TcAC) for SLN detection in the head and neck region.
Methods
Data from 62 patients with cutaneous malignancies of the head who were injected with TcTM, TcSC, or TcAC before SLN imaging (SLN-I) and SLN excision (SLN-E) between 2012 and 2021 were retrospectively analysed. SLN-I was performed using planar lymphoscintigraphy and SPECT/CT, and a gamma probe was used for SLN-E. The SLN-I localisation rate (patients with SLNs) and degree (SLN number) and SLN-E relocalisation rate (patients with SLNs) and ratio (SLN number in SLN-E/SLN number in SLN-I) were compared between TcTM, TcSC, and TcAC.
Results
TcTM showed similar SLN-I localisation rates for primaries in the anterior and posterior head region compared with TcSC (84.6% vs. 72.4%,
p
=0.680; both 100.0%) and TcAC (84.6% vs. 75.0%,
p
=1.000; both 100.0%). The SLN-I localisation degree for TcTM was higher for primaries in the anterior head region and similar for primaries in the posterior head region compared with TcSC (3.2 vs. 2.3,
p
=0.034; and 1.8 vs. 2.2,
p
=0.506) and TcAC (3.2 vs. 2.0,
p
=0.038; and 1.8 vs. 2.7,
p
=0.329). The SLN-E relocalisation rates and ratios were similar for all.
Conclusion
On the basis of a limited study design that compared three different tracers in three different patient groups, TcTM showed comparable overall performance to TcSC and TcAC.
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•Chlorambucil was linked to HYNIC to form HYNIC-chlorambucil conjugate.•HYNIC-chlorambucil labeled with 99mTcTc, with > 95 % radiochemical purity.•Appreciable tumor uptake with ...gradual clearance with time observed.•Increasing tumor-to-blood ratio with time suggests tumor selective retention.•Biological behaviour of 99mTcTc-chlorambucil is influenced by the BFCA.
Chlorambucil is an alkylating drug that finds application towards chemotherapy of different types of cancers. In order to explore the possibility of utilization of this drug as an imaging agent for early diagnosis of solid tumors, attempt was made to synthesize a 99mTc complex of chlorambucil and evaluate its potential in tumor bearing small animal model. HYNIC-chlorambucil was synthesized by conjugation of HYNIC with chlorambucil via an ethylenediamine linker. All the intermediates and final product were purified and characterized by standard spectroscopic techniques viz. FT-IR, 1H/13C-NMR as well as by mass spectrometry. HYNIC-chlorambucil conjugate was radiolabeled with 99mTcTc and found to be formed with > 95 % radiochemical purity via RP-HPLC studies. The partition coefficient (Log10Po/w) of the synthesized complex was found to be −0.78 ± 0.25 which indicated the moderate hydrophilic nature for the complex. Biological behaviour of 99mTcTc-HYNIC-chlorambucil, studied in fibrosarcoma bearing Swiss mice, revealed a tumor uptake of about 4.16 ± 1.52 %IA/g at 30 min post-administration, which declined to 1.91 ± 0.13 % IA/g and 1.42 ± 0.14 %IA/g at 1 h and 2 h post-administration, respectively. A comparison of different 99mTcTc-chlorambucil derivatives (reported in the contemporary literature) formulated using different methodologies revealed that tumor uptake and pharmacokinetics exhibited by these agents strongly depend on the lipophilicity/hydrophilicity of such agents, which in turn is dependent on the bifunctional chelators used for formulating the radiolabeled chlorambucils.
The EANM practice guidelines for parathyroid imaging Petranović Ovčariček, Petra; Giovanella, Luca; Carrió Gasset, Ignasi ...
European journal of nuclear medicine and molecular imaging,
08/2021, Letnik:
48, Številka:
9
Journal Article
Recenzirano
Odprti dostop
Introduction
Nuclear medicine parathyroid imaging is important in the identification of hyperfunctioning parathyroid glands in primary hyperparathyroidism (pHPT), but it may be also valuable before ...surgical treatment in secondary hyperparathyroidism (sHPT). Parathyroid radionuclide imaging with scintigraphy or positron emission tomography (PET) is a highly sensitive procedure for the assessment of the presence and number of hyperfunctioning parathyroid glands, located either at typical sites or ectopically. The treatment of pHPT is mostly directed toward minimally invasive parathyroidectomy, especially in cases with a single adenoma. In experienced hands, successful surgery depends mainly on the exact preoperative localization of one or more hyperfunctioning parathyroid adenomas. Failure to preoperatively identify the hyperfunctioning parathyroid gland challenges minimally invasive parathyroidectomy and might require bilateral open neck exploration.
Methods
Over a decade has now passed since the European Association of Nuclear Medicine (EANM) issued the first edition of the guideline on parathyroid imaging, and a number of new insights and techniques have been developed since. The aim of the present document is to provide state-of-the-art guidelines for nuclear medicine physicians performing parathyroid scintigraphy, single-photon emission computed tomography/computed tomography (SPECT/CT), positron emission tomography/computed tomography (PET/CT), and positron emission tomography/magnetic resonance imaging (PET/MRI) in patients with pHPT, as well as in those with sHPT.
Conclusion
These guidelines are written and authorized by the EANM to promote optimal parathyroid imaging. They will assist nuclear medicine physicians in the detection and correct localization of hyperfunctioning parathyroid lesions.
Technetium-labeled cardiac scintigraphy (i.e., Tc-PYP scan) has been repurposed for the diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CM). Validated in cohorts of patients with heart ...failure and echocardiographic and/or cardiac magnetic resonance imaging findings suggestive of cardiac amyloidosis, cardiac scintigraphy can confirm the diagnosis of ATTR-CM only when combined with blood and urine testing to exclude a monoclonal protein. Multisocietal guidelines support the nonbiopsy diagnosis of ATTR-CM using cardiac scintigraphy, yet emphasize its use in the appropriate clinical context and the crucial need to rule out light chain amyloid cardiomyopathy. Although increased awareness of ATTR-CM and the advent of effective therapy have led to rapid adoption of diagnostic scintigraphy, there is heterogeneity in adherence to consensus guidelines. This perspective outlines clinical scenarios wherein findings on technetium-labeled cardiac scintigraphy have been misinterpreted, reviews causes of false-negative and false-positive results, and provides strategies to avoid costly and potentially fatal misdiagnoses.
: The frequent overexpression of gastrin-releasing peptide receptors (GRPRs) in human cancers provides the rationale for delivering clinically useful radionuclides to tumor sites using peptide ...carriers. Radiolabeled GRPR antagonists, besides being safer for human use, have often shown higher tumor uptake and faster background clearance than agonists. We herein compared the biological profiles of the GRPR-antagonist-based radiotracers
TcTc-N
-PEGx-DPhe
,Leu-NHEt
BBN(6-13) (N
: 6-(carboxy)-1,4,8,11-tetraazaundecane; PEG: polyethyleneglycol): (i)
TcTc-DB7 (x = 2), (ii)
TcTc-DB13 (x = 3), and (iii)
TcTc-DB14 (x = 4), in GRPR-positive cells and animal models. The impact of in situ neprilysin (NEP)-inhibition on in vivo stability and tumor uptake was also assessed by treatment of mice with phosphoramidon (PA).
: The GRPR affinity of DB7/DB13/DB14 was determined in PC-3 cell membranes, and cell binding of the respective
TcTc-radioligands was assessed in PC-3 cells. Each of
TcTc-DB7,
TcTc-DB13, and
TcTc-DB14 was injected into mice without or with PA coinjection and 5 min blood samples were analyzed by HPLC. Biodistribution was conducted at 4 h postinjection (pi) in severe combined immunodeficiency disease (SCID) mice bearing PC-3 xenografts without or with PA coinjection.
: DB7, -13, and -14 displayed single-digit nanomolar affinities for GRPR. The uptake rates of
TcTc-DB7,
TcTc-DB13, and
TcTc-DB14 in PC-3 cells was comparable and consistent with a radioantagonist profile. The radiotracers were found to be ≈70% intact in mouse blood and >94% intact after coinjection of PA. Treatment of mice with PA enhanced tumor uptake.
: The present study showed that increase of PEG-spacer length in the
TcTc-DB7-
TcTc-DB13-
TcTc-DB14 series had little effect on GRPR affinity, specific uptake in PC-3 cells, in vivo stability, or tumor uptake. A significant change in in vivo stability and tumor uptake was observed only after treatment of mice with PA, without compromising the favorably low background radioactivity levels.
Exosomes are secreted into the extracellular space by most cell types and contain various molecular constituents, which play roles in many biological processes. Adipose‐derived mesenchymal stem cells ...(ADSCs) can differentiate into a variety of cell types and secrete a series of paracrine factors through exosomes. ADSC‐derived exosomes have shown diagnostic and therapeutic potential in many clinical diseases. The molecular components are critical for their mechanisms. Several methods have been developed for exosome purification, including ultracentrifugation, ultrafiltration, density gradient purification, size‐based isolation, polymer precipitation and immuno‐affinity purification. Thus, we employed four methods to isolate exosomes from the hADSC culture medium, including ultracentrifugation, size exclusion chromatography, ExoQuick‐TC precipitation and ExoQuick‐TC ULTRA isolation. Following exosome isolation, we performed quantitative proteomic analysis of the exosome proteins using isobaric tags for relative and absolute quantification (iTRAQ) labelling, combined with 2D‐LC‐MS/MS. There were 599 universal and 138 stably expressed proteins in hADSC‐derived exosomes. We proved that these proteins were potential hADSC‐derived exosomes markers, including CD109, CD166, HSPA4, TRAP1, RAB2A, RAB11B and RAB14. From the quantitative proteomic analysis, we demonstrated that hADSC‐derived exosome protein expression varied, with lipopolysaccharide (LPS) treatment, in the different isolation methods. Pathway analysis and proliferation, migration and endothelial tube formation assays showed varying effects in cells stimulated with hADSC‐derived exosomes from different isolation methods. Our study revealed that different isolation methods might introduce variations in the protein composition in exosomes, which reflects their effects on biological function. The pros and cons of these methods are important points to consider for downstream research applications.
The radially outward propagating diurnal signal in the upper‐level clouds (diurnal pulse) is a prominent cyclical feature of tropical cyclones (TCs). This study examines relationships between diurnal ...pulses and TC intensity changes using satellite Infrared data from 2001 to 2018. The occurrence and duration of diurnal pulses 24 hr prior to or during TC intensity change are strongly correlated with TC intensification rate. Rapidly intensifying (RI) TCs have a markedly higher frequency (60%–80%) of very long‐duration pulse (≥15 hr) and significantly longer mean pulse duration than steady‐state (40%–50%) and gradually intensifying TCs (50%–60%). Long‐duration pulses are infrequent in weakening TCs (20%–30%). Diurnal pulse frequency and duration are highly correlated with the initial cloud‐top cooling rate and very cold‐cloud fraction in the inner core, but less related to the initial TC intensity. In short, strong diurnal pulsing of cold clouds is an evident signature prior to or during the RI of TCs.
Plain Language Summary
Clouds and precipitation in tropical cyclones (TCs) sometimes have an evident diurnal cycle, just like the regular daily weather systems. One dramatic feature is that cloud tops of the TCs oscillate like a wave propagating from the storm center out to several hundred kilometres over the course of the day, so called diurnal wave. This study uses infrared measurements from global satellites to study the relationships between the diurnal wave of cloud tops and the change of the TC's intensity. Results show that there are close relationships between diurnal waves and the intensification of TCs. Diurnal waves are more likely to occur in intensifying TCs than steady‐state or weakening TCs. The occurrence frequency and duration of the diurnal waves increase linearly with the intensification rate of TCs, for instance, rapidly intensifying TCs have significantly stronger and longer‐lived diurnal waves than slowly intensifying TCs. The frequency and duration of diurnal waves usually increase 24 hr prior to or during the TC's intensification, while they are relatively invariant after TC intensifying. In short, the diurnal wave of cloud tops is a potential predictor or indicator for the evolution of the TC's intensity and provides a new perspective for the study of TC intensity change.
Key Points
Tropical cyclones (TCs) intensification rate is strongly correlated with the frequency and duration of the diurnal pulse of upper‐level clouds in TCs
Very long‐duration diurnal pulses are markedly more frequent in rapidly intensifying TCs than steady‐state or gradually intensifying TCs
Occurrence and duration of the diurnal pulse is the best correlated with the initial inner‐core cloud‐top cooling rate
Technetium mainly forms during artificial nuclear fission; it exists primarily as TcO4(-) in nuclear waste, and it is among the most hazardous radiation-derived contaminants because of its long ...half-life (t1/2 = 2.13 × 10(5) years) and environmental mobility. The high water solubility of TcO4(-) (11.3 mol L(-1) at 20 °C) and its ability to readily migrate within the upper layer of the Earth's crust make it particularly hazardous. Several types of materials, namely resins, molecular complexes, layered double hydroxides, and pure inorganic and metal-organic materials, have been shown to be capable of capturing TcO4(-) (or other oxoanions) from solution. In this review, we give a brief description about the types of materials that have been used to capture TcO4(-) and closely related oxyanions so far and discuss the possibility of using metal-organic frameworks (MOFs) as next-generation ion-exchange materials for the stated application. In particular, with the advent of ultra-stable MOF materials, in conjunction with their chemical tunability, MOFs can be applied to capture these oxyanions under real-life conditions.
In the treatment of peritoneal carcinomatosis, systemic chemotherapy is not quite effective due to the poor penetration of cytotoxic agents into the peritoneal cavity, whereas intraperitoneal ...administration of chemotherapeutic agents is generally accompanied by quick absorption of the free drug from the peritoneum. Local delivery of drugs with controlled-release delivery systems like liposomes could provide sustained, elevated drug levels and reduce local and systemic toxicity. In order to achieve an ameliorated liposomal formulation that results in higher peritoneal levels of the drug and retention, vesicles composed of different phospholipid compositions (distearoyl DSPC; dipalmitoyl DPPC; or dimiristoylphosphatidylcholine DMPC) and various charges (neutral; negative, containing distearoylphosphatidylglycerol DSPG; or positive, containing dioleyloxy trimethylammonium propane DOTAP) were prepared at two sizes of 100 and 1000
nm. The effect of surface hydrophilicity was also investigated by incorporating PEG into the DSPC-containing neutral and charged liposomes. Liposomes were labeled with
99mTc and injected into mouse peritoneum. Mice were then sacrificed at eight different time points, and the percentage of injected radiolabel in the peritoneal cavity and the tissue distribution in terms of the percent of the injected dose/gram of tissue (%ID/g) were obtained.
The ratio of the peritoneal AUC to the free label ranged from a minimum of 4.95 for DMPC/CHOL (cholesterol) 100
nm vesicles to a maximum of 24.99 for DSPC/CHOL/DOTAP 1000
nm (DOTAP 1000) vesicles. These last positively charged vesicles had the greatest peritoneal level; moreover, their level remained constant at approximately 25% of the injected dose from 2 to 48
h. Among the conventional (i.e., without PEG) 100
nm liposomes, the positively charged vesicles again showed the greatest retention. Incorporation of PEG at this size into the lipid structures augmented the peritoneal level, particularly for negatively charged liposomes. The positively charged PEGylated vesicles (DOTAP/PEG 100) had the second-greatest peritoneal level after DOTAP 1000; however, their peritoneal-to-blood AUC ratio was low (3.05).
Overall, among the different liposomal formulations, the positively charged conventional liposomes (100 and 1000
nm) provided greater peritoneal levels and retention. DOTAP/PEG100 may also be a more efficient formulation because this formulation can provide a high level of anticancer drug into the peritoneal cavity and also can passively target the primary tumor.
Peritoneal level and tissue distribution of classical and PEGylated liposomes with different phospholipid compositions and charges at two sizes (100
nm, A; and 1000
nm, B), were investigated after i.p. injection to mice. Positively charged conventional liposomes provided greater peritoneal levels and retention.
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Myocardial uptake of bone tracers has emerged as useful tool for the early detection of transthyretin amyloidosis (ATTR). The prevalence of wild-type ATTR (ATTRwt) in individuals remains to be ...established.
All whole body bone scans performed in individuals ≥ 75 years with no previous clinical suspicion of ATTR were revised in a population-based university hospital over a 7-year period (1509 studies corresponding to 1114 patients; 80.5 ± 4.1 years, 65% males). Positive cardiac uptake was defined according to Perugini score as grade 2 or 3. Heart failure (HF) hospitalizations during the follow-up were obtained from regional administrative databases.
Thirty-one patients ≥ 75 years (2.78%) showed cardiac uptake; compared with those without uptake, these patients were older (85 ± 5 vs. 80 ± 4, p < 0.001) and predominantly males (90% vs. 64%, p = 0.005). The prevalence of cardiac uptake was 3.88% in males and 0.77% in females, and increased with age, reaching 13.9% in males≥85 years (2.7% among females). The estimated prevalence for the European standard population ≥ 75 years was 4.15% in males, 1.03% in females and 2.59% in the general population. HF hospitalizations rates were 14% in patients without uptake and 29% in those with cardiac uptake (p = 0.034). After adjusting for age and gender, cardiac uptake was associated with a higher risk of HF hospitalization (OR 2.60, 95%CI 1.09–5.74, p = 0.022).
Myocardial uptake in bone scan is very prevalent with ageing, mainly affects males and is associated with an increased risk of HF hospitalization. These findings reinforce ATTRwt as a relevant cause of HF in the elderly.
•Over 75 years, 3.88% of males and 0.77% of females had cardiac uptake in bone scan.•Among males over 85 years, prevalence of cardiac uptake reached 13.9%.•Cardiac uptake was associated with a higher risk of HF hospitalization.
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