Targeted Radionuclide Therapy: An Evolution Toward Precision Cancer Treatment

Jadvar, Hossein

doi:10.2214/ajr.17.18264

Cited by 74 publications

(46 citation statements)

References 158 publications

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“…A rapidly developing area of clinical application is the use of PET for monitoring radionuclide therapy (54,55), especially for neuroendocrine tumors and prostate cancer. Total-body PET should be an ideal tool for longitudinally evaluating the results of these therapies in multiple metastases spread through the body.…”

Section: Clinical Carementioning

confidence: 99%

Total-Body PET: Maximizing Sensitivity to Create New Opportunities for Clinical Research and Patient Care

et al. 2017

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PET is widely considered the most sensitive technique available for noninvasively studying physiology, metabolism, and molecular pathways in the living human being. However, the utility of PET, being a photon-deficient modality, remains constrained by factors including low signal-to-noise ratio, long imaging times, and concerns about radiation dose. Two developments offer the potential to dramatically increase the effective sensitivity of PET. First by increasing the geometric coverage to encompass the entire body, sensitivity can be increased by a factor of about 40 for total-body imaging or a factor of about 4-5 for imaging a single organ such as the brain or heart. The world's first total-body PET/CT scanner is currently under construction to demonstrate how this step change in sensitivity affects the way PET is used both in clinical research and in patient care. Second, there is the future prospect of significant improvements in timing resolution that could lead to further effective sensitivity gains. When combined with total-body PET, this could produce overall sensitivity gains of more than 2 orders of magnitude compared with existing state-of-the-art systems. In this article, we discuss the benefits of increasing body coverage, describe our efforts to develop a first-generation total-body PET/CT scanner, discuss selected application areas for total-body PET, and project the impact of further improvements in time-of-flight PET.Key Words: instrumentation; molecular imaging; PET/CT; instrumentation; PET; total-body imaging J Nucl Med 2018; 59:3-12 DOI: 10.2967/jnumed.116.184028Al l nuclear medicine studies in humans are limited by the trade-offs between the number of detected decay events, imaging time, and absorbed dose. The number of detected events determines the signal-to-noise ratio (SNR) in the final image, but constraints on administered activity, as well as high random event rates and dead time that occur at high activities, currently prevent acquisition of high-SNR images in short times. This in turn limits the ability to perform high-resolution, dynamic imaging studies with tracer kinetic modeling, because short-time-frame datasets are always noisy. A further limitation is that although the tracer injection is systemic and radiotracer is present in the entire body, current imaging systems contain only a small portion of the body within the field of view (FOV). For applications in which the distribution of radiotracer in the entire body or multiple organ systems is of interest, this limitation leads to further inefficiencies and makes it difficult to acquire dynamic data from all the tissues of interest. If one takes whole-body PET scanning with 18 F-FDG as an example, the total efficiency with which pairs of coincidence photons that escape the body are detected is well under 1% even on today's best scanners. Simplistically, this number can be derived by considering that the average geometric sensitivity within the FOV of a typical clinical PET scanner is under 5% and that with an axial coverage of ...

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Section: Clinical Carementioning

confidence: 99%

Total-Body PET: Maximizing Sensitivity to Create New Opportunities for Clinical Research and Patient Care

et al. 2017

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“…The elimination of cancer cells from bone metastases is crucial for treatment efficacy, which requires precise and efficient delivery of antitumor therapeutics to bone metastases. Clinically, bone-targeting radiopharmaceuticals such as 153 Sm-ethylenediaminetetramethylenephosphonate and 89 Sr-chloride are widely applied β-emitters for bone palliation 11 . Currently, 223 Ra-dichloride is approved as a bone-seeking calcium-mimetic radiopharmaceutical for treatment of metastatic castration-resistant prostate cancer patients by emitting α-particles 12 .…”

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confidence: 99%

Targeting of radioactive platinum-bisphosphonate anticancer drugs to bone of high metabolic activity

Nadar

Farbod

Schilden

et al. 2020

Sci Rep

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platinum-based chemotherapeutics exhibit excellent antitumor properties. However, these drugs cause severe side effects including toxicity, drug resistance, and lack of tumor selectivity. Tumor-targeted drug delivery has demonstrated great potential to overcome these drawbacks. Herein, we aimed to design radioactive bisphosphonate-functionalized platinum (195m Pt-BP) complexes to confirm preferential accumulation of these pt-based drugs in metabolically active bone. In vitro nMR studies revealed that release of pt from pt Bp complexes increased with decreasing pH. Upon systemic administration to mice, Pt-BP exhibited a 4.5-fold higher affinity to bone compared to platinum complexes lacking the bone-seeking bisphosphonate moiety. these pt-Bp complexes formed less pt-DnA adducts compared to bisphosphonate-free platinum complexes, indicating that in vivo release of pt from pt-Bp complexes proceeded relatively slow. Subsequently, radioactive 195m pt-Bp complexes were synthesized using 195m pt(no 3) 2 (en) as precursor and injected intravenously into mice. Specific accumulation of 195m pt-Bp was observed at skeletal sites with high metabolic activity using micro-Spect/ct imaging. Furthermore, laser ablation-ICP-MS imaging of proximal tibia sections confirmed that 195m pt Bp colocalized with calcium in the trabeculae of mice tibia. Most types of tumors, i.e. breast, prostate, lung, kidney, and thyroid, metastasize to bone since its physiological environment facilitates the formation and growth of cancer cells 1,2. These metastases affect healthy bone, which then become the primary cause of mortality 3. Distant metastases are the leading cause of death for both breast and prostate cancer patients, with 65-75% and 90% of these patients developing bone metastases in advanced stages, respectively 4,5. Bone metastases are often associated with accelerated bone resorption leading to complications such as skeletal-related events (SREs), bone pain or hypercalcemia 6,7. Unfortunately, current treatments for bone metastases are limited. Bisphosphonates (BP) and denosumab are most commonly used for palliative treatment to prevent or limit SREs 8. Although such treatments inhibit osteoclast activity and prevent the progression of metastases, they do not kill cancer cells effectively and do not improve the quality of life of patients substantially 9. Consequently, the development of effective therapies to treat bone metastases remains a major clinical challenge.

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“…The limited availability of representative clinical data on radioligand therapy poses a challenge [12], potentially contributing to significant disparities in availability across Europe [10,24]. The absence of clear and consistent understanding of what constitutes a response to radioligand therapy is an important challenge [5,12,24,25]. Analysis of existing clinical trial data may be hindered by the heterogeneity of patient groups with advanced cancer and the retrospective nature of the data [5,12].…”

Section: Lack Of Data and Researchmentioning

confidence: 99%

Realising the potential of radioligand therapy: policy solutions for the barriers to implementation across Europe

Merkel

Whicher

Bomanji³

et al. 2020

Eur J Nucl Med Mol Imaging

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BackgroundThe use of targeted radiation with radioisotopes has been applied for decades in thyroid cancer. However, the use of radioligand therapy-also referred to as peptide-receptor radionuclide therapy (PRRT), systemic radiation therapy, targeted radionuclide therapy (TRT), targeted radiotherapy or molecular radiotherapy-is now gaining ground more broadly in oncology. Therapies have been approved for a small number of cancers where few treatment options exist, such as midgut neuroendocrine tumours and metastatic castration-resistant prostate cancer (mCRPC) [1, 2], and they have been shown to improve progression-free survival and quality of life for many patients [3][4][5][6][7]. The approach is also being explored in other cancer and non-cancer conditions.Nuclear medicine has, traditionally, sat somewhat on the sidelines of cancer care; however, the evolving oncology landscape suggests its role will grow, with broader applications in both diagnostics and therapy [8]. Nuclear medicine specialists will need to be fully integrated into multidisciplinary cancer care teams, and appropriate resourcing to deliver radioligand therapy-in terms of hospital infrastructure and workforce, as well as nuclear waste facilities-will need to be taken into account in future cancer plans and care pathways.Over the course of 2019, we conducted desk research and semi-structured expert interviews to explore potential barriers to achieving this integration in practice, drawing on insights from five different countries-Germany, Italy, Poland, Spain and the United Kingdom. The resulting document, 'Radioligand therapy: realising the potential of targeted cancer care', [9] was launched at the European Parliament in January 2020 along with an accompanying video explaining radioligand therapy for a lay audience. This report is an important reminder to the fields of nuclear medicine and oncology of the factors necessary to ensure advances in nuclear medicine reach patients in future models of cancer care.What are the potential barriers to integration of radioligand therapy into cancer care?Healthcare systems are often inadequately prepared for greater utilisation and integration of radioligand therapy. The report identified six key barriers to the greater integration of radioligand therapy into cancer care: low awareness and understanding; limited professional capacity, training and workforce planning; unclear models of care; inadequate physical capacity and resourcing in hospitals; evolving legislation, regulation and policy; and lack of data and research [9].

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Targeted Radionuclide Therapy: An Evolution Toward Precision Cancer Treatment

Cited by 74 publications

References 158 publications

Total-Body PET: Maximizing Sensitivity to Create New Opportunities for Clinical Research and Patient Care

Total-Body PET: Maximizing Sensitivity to Create New Opportunities for Clinical Research and Patient Care

Targeting of radioactive platinum-bisphosphonate anticancer drugs to bone of high metabolic activity

Realising the potential of radioligand therapy: policy solutions for the barriers to implementation across Europe

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