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The preliminary role of [18F]fluoro-5α-dihydrotestosterone ([18F]FDHT) in identifying receptor status and managing cancer patients is promising. In this work, we compiled studies regarding the ability of [18F]FDHT to predict response to treatment in different stages of drug development. In the chemical development, the androgen receptor (AR) ligands of [18F]FDHT were the candidates evaluated and identified using preclinical methods. High uptake of [18F]FDHT levels was observed in cell lines and xenograft tumours in mice having glucuronidation-competent cells mimicking the sensitive type of castration-resistant prostate cancer (CRPC) treated with androgen deprivation therapy (ADT). In clinical trials, the detection of lesions with [18F]FDHT was in agreement with the standard radiotracer [18F]FDG in advanced prostate cancer (PC) and was even better in AR-positive without glycolytic activity (AR1Glyc0) subtypes, demonstrating the specific role of [18F]FDHT for the detection of tumour localisation. Moreover, the immunohistochemistry (IHC) correlation between [18F]FDHT and AR was stronger than the correlation between [68 Ga]Ga-PSMA-11 and prostate-specific membrane antigen (PSMA), suggesting that [18F]FDHT can be a standalone modality for the monitoring of AR-targeted therapy. [ABSTRACT FROM AUTHOR]

High-resolution Spatiotemporal Biological Imaging by YN s. [Display omitted] • Six novel YN s were synthesized through simple methods. • YN-4, YN-5 and YN-Glu are low cytotoxicity and exhibits good photostability. • The strong electron-donating groups (iodine and methoxyphenyl) introduced as terminal groups of cyanines can enhance brightness under the NIR-IIa window. • YN-4 can clearly visualize microvasculature in subcutaneous and tumor regions of mice, as well as enable real-time imaging of mouse gastrointestinal motility under NIR-IIa window. • The glucose-derived YN-Glu enables imaging of the tumor site in mice in the 1300 nm LP. We propose a novel strategy for tailoring the structure of fluorescent molecules to achieve emission at the tail end of the NIR-II window. The favorable spectroscopic properties and low cytotoxicity of YN s make them powerful tools for bioimaging. Notably, YN-4 exhibits a brightness 2.5 times greater than YN-3 , 6 times that of IR-783, and 5 times that of ICG. This enhanced brightness enabled high-resolution imaging of mouse thoracic and abdominal cavities, tumor vasculature, and real-time monitoring of gastrointestinal motility using YN-4. Furthermore, covalent grafting of glucose onto the YN-Glu scaffold significantly improved tumor-targeting capability and facilitated tracking of glucose metabolism. This work aims to extend the application of fluorescent molecule imaging beyond the NIR-IIa window. [ABSTRACT FROM AUTHOR]

Abstract Background Understanding the regional vascular delivery of particles to tumour sites is a prerequisite for developing new diagnostic and therapeutic composites for treatment of oncology patients. We describe a novel imageable 67Ga-radiolabelled polymer composite that is biocompatible in an animal tumour model and can be used for preclinical imaging investigations of the transit of different sized particles through arterial networks of normal and tumour-bearing organs. Results Radiolabelling of polymer microspheres with 67Ga was achieved using a simple mix and wash method, with tannic acid as an immobilising agent. Final in vitro binding yields after autoclaving averaged 94.7%. In vivo stability of the composite was demonstrated in New Zealand white rabbits by intravenous administration, and intrahepatic artery instillations were made in normal and VX2 tumour implanted rabbit livers. Stability of radiolabel was sufficient for rabbit lung and liver imaging over at least 3 hours and 1 hour respectively, with lung retention of radiolabel over 91%, and retention in both normal and VX2 implanted livers of over 95%. SPECT-CT imaging of anaesthetised animals and planar imaging of excised livers showed visible accumulation of radiolabel in tumours. Importantly, microsphere administration and complete liver dispersal was more easily achieved with 8 μm diameter MS than with 30 μm MS, and the smaller microspheres provided more distinct and localised tumour imaging. Conclusion This method of producing 67Ga-radiolabelled polymer microspheres is suitable for SPECT-CT imaging of the regional vascular delivery of microspheres to tumour sites in animal models. Sharper distinction of model tumours from normal liver was obtained with smaller MS, and tumour resolution may be further improved by the use of 68Ga instead of 67Ga, to enable PET imaging.

Colorectal cancer is the fourth most diagnosed malignancy worldwide and surgery is one of the cornerstones of the treatment strategy. Near-infrared (NIR) fluorescence imaging is a new and upcoming technique, which uses an NIR fluorescent agent combined with a specialised camera that can detect light in the NIR range. It aims for more precise surgery with improved oncological outcomes and a reduction in complications by improving discrimination between different structures. A systematic search was conducted in the Embase, Medline and Cochrane databases with search terms corresponding to 'fluorescence-guided surgery', 'colorectal surgery', and 'colorectal cancer' to identify all relevant trials. The following clinical applications of fluorescence guided surgery for colorectal cancer were identified and discussed: (1) tumour imaging, (2) sentinel lymph node imaging, (3) imaging of distant metastases, (4) imaging of vital structures, (5) imaging of perfusion. Both experimental and FDA/EMA approved fluorescent agents are debated. Furthermore, promising future modalities are discussed. Fluorescence-guided surgery for colorectal cancer is a rapidly evolving field. The first studies show additional value of this technique regarding change in surgical management. Future trials should focus on patient related outcomes such as complication rates, disease free survival, and overall survival. [ABSTRACT FROM AUTHOR]

Purpose: In this study, a novel aluminium-[18F]fluoride (Al18F)-labelled 1,4,7‑triazacyclononane-N,N′,N″-triacetic acid (NOTA)-conjugated fibroblast activation protein inhibitor (FAPI) probe, named Al18F-NOTA-FAPI, was developed for fibroblast activation protein (FAP)-targeted tumour imaging; it could deliver hundreds of millicuries of radioactivity using automated synthesis. The tumour detection efficacy of Al18F-NOTA-FAPI was further validated in both preclinical and clinical translational studies. Methods: The radiolabelling procedure of Al18F-NOTA-FAPI was optimized. Cell uptake and competitive binding assays were completed with the U87MG and A549 cell lines to evaluate the affinity and specificity of the Al18F-NOTA-FAPI probe. The biodistribution, pharmacokinetics, radiation dosimetry and tumour imaging efficacy of the Al18F-NOTA-FAPI probe were researched in healthy Kunming (KM) and/or U87MG model mice. After the approval of the ethical committee, the Al18F-NOTA-FAPI probe was translated into the clinic for PET/CT imaging of the first 10 cancer patients. Results: The radiolabelling yield of Al18F-NOTA-FAPI was 33.8 ± 3.2% using manual synthesis (n = 10), with a radiochemical purity over 99% and the specific activity of 9.3–55.5 MBq/nmol. The whole body effective dose of Al18F-NOTA-FAPI was estimated to be 1.24E − 02 mSv/MBq, which was lower than several other FAPI probes (68Ga-FAPI-04, 68Ga-FAPI-46 and 68Ga-FAPI-74). In U87MG tumour-bearing mice, Al18F-NOTA-FAPI showed good tumour detection efficacy based on the results of micro PET/CT imaging and biodistribution studies. In an organ biodistribution study of patients, Al18F-NOTA-FAPI showed a lower SUVmean than 2-[18F]-fluoro-2-deoxy-D-glucose (2-[18F]FDG) in most organs, especially in the liver (1.1 ± 0.2 vs. 2.0 ± 0.9), brain (0.1 ± 0.0 vs. 5.9 ± 1.3), and bone marrow (0.9 ± 0.1 vs. 1.7 ± 0.4). Meanwhile, Al18F-NOTA-FAPI did not show extensive bone uptake, and was able to detect more lesions than 2-[18F]FDG in the PET/CT imaging of several patients. Conclusion: The Al18F-NOTA-FAPI probe was successfully fabricated and applied in fibroblast activation protein-targeted tumour PET/CT imaging, which showed excellent imaging quality and tumour detection efficacy in U87MG tumour-bearing mice as well as in cancer patients. Trial registration: Chinese Clinical Trial Registry ChiCTR2000038080. Registered 09 September 2020. http://www.chictr.org.cn/showproj.aspx?proj=61192 [ABSTRACT FROM AUTHOR]

Background: Our aim was to evaluate if a recently introduced TOF PET system with digital photon counting technology (Philips Healthcare), potentially providing an improved image quality over analogue systems, can fulfil EANM research Ltd (EARL) accreditation specifications for tumour imaging with FDG-PET/CT. Findings: We have performed a phantom study on a digital TOF PET system using a NEMA NU2-2001 image quality phantom with six fillable spheres. Phantom preparation and PET/CT acquisition were performed according to the European Association of Nuclear Medicine (EANM) guidelines. We made list-mode ordered-subsets expectation maximization (OSEM) TOF PET reconstructions, with default settings, three voxel sizes (4 × 4 × 4 mm, 2 × 2 × 2 mm and 1 × 1 × 1 mm) and with/without point spread function (PSF) modelling. On each PET dataset, mean and maximum activity concentration recovery coefficients (RC and RC) were calculated for all phantom spheres and compared to EARL accreditation specifications. The RCs of the 4 × 4 × 4 mm voxel dataset without PSF modelling proved closest to EARL specifications. Next, we added a Gaussian post-smoothing filter with varying kernel widths of 1-7 mm. EARL specifications were fulfilled when using kernel widths of 2 to 4 mm. Conclusions: TOF PET using digital photon counting technology fulfils EARL accreditation specifications for FDG-PET/CT tumour imaging when using an OSEM reconstruction with 4 × 4 × 4 mm voxels, no PSF modelling and including a Gaussian post-smoothing filter of 2 to 4 mm. [ABSTRACT FROM AUTHOR]

In this review we discuss the development of paramagnetic liposomes incorporating MRI contrast agents and show how these are utilized in cellular imaging in vitro. Bi-functional, bi-modal imaging paramagnetic liposome systems are also described. Next we discuss the upgrading of paramagnetic liposomes into bi-modal imaging neutral nanoparticles for in vivo imaging applications. We discuss the development of such systems and show how paramagnetic liposomes and imaging nanoparticles could be developed as platforms for future multi-functional, multi-modal imaging theranostic nanodevices tailor-made for the combined imaging of early stage disease pathology and functional drug delivery.

Background: For tumour imaging with PET, the literature proposes to administer a patient-specific FDG activity that depends quadratically on a patient's body weight. However, a practical approach on how to implement such a protocol in clinical practice is currently lacking. We aimed to provide a practical method to determine a FDG activity formula for whole-body PET examinations that satisfies both the EANM guidelines and this quadratic relation. Results: We have developed a methodology that results in a formula describing the patient-specific FDG activity to administer. A PET study using the NEMA NU-2001 image quality phantom forms the basis of our method. This phantom needs to be filled with 2.0 and 20.0 kBq FDG/mL in the background and spheres, respectively. After a PET acquisition of 10 min, a reconstruction has to be performed that results in sphere recovery coefficients (RCs) that are within the specifications as defined by the EANM Research Ltd (EARL). By performing reconstructions based on shorter scan durations, the minimal scan time per bed position ( T ) needs to be extracted using an image coefficient of variation (COV) of 15 %. At T , the RCs should be within EARL specifications as well. Finally, the FDG activity (in MBq) to administer can be described by $$ A=c \cdot {w}^2\cdot \frac{T_{\min }}{t} $$ with c a constant that is typically 0.0533 (MBq/kg), w the patient's body weight (in kg), and t the scan time per bed position that is chosen in a clinical setting (in seconds). We successfully demonstrated this methodology using a state-of-the-art PET/CT scanner. Conclusions: We provide a practical method that results in a formula describing the FDG activity to administer to individual patients for whole-body PET examinations, taking into account both the EANM guidelines and a quadratic relation between FDG activity and patient's body weight. This formula is generally applicable to any PET system, using a specified image reconstruction and scan time per bed position. [ABSTRACT FROM AUTHOR]

This review investigated the relative performance of digital breast tomosynthesis (DBT) (alone or with full field digital mammography (FFDM) or synthetic digital mammography) compared with FFDM alone for detecting breast cancer lesions in asymptomatic women. A systematic review was carried out according to systematic reviewing principles provided in the Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy. A protocol was developed a priori . The review was registered with PROSPERO (number CRD42014013949). Searches were undertaken in October 2014. Following selection, five studies were eligible. Higher cancer detection rates were observed when comparing DBT + FFDM with FFDM in two European studies: the summary difference per 1000 screens was 2.43 (95% CI: 1.8 to 3.1). Both European studies found lower false positive rates for individual readers. One found a lower recall rate based on conditional recall. The second study was not designed to compare post-arbitration recall rates between FFDM and DBT + FFDM. One European study presented data on interval cancer rates; sensitivity and specificity for DBT + FFDM were both higher compared to FFDM. One large multicentre US study showed a higher cancer detection rate for DBT + FFDM, while two smaller US studies did not find statistically significant differences. Reductions in recall and false positive rates were observed in the US studies in favour of DBT + FFDM. In comparison to FFDM, DBT, as an adjunct to FFDM, has a higher cancer detection rate, increasing the effectiveness of breast cancer screening. Additional benefits of DBT may also include reduced recalls and, consequently, reduced costs and distress caused to women who would have been recalled. [ABSTRACT FROM AUTHOR]

Purpose: Point-spread function (PSF) or PSF + time-of-flight (TOF) reconstruction may improve lesion detection in oncologic PET, but can alter quantitation resulting in variable standardized uptake values (SUVs) between different PET systems. This study aims to validate a proprietary software tool (EQ.PET) to harmonize SUVs across different PET systems independent of the reconstruction algorithm used. Methods: NEMA NU2 phantom data were used to calculate the appropriate filter for each PSF or PSF+TOF reconstruction from three different PET systems, in order to obtain EANM compliant recovery coefficients. PET data from 517 oncology patients were reconstructed with a PSF or PSF+TOF reconstruction for optimal tumour detection and an ordered subset expectation maximization (OSEM3D) reconstruction known to fulfil EANM guidelines. Post-reconstruction, the proprietary filter was applied to the PSF or PSF+TOF data (PSF or PSF+TOF). SUVs for PSF or PSF+TOF and PSF or PSF+TOF were compared to SUVs for the OSEM3D reconstruction. The impact of potential confounders on the EQ.PET methodology including lesion and patient characteristics was studied, as was the adherence to imaging guidelines. Results: For the 1380 tumour lesions studied, Bland-Altman analysis showed a mean ratio between PSF or PSF+TOF and OSEM3D of 1.46 (95 %CI: 0.86-2.06) and 1.23 (95 %CI: 0.95-1.51) for SUV and SUV, respectively. Application of the proprietary filter improved these ratios to 1.02 (95 %CI: 0.88-1.16) and 1.04 (95 %CI: 0.92-1.17) for SUV and SUV, respectively. The influence of the different confounding factors studied (lesion size, location, radial offset and patient's BMI) was less than 5 %. Adherence to the European Association of Nuclear Medicine (EANM) guidelines for tumour imaging was good. Conclusion: These data indicate that it is not necessary to sacrifice the superior lesion detection and image quality achieved by newer reconstruction techniques in the quest for harmonizing quantitative comparability between PET systems. [ABSTRACT FROM AUTHOR]

Introduction Early detection of pancreatic cancer could save many thousands of lives. Non-invasive diagnostic imaging, including PET with [ 18 F]FDG, has inadequate resolution for detection of small (2–3 mm) pancreatic tumours. We demonstrated the efficacy of PET imaging with an 18 F-labelled lactose derivative, [ 18 F]FEDL, that targets HIP/PAP, a biomarker that is overexpressed in the peritumoural pancreas. We developed another analogue, 1-[ 18 F]fluoroethyl lactose ([ 18 F]FEL), which is simpler to synthesise, for the same application. We conducted a preliminary evaluation of the new probe and its efficacy in detecting orthotopic pancreatic carcinoma xenografts in mice. Methods Xenografts were developed in nude mice by injecting L3.6pl/GL + pancreatic carcinoma cells into the pancreas of each mouse. Tumour growth was monitored by bioluminescence imaging (BLI); accuracy of BLI tumour size estimates was verified by MRI in two representative mice. When the tumour size reached approximately 2–3 mm, the animals were injected with [ 18 F]FEL (3.7 MBq) and underwent static PET/CT scans. Blood samples were collected at 2, 5, 10, 20 and 60 min after [ 18 F]FEL injection to track blood clearance. Following imaging, animals were sacrificed and their organs and tumours/pancreatic tissue were collected and counted on a gamma counter. Pancreas, including tumour, was frozen, sliced and used for autoradiography and immunohistochemical analysis of HIP/PAP expression. Results Tumour growth was rapid, as observed by BLI and MRI. Blood clearance of [ 18 F]FEL was bi-exponential, with half-lives of approximately 3.5 min and 40 min. Mean accumulation of [ 18 F]FEL in the peritumoural pancreatic tissue was 1.29 ± 0.295 %ID/g, and that in the normal pancreas of control animals was 0.090 ± 0.101 %ID/g. [ 18 F]FEL was cleared predominantly by the kidneys. Comparative analysis of autoradiographic images and immunostaining results demonstrated a correlation between [ 18 F]FEL binding and HIP/PAP expression. Conclusion [ 18 F]FEL may be useful for non-invasive imaging of early-stage pancreatic tumours by PET. The results warrant further studies. [ABSTRACT FROM AUTHOR]

We live in an unprecedented time in oncology. We have accumulated samples and cases in cohorts larger and more complex than ever before. New technologies are available for quantifying solid or liquid samples at the molecular level. At the same time, we are now equipped with the computational power necessary to handle this enormous amount of quantitative data. Computational models are widely used helping us to substantiate and interpret data. Under the label of systems and precision medicine, we are putting all these developments together to improve and personalize the therapy of cancer. In this review, we use melanoma as a paradigm to present the successful application of these technologies but also to discuss possible future developments in patient care linked to them. Melanoma is a paradigmatic case for disruptive improvements in therapies, with a considerable number of metastatic melanoma patients benefiting from novel therapies. Nevertheless, a large proportion of patients does not respond to therapy or suffers from adverse events. Melanoma is an ideal case study to deploy advanced technologies not only due to the medical need but also to some intrinsic features of melanoma as a disease and the skin as an organ. From the perspective of data acquisition, the skin is the ideal organ due to its accessibility and suitability for many kinds of advanced imaging techniques. We put special emphasis on the necessity of computational strategies to integrate multiple sources of quantitative data describing the tumour at different scales and levels., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Purpose: The present work was aimed at the formulation and evaluation of freeze-dried kits of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-peptides for the preparation of Ga-labelled peptides for PET imaging of neuroendocrine tumours. The GaCl was obtained from the locally produced nanoceria-PAN, composite-sorbent-based Ge/Ga generator. Procedures: Single vial kits of somatostatin analogues DOTA-[Tyr]-octreotide (DOTA-TOC), DOTA-[NaI]-octreotide (DOTA-NOC) and DOTA-Tyr-Thre-octreotide (DOTA-TATE) were formulated. Optimization of radiolabelling with Ga from the in-house generator, characterization, long term evaluation of stability of kits and bioevaluation studies in animals was carried out. Results: DOTA-TOC, DOTA-NOC and DOTA-TATE kits could be successfully formulated. Consistently high radiochemical yields (>95 %) were obtained on radiolabelling with Ga. The radiolabelled peptides exhibited excellent in vitro stability. Biodistribution studies in normal non-tumour bearing Swiss mice revealed fast clearance of activity via renal route as reported for the respective peptides. Conclusion: Availability of ready to use DOTA-peptide kits in conjunction with Ge/Ga generators would pave way for the establishment of Ga radiopharmacy, a long-felt need of the nuclear medicine community. [ABSTRACT FROM AUTHOR]

The redox-active transition metal copper is an essential trace element for growth and development and serves as a structural or catalytic cofactor for many enzymes in a range of physiological processes. Mammalian copper homeostasis is tightly regulated, and an imbalance in copper metabolism is implicated in various pathological disorders. Radioactive copper isotopes, in particular 64Cu ( t1/2 = 12.7 h) and 67Cu ( t1/2 = 62.01 h), have made important contributions to the understanding of copper metabolism in health and disease. This review gives a brief account of how radiolabelled copper(II) salts and bioreductive copper complexes have been used to trace copper uptake, transport and efflux in vitro and in vivo. Recently, positron emission tomography (PET) has emerged as a noninvasive tool to image copper metabolism in living subjects and 64Cu-PET is investigated for the study of copper-related neurological disorders, genetic diseases and cancer. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Purpose: We prospectively evaluated whether a strategy using point spread function (PSF) reconstruction for both diagnostic and quantitative analysis in non-small cell lung cancer (NSCLC) patients meets the European Association of Nuclear Medicine (EANM) guidelines for harmonization of quantitative values. Methods: The NEMA NU-2 phantom was used to determine the optimal filter to apply to PSF-reconstructed images in order to obtain recovery coefficients (RCs) fulfilling the EANM guidelines for tumour positron emission tomography (PET) imaging (PSF). PET data of 52 consecutive NSCLC patients were reconstructed with unfiltered PSF reconstruction (PSF), PSF and with a conventional ordered subset expectation maximization (OSEM) algorithm known to meet EANM guidelines. To mimic a situation in which a patient would undergo pre- and post-therapy PET scans on different generation PET systems, standardized uptake values (SUVs) for OSEM reconstruction were compared to SUVs for PSF and PSF reconstruction. Results: Overall, in 195 lesions, Bland-Altman analysis demonstrated that the mean ratio between PSF and OSEM data was 1.03 [95 % confidence interval (CI) 0.94-1.12] and 1.02 (95 % CI 0.90-1.14) for SUV and SUV, respectively. No difference was noticed when analysing lesions based on their size and location or on patient body habitus and image noise. Ten patients (84 lesions) underwent two PET scans for response monitoring. Using the European Organization for Research and Treatment of Cancer (EORTC) criteria, there was an almost perfect agreement between OSEM/OSEM (current standard) and OSEM/PSF or PSF/OSEM with kappa values of 0.95 (95 % CI 0.91-1.00) and 0.99 (95 % CI 0.96-1.00), respectively. The use of PSF either for pre- or post-treatment (i.e. OSEM/PSF or PSF/OSEM) showed considerably less agreement with kappa values of 0.75 (95 % CI 0.67-0.83) and 0.86 (95 % CI 0.78-0.94), respectively. Conclusion: Protocol-optimized images and compliance with EANM guidelines allowed for a reliable pre- and post-therapy evaluation when using different generation PET systems. These data obtained in NSCLC patients could be extrapolated to other solid tumours. [ABSTRACT FROM AUTHOR]

Dynamic contrast enhanced magnetic resonance imaging ( DCE- MRI) is a functional imaging technique that assesses the physiology of tumour tissue by exploiting abnormal tumour microvasculature. Advances made through DCE- MRI include improvement in the diagnosis of cancer, optimization of treatment choices, assessment of treatment efficacy and non-invasive identification of prognostic information. DCE- MRI enables quantitative assessment of tissue vessel density, integrity, and permeability, and this information can be applied to study of angiogenesis, hypoxia and the evaluation of various biomarkers. Reproducibility of DCE- MRI results is important in determining the significance of observed changes in the parameters. As improvements are made towards the utility of DCE- MRI and interpreting biologic associations, the technique will be applied more frequently in the study of cancer in animals. Given the importance of tumour perfusion with respect to tumour oxygenation and drug delivery, the use of DCE- MRI is a convenient and powerful way to gain basic information about a tumour. [ABSTRACT FROM AUTHOR]

C-terminally amidated gastrins act at cholecystokinin-2 receptors (CCK2R), which are normally expressed by gastric parietal and enterochromaffin-like (ECL) cells and smooth muscle; there is also extensive expression in the CNS where the main endogenous ligand is cholecystokinin. A variety of neoplasms express CCK2R, or splice variants, including neuroendocrine, pancreatic, medullary thyroid and lung cancers. Other products of the gastrin gene (progastrin, the Gly-gastrins) may stimulate cell proliferation but are not CCK2R ligands. Depending on the cell type, stimulation of CCK2R evokes secretion, increases proliferation and cell migration, inhibits apoptosis, and controls the expression of various genes. These effects are mediated by increased intracellular calcium and activation of protein kinase C, MAPkinase and other protein kinase cascades. There has been recent progress in developing CCK2R ligands that can be used for imaging tumours expressing the receptor. New antagonists have also been developed, and there is scope for using these for suppression of gastric acid and for treatment of neuroendocrine and other CCK2R-expressing tumours. [ABSTRACT FROM AUTHOR]

The aim of this document is to provide general information about mIBG scintigraphy in cancer patients. The guidelines describe the mIBG scintigraphy protocol currently used in clinical routine, but do not include all existing procedures for neuroendocrine tumours. The guidelines should therefore not be taken as exclusive of other nuclear medicine modalities that can be used to obtain comparable results. It is important to remember that the resources and facilities available for patient care may vary from one country to another and from one medical institution to another. The present guidelines have been prepared for nuclear medicine physicians and intend to offer assistance in optimizing the diagnostic information that can currently be obtained from mIBG scintigraphy. The corresponding guidelines of the Society of Nuclear Medicine (SNM) and the Dosimetry, Therapy and Paediatric Committee of the EANM have been taken into consideration, and partially integrated into this text. The same has been done with the most relevant literature on this topic, and the final result has been discussed within a group of distinguished experts. [ABSTRACT FROM AUTHOR]

The aim of these guidelines is to assist nuclear medicine physicians in recommending, performing, reporting and interpreting the results of somatostatin (SST) receptor PET/CT imaging using Ga-DOTA-conjugated peptides, analogues of octreotide, that bind to SST receptors. This imaging modality should not be regarded as the only approach to visualizing tumours expressing SST receptors or as excluding other imaging modalities useful for obtaining comparable results. The corresponding guidelines of In-pentetreotide scintigraphy imaging have been considered and partially integrated with this text. The same has been done with the relevant and recent literature in this field and the final result has been discussed by distinguished experts. [ABSTRACT FROM AUTHOR]

This document provides general information about somatostatin receptor scintigraphy with 111In-pentetreotide. This guideline should not be regarded as the only approach to visualise tumours expressing somatostatin receptors or as exclusive of other nuclear medicine procedures useful to obtain comparable results. The aim of this guideline is to assist nuclear medicine physicians in recommending, performing, reporting and interpreting the results of 111In-pentetreotide scintigraphy. [ABSTRACT FROM AUTHOR]

In this review we discuss the development of paramagnetic liposomes incorporating MRI contrast agents and show how these are utilized in cellular imaging in vitro. Bi-functional, bi-modal imaging paramagnetic liposome systems are also described. Next we discuss the upgrading of paramagnetic liposomes into bi-modal imaging neutral nanoparticles for in vivo imaging applications. We discuss the development of such systems and show how paramagnetic liposomes and imaging nanoparticles could be developed as platforms for future multi-functional, multi-modal imaging theranostic nanodevices tailor-made for the combined imaging of early stage disease pathology and functional drug delivery. [ABSTRACT FROM AUTHOR]

Background: The type I insulin-like growth factor receptor (IGF1R) is a transmembrane tyrosine kinase involved in cancer proliferation, survival, and metastasis.Methods: In this study, we used two different fluorescent technologies (small-molecule fluorophores and quantum dot (QD) nanoparticles) to detect receptor expression and its downregulation by antibodies in vivo.Results: After conjugation with AVE-1642, a humanised anti-IGF1R monoclonal antibody, both QDs (705 nm) or Alexa 680 (small-molecule fluorophore) detected expression and downregulation of IGF1R in vitro. To examine their utility in vivo, either AVE-1642 conjugates were intravenously delivered to mice bearing xenograft tumours of mouse embryo fibroblasts expressing human IGF1R or MCF-7 human breast cancer cells. Quantum dot fluorescence was mainly localised to the reticuloendothelial system in several organs and engulfed by macrophages, with only very small amount of QDs detected in the xenograft tumours. Depletion of macrophages by clodronate liposomes did not alter the nonspecific uptake of QDs. In contrast, AVE-1642-conjugated Alexa 680 solely targeted to xenograft tumour and was able to detect IGF1R downregulation, with little nonspecific targeting to other tissues or organs in mice.Conclusion: Taken together, our data suggest that small-molecule fluorophores, not QDs, are suitable to detect the expression and downregulation of IGF1R in vivo. [ABSTRACT FROM AUTHOR]

In this study, we investigated the effectiveness of positron emission tomography (PET) with 11C-acetate (AC) for evaluation of renal cell carcinoma. Enrolled in the study were 20 patients with suspected renal tumour, one of whom had three renal lesions. In all, 22 renal lesions were evaluated. Following administration of 350 MBq (10 mCi) of AC, whole-body PET images were obtained. Based on these PET findings, kidney lesions were scored as positive or negative. The PET results were correlated with the CT findings and histological diagnosis after surgery. In 18 patients, 20 tumours were diagnosed as renal cell carcinoma. Lesions in the remaining two patients were diagnosed as complicated cyst without malignant tissue. Of the 20 renal cell carcinomas. 14 (70%) showed positive AC PET findings; 6 were negative. The two patients with complicated cyst had negative AC PET findings. Of the 20 renal cell carcinomas, 19 were clear-cell carcinoma and 1 was a papillary cell carcinoma. This papillary cell carcinoma showed high AC uptake. AC demonstrates marked uptake in renal cell carcinoma. These preliminary data show that AC is a possible PET tracer for detection of renal cancer. [ABSTRACT FROM AUTHOR]

Neurotensin (NT) and its high affinity receptor (NTR1) are involved in several neoplastic processes. Thus, NT-based radiopharmaceuticals are potential tracers for targeted diagnosis and therapy of NTR-positive tumours. A new analogue based on NT(8–13), NT-XIX, with the three enzymatic cleavage sites stabilised, was synthesised and tested. The synthesis was performed by Boc strategy. Labelling with 99mTc/188Re was performed using the tricarbonyl technique. Metabolic stability was tested in vitro and in vivo . NT-XIX was further characterised in vitro in HT-29 cells and in vivo in nude mice with HT-29 xenografts. NT-XIX showed much longer half-lives than non-stabilised analogues. Binding to NTR1 was highly specific, although the affinity was lower than that of natural NT. Bound activity rapidly internalised into HT-29 cells and 50% remained trapped after 24 h. In the time-course biodistribution, the highest uptake was found in the tumour at all p.i. times. In vivo uptake was specific, and accumulation of activity in the kidneys was low. Radioactivity clearance from healthy organs was faster than that from the tumour, resulting in improved tumour-to-tissue ratios and good SPECT/CT imaging. Treatment with 188Re-NT-XIX (30 MBq, in three or four fractions) decreased tumour growth by 50% after 3 weeks. The high in vivo stability and the favourable in vivo behaviour makes NT-XIX an excellent candidate for the imaging and therapy of NTR1-positive tumours. [ABSTRACT FROM AUTHOR]

In vivo bioluminescence imaging (BLI) is a promising technique for non-invasive tumour imaging. d-luciferin can be administrated intraperitonealy or intravenously. This will influence its availability and, therefore, the bioluminescent signal. The aim of this study is to compare the repeatability of BLI measurement after IV versus IP administration of d-luciferin and assess the correlation between photon emission and histological cell count both in vitro and in vivo. Fluc-positive R1M cells were subcutaneously inoculated in nu/nu mice. Dynamic BLI was performed after IV or IP administration of d-luciferin. Maximal photon emission (PEmax) was calculated. For repeatability assessment, every acquisition was repeated after 4 h and analysed using Bland–Altman method. A second group of animals was serially imaged, alternating IV and IP administration up to 21 days. When mice were killed, PEmax after IV administration was correlated with histological cell number. The coefficients of repeatability were 80.2% (IV) versus 95.0% (IP). Time-to-peak is shorter, and its variance lower for IV ( p < 0.0001). PEmax was 5.6 times higher for IV. A trend was observed towards lower photon emission per cell in larger tumours. IV administration offers better repeatability and better sensitivity when compared to IP. In larger tumours, multiple factors may contribute to underestimation of tumour burden. It might, therefore, be beneficial to test novel therapeutics on small tumours to enable an accurate evaluation of tumour burden. [ABSTRACT FROM AUTHOR]

The molecular imaging of tumour neoangiogenesis currently represents a major field of research for the diagnostic and treatment strategy of solid tumours. Endothelial cells from tumour neovessels overexpress the αvβ3 integrin, which selectively binds to Arg-Gly-Asp (RGD)-containing peptides. We evaluated the potential of the novel radiotracer 99mTc-RAFT-RGD for the non-invasive molecular imaging of αvβ3 integrin expression in mice models of tumour development. 99mTc-RAFT-RGD, 99mTc-cRGD (specific control) and 99mTc-RAFT-RAD (non-specific control) were injected intravenously to mice bearing B16F0 or TS/A-pc tumours. In vivo whole-body tomographic imaging and post-mortem biodistribution studies were performed 60 min following tracer injection. Adjacent tumour slices were used to compare the localisation of neovessels from immunostaining and the pattern of 99mTc-RAFT-RGD uptake from autoradiographic ex vivo imaging. Biodistribution studies indicated that 99mTc-RAFT-RGD tumour uptake was significantly higher than that of 99mTc-RAFT-RAD in B16F0 (2.4±0.5 vs 1.0±0.1%ID/g, respectively) and in TS/A-pc tumours (2.7±0.8 vs 0.7±0.1%ID/g, respectively). Immunohistochemical and autoradiographic studies indicated that 99mTc-RAFT-RGD intratumoural uptake preferentially occurred in angiogenic areas. Tomographic imaging allowed tumour visualisation following injection of 99mTc-RAFT-RGD and 99mTc-cRGD with similar tumour-to-contralateral muscle (T/CM) ratios in B16F0 and in TS/A-pc tumours whereas 99mTc-RAFT-RAD T/CM ratios did not allow tumour imaging. In accordance with the higher level of αvβ3 integrin expression on TS/A-pc tumours than on B16F0 tumours as determined from western blot and immunoprecipitation analyses, the 99mTc-RAFT-RGD T/CM ratio was significantly higher in TS/A-pc than in B16F0 tumours. 99mTc-RAFT-RGD allowed the in vivo imaging of αvβ3 integrin tumour expression. [ABSTRACT FROM AUTHOR]

The study investigated the feasibility of a positron-sensitive hand-held detector system for the intraoperative localisation of tumour deposits resulting from intravenous [18F]FDG administration. A total of 17 patients (12 receiving preoperative [18F]FDG PET imaging) with various histologically proven malignancies were included. Radioactivity from tumours and surrounding normal tissue was measured on average 3 h after administration of 36–110 MBq [18F]FDG and the tumour-to-background (T/B) ratio was calculated. In addition, phantom studies were performed to evaluate the spatial resolution and sensitivity of the probe. All known targeted tumour sites were identified by the positron probe. T/B ratios were generally high, with a mean T/B ratio of 6.6, allowing easy identification of most tumour sites. In one case of a hepatic metastasis, the T/B ratio of 1.34 was below expectations, since the preoperative [18F]FDG PET scan was positive. The probe was instrumental in the localisation of three additional tumour lesions (two lymph nodes, one anastomotic ring) that were not immediately apparent at surgery. Phantom studies revealed that [18F]FDG-containing gel (simulating tumour tissue), having 10 times more [18F]FDG than surrounding “normal” background gel, was clearly detectable in quantities as low as 15 mg. As measured in two cases, the absorbed radiation doses ranged from 2.5 to 8.6 μSv/h for the surgical team to 0.8 μSv/h for the aesthetician. [18F]FDG-accumulating tumour tissues can be localised with positron probes intraoperatively with a low radiation burden to the patient and medical personnel. The methodology holds promise for further clinical testing. [ABSTRACT FROM AUTHOR]