In Vivo Imaging in Pharmaceutical Development and Its Impact on the 3Rs

Campbell, Barry; Trotter, Dinko González; Hines, Catherine D. G.; Patel, Manishkumar; Zhang, Weisheng; Evelhoch, Jeffrey L.

doi:10.1093/ilar/ilw019

Cited by 20 publications

(16 citation statements)

References 55 publications

(54 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…At least two obstacles underlying this observation can be noted. First, regulatory hurdles and lack of funding to develop a full GMP-grade product dossier for FDA and EMA approval impede the translation of novel tracers [164–167]. Second, both regulatory bodies and oncological community still adhere to anatomical imaging biomarkers such as CT to evaluate tumour size as surrogate endpoint for efficacy.…”

Section: Discussion and Future Perspectivesmentioning

confidence: 99%

Imaging of T-cells and their responses during anti-cancer immunotherapy

Krekorian¹,

Fruhwirth²,

Srinivas³

et al. 2019

Theranostics

View full text Add to dashboard Cite

Immunotherapy has proven to be an effective approach in a growing number of cancers. Despite durable clinical responses achieved with antibodies targeting immune checkpoint molecules, many patients do not respond. The common denominator for immunotherapies that have successfully been introduced in the clinic is their potential to induce or enhance infiltration of cytotoxic T-cells into the tumour. However, in clinical research the molecules, cells and processes involved in effective responses during immunotherapy remain largely obscure. Therefore, in vivo imaging technologies that interrogate T-cell responses in patients represent a powerful tool to boost further development of immunotherapy. This review comprises a comprehensive analysis of the in vivo imaging technologies that allow the characterisation of T-cell responses induced by anti-cancer immunotherapy, with emphasis on technologies that are clinically available or have high translational potential. Throughout we discuss their respective strengths and weaknesses, providing arguments for selecting the optimal imaging options for future research and patient management.

show abstract

Section: Discussion and Future Perspectivesmentioning

confidence: 99%

Imaging of T-cells and their responses during anti-cancer immunotherapy

Krekorian¹,

Fruhwirth²,

Srinivas³

et al. 2019

Theranostics

View full text Add to dashboard Cite

show abstract

“…In the past decades, special focus has been placed on minimising animal use and suffering. In particular, longitudinal in vivo imaging has been proven to be a reliable method for response evaluation in mice with lung cancer [4,5,18,23,26,27]. Dedicated small animal CT and MRI scanners were designed for this purpose, but their availability is limited due to relatively high acquisition and maintenance costs.…”

Section: Discussionmentioning

confidence: 99%

“…Dedicated small animal CT and MRI scanners were designed for this purpose, but their availability is limited due to relatively high acquisition and maintenance costs. As clinical scanners are widely available, their utilisation in place of histology-based methods could strongly contribute to animal welfare and reduce the number of animals used in preclinical studies [4].…”

Section: Discussionmentioning

confidence: 99%

“…Unlike histology-based methods, which require surgery or mice sacrifice, in vivo imaging allows for non-invasive evaluation of therapy response and thereby permits a reduction of animal numbers compared to studies relying on histology as sole method for response evaluation [3,4]. Most preclinical studies use micro-computed tomography (micro-CT) or dedicated small animal magnetic resonance (micro-MRI) scanners to visualise and quantify lung tumours in mice, because both modalities offer high resolution and good correlation with histopathological results [5,6].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Monitoring treatment effects in lung cancer-bearing mice: clinical CT and clinical MRI compared to micro-CT

et al. 2020

View full text Add to dashboard Cite

Background Compared to histology-based methods, imaging can reduce animal usage in preclinical studies. However, availability of dedicated scanners is limited. We evaluated clinical computed tomography (CT) and magnetic resonance imaging (MRI) in comparison to dedicated CT (micro-CT) for assessing therapy effects in lung cancer-bearing mice. Methods Animals received cisplatin (n = 10), sham (n = 12), or no treatment (n = 9). All were examined via micro-CT, CT, and MRI before and after treatment. Semiautomated tumour burden (TB) calculation was performed. The Bland-Altman, receiver operating characteristic (ROC), and Spearman statistics were used. Results All modalities always allowed localising and measuring TB. At all modalities, mice treated with cisplatin showed a TB reduction (p ≤ 0.012) while sham-treated and untreated individuals presented tumour growth (p < 0.001). Mean relative difference (limits of agreement) between TB on micro-CT and clinical scanners was 24.7% (21.7–27.7%) for CT and 2.9% (−4.0–9.8%) for MRI. Relative TB changes before/after treatment were not different between micro-CT and CT (p = 0.074) or MRI (p = 0.241). Mice with cisplatin treatment were discriminated from those with sham or no treatment at all modalities (p ≤ 0.001). Using micro-CT as reference standard, ROC areas under the curves were 0.988–1.000 for CT and 0.946–0.957 for MRI. TB changes were highly correlated across modalities (r ≥ 0.900, p < 0.001). Conclusions Clinical CT and MRI are suitable for treatment response evaluation in lung cancer-bearing mice. When dedicated scanners are unavailable, they should be preferred to improve animal welfare.

show abstract

“… 548 Furthermore, these very same radiotracers can be used in animal disease models, enabling longitudinal studies and reducing the number of animals required. 549 - 551 …”

Section: Part Ii: Pipeline Development To Gain Novel Diagnostics and Therapeuticsmentioning

confidence: 99%

Strategies to gain novel Alzheimer’s disease diagnostics and therapeutics using modulators of ABCA transporters

Pahnke

Bascuñana

Brackhan

et al. 2021

Free Neuropathology

View full text Add to dashboard Cite

Adenosine-triphosphate-(ATP)-binding cassette (ABC) transport proteins are ubiquitously present membrane-bound efflux pumps that distribute endo- and xenobiotics across intra- and intercellular barriers. Discovered over 40 years ago, ABC transporters have been identified as key players in various human diseases, such as multidrug-resistant cancer and atherosclerosis, but also neurodegenerative diseases, such as Alzheimer’s disease (AD). Most prominent and well-studied are ABCB1, ABCC1, and ABCG2, not only due to their contribution to the multidrug resistance (MDR) phenotype in cancer, but also due to their contribution to AD. However, our understanding of other ABC transporters is limited, and most of the 49 human ABC transporters have been largely neglected as potential targets for novel small-molecule drugs. This is especially true for the ABCA subfamily, which contains several members known to play a role in AD initiation and progression. This review provides up-to-date information on the proposed functional background and pathological role of ABCA transporters in AD. We also provide an overview of small-molecules shown to interact with ABCA transporters as well as potential in silico , in vitro , and in vivo methodologies to gain novel templates for the development of innovative ABC transporter-targeting diagnostics and therapeutics.

show abstract

In Vivo Imaging in Pharmaceutical Development and Its Impact on the 3Rs

Cited by 20 publications

References 55 publications

Imaging of T-cells and their responses during anti-cancer immunotherapy

Imaging of T-cells and their responses during anti-cancer immunotherapy

Monitoring treatment effects in lung cancer-bearing mice: clinical CT and clinical MRI compared to micro-CT

Strategies to gain novel Alzheimer’s disease diagnostics and therapeutics using modulators of ABCA transporters

Contact Info

Product

Resources

About