Imaging with [89Zr]Zr-DFO-SC16.56 anti-DLL3 antibody in patients with high-grade neuroendocrine tumours of the lung and prostate: a phase 1/2, first-in-human trial.

BACKGROUND: Delta-like ligand 3 (DLL3) is aberrantly expressed on the surface of small-cell lung cancer (SCLC) and neuroendocrine prostate cancer cells. We assessed the safety and feasibility of the DLL3-targeted imaging tracer [89Zr]Zr-DFO-SC16.56 (composed of the anti-DLL3 antibody SC16.56 conjugated to p-SCN-Bn-deferoxamine [DFO] serving as a chelator for zirconium-89) in patients with neuroendocrine-derived cancer. METHODS: We conducted an open-label, first-in-human study of immunoPET-CT imaging with [89Zr]Zr-DFO-SC16.56. The study was done at Memorial Sloan Kettering Cancer Center, New York, NY, USA. Patients aged 18 years or older with a histologically verified neuroendocrine-derived malignancy and an Eastern Cooperative Oncology Group performance status of 0-2 were eligible. An initial cohort of patients with SCLC (cohort 1) received 37-74 MBq [89Zr]Zr-DFO-SC16.56 as a single intravenous infusion at a total mass dose of 2·5 mg and had serial PET-CT scans at 1 h, day 1, day 3, and day 7 post-injection. The primary outcomes of phase 1 of the study (cohort 1) were to estimate terminal clearance half-time, determine whole organ time-integrated activity coefficients, and assess the safety of [89Zr]Zr-DFO-SC16.56. An expansion cohort of additional patients (with SCLC, neuroendocrine prostate cancer, atypical carcinoid tumours, and non-small-cell lung cancer; cohort 2) received a single infusion of [89Zr]Zr-DFO-SC16.56 at the same activity and mass dose as in the initial cohort followed by a single PET-CT scan 3-6 days later. Retrospectively collected tumour biopsy samples were assessed for DLL3 by immunohistochemistry. The primary outcome of phase 2 of the study in cohort 2 was to determine the potential association between tumour uptake of the tracer and intratumoural DLL3 protein expression, as determined by immunohistochemistry. This study is ongoing and is registered with ClinicalTrials.gov, NCT04199741. FINDINGS: Between Feb 11, 2020, and Jan 30, 2023, 12 (67%) men and six (33%) women were enrolled, with a median age of 64 years (range 23-81). Cohort 1 included three patients and cohort 2 included 15 additional patients. Imaging of the three patients with SCLC in cohort 1 showed strong tumour-specific uptake of [89Zr]Zr-DFO-SC16.56 at day 3 and day 7 post-injection. Serum clearance was biphasic with an estimated terminal clearance half-time of 119 h (SD 31). The highest mean absorbed dose was observed in the liver (1·83 mGy/MBq [SD 0·36]), and the mean effective dose was 0·49 mSv/MBq (SD 0·10). In cohort 2, a single immunoPET-CT scan on day 3-6 post-administration could delineate DLL3-avid tumours in 12 (80%) of 15 patients. Tumoural uptake varied between and within patients, and across anatomical sites, with a wide range in maximum standardised uptake value (from 3·3 to 66·7). Tumour uptake by [89Zr]Zr-DFO-SC16.56 was congruent with DLL3 immunohistochemistry in 15 (94%) of 16 patients with evaluable tissue. Two patients with non-avid DLL3 SCLC and neuroendocrine prostate cancer by PET scan showed the lowest DLL3 expression by tumour immunohistochemistry. One (6%) of 18 patients had a grade 1 allergic reaction; no grade 2 or worse adverse events were noted in either cohort. INTERPRETATION: DLL3 PET-CT imaging of patients with neuroendocrine cancers is safe and feasible. These results show the potential utility of [89Zr]Zr-DFO-SC16.56 for non-invasive in-vivo detection of DLL3-expressing malignancies. FUNDING: National Institutes of Health, Prostate Cancer Foundation, and Scannell Foundation.

MIRD Pamphlet No. 29: MIRDy90-A 90Y Research Microsphere Dosimetry Tool.

90Y-microsphere radioembolization has become a well-established treatment option for liver malignancies and is one of the first U.S. Food and Drug Administration-approved unsealed radionuclide brachytherapy devices to incorporate dosimetry-based treatment planning. Several different mathematical models are used to calculate the patient-specific prescribed activity of 90Y, namely, body surface area (SIR-Spheres only), MIRD single compartment, and MIRD dual compartment (partition). Under the auspices of the MIRDsoft initiative to develop community dosimetry software and tools, the body surface area, MIRD single-compartment, MIRD dual-compartment, and MIRD multicompartment models have been integrated into a MIRDy90 software worksheet. The worksheet was built in MS Excel to estimate and compare prescribed activities calculated via these respective models. The MIRDy90 software was validated against available tools for calculating 90Y prescribed activity. The results of MIRDy90 calculations were compared with those obtained from vendor and community-developed tools, and the calculations agreed well. The MIRDy90 worksheet was developed to provide a vetted tool to better evaluate patient-specific prescribed activities calculated via different models, as well as model influences with respect to varying input parameters. MIRDy90 allows users to interact and visualize the results of various parameter combinations. Variables, equations, and calculations are described in the MIRDy90 documentation and articulated in the MIRDy90 worksheet. The worksheet is distributed as a free tool to build expertise within the medical physics community and create a vetted standard for model and variable management.

First-in-human imaging with [89Zr]Zr-DFO-SC16.56 anti-DLL3 antibody in patients with high-grade neuroendocrine tumors of the lung and prostate.

Background: Delta-like ligand 3 (DLL3) is aberrantly expressed on the cell surface in many neuroendocrine cancers including small cell lung cancer (SCLC) and neuroendocrine prostate cancer (NEPC). Several therapeutic agents targeting DLL3 are in active clinical development. Molecular imaging of DLL3 would enable non-invasive diagnostic assessment to inform the use of DLL3-targeting therapeutics or to assess disease treatment response. Methods: We conducted a first-in-human immuno-positron emission tomography (immunoPET) imaging study of [89Zr]Zr-DFO-SC16.56, composed of the anti-DLL3 antibody SC16.56 conjugated to desferrioxamine (DFO) and the positron-emitting radionuclide zirconium-89, in 18 patients with neuroendocrine cancers. An initial cohort of three patients received 1-2 mCi of [89Zr]Zr-DFO-SC16.56 at a total mass dose of 2·5 mg and underwent serial PET and computed tomography (CT) imaging over the course of one week. Radiotracer clearance, tumor uptake, and radiation dosimetry were estimated. An expansion cohort of 15 additional patients were imaged using the initial activity and mass dose. Retrospectively collected tumor biopsies were assessed for DLL3 by immunohistochemistry (IHC) (n = 16). Findings: Imaging of the initial 3 SCLC patients demonstrated strong tumor-specific uptake of [89Zr]Zr-DFO-SC16.56, with similar tumor: background ratios at days 3, 4, and 7 post-injection. Serum clearance was bi-phasic with an estimated terminal clearance half-time of 119 h. The sites of highest background tracer uptake were blood pool and liver. The normal tissue receiving the highest radiation dose was liver; 1·8 mGy/MBq, and the effective dose was 0.49 mSv/MBq. Tumoral uptake varied both between and within patients, and across anatomic sites, with a wide range in SUVmax (from 3·3 to 66·7). Tumor uptake by [89Zr]Zr-DFO-SC16.56 was associated with protein expression in all cases. Two non-avid DLL3 NEPC cases by PET scanning demonstrated the lowest DLL3 expression by tumor immunohistochemistry. Only one patient had a grade 1 allergic reaction, while no grade ≥2 adverse events noted. Interpretation: DLL3 PET imaging of patients with neuroendocrine cancers is safe and feasible. These results demonstrate the potential utility of [89Zr]Zr-DFO-SC16.56 for non-invasive in vivo detection of DLL3-expressing malignancies. Funding: Supported by NIH R01CA213448 (JTP), R35 CA263816 (CMR), U24 CA213274 (CMR), R35 CA232130 (JSL), and a Prostate Cancer Foundation TACTICAL Award (JSL), Scannell foundation. The Radiochemistry and Molecular Imaging Probes Core Facility is supported by NIH P30 CA08748.

Technical Note: Impact of impurities on Yttrium-90 glass microsphere activity quantitation.

BACKGROUND: Glass 90 Y microspheres are produced with known radionuclide impurities. These impurities are not independently monitored. Clinical instruments, including ionization chamber dose calibrators and positron emmission tomography (PET) cameras, can be much more sensitive in detecting signals from these impurities than to signals from 90 Y itself. PURPOSE: The "typical" levels of 90 Y impurities have been studied to assess their impact on dosimetry during internal implantation, and for the management of waste. However, unaccounted-for decay spectra of impurities can also have an impact on dose calibrator and PET readings. Thus, even what might be considered negligibly small impurity fractions, can in principle cause substantial overestimates of the amount of 90 Y activity present in a sample. To our knowledge, quantitative effects of radionuclide impurities in glass microspheres on activity measurements have not been documented in the field. As activity quantitation for dosimetry and its correlations with outcome becomes more prevalent, the effects of impurities on measurements may remain unaccounted for in dosimetry studies. METHODS: In this letter, we review theoretical and physical considerations that will result in asymmetric errors in quantitation from 90 Y impurities and estimate their typical and potential impact on clinical utilization. Among the common impurities 88 Y is of particular concern for its impact on 90 Y dose measurements because of its decay characteristics, along with other isotopes 91 Y and 46 Sc which can also impact measurements. RESULTS: The typical level of 88 Y impurities reported by the manufacturer should only cause small errors in dose calibrator and PET measurements made within the 12-day label-specified use-by period, up to 2.0% and 1.6%, respectively. However, the product specification max allowable impurity levels, specified by the manufacturer, leave open the potential for much greater bias from within the 12-day use-by period, potentially as high as 13.2% for dose calibrator measurements and 10.6% for PET from the 88 Y impurities. CONCLUSIONS: While typical levels of impurities appear to have acceptable impact on patient absorbed dose, it should be noted that they can have adverse effects on 90 Y radioactivity measurements. Furthermore, there is currently minimal independent verification and/or monitoring of impurity levels within the field.

Engineering CAR-T cells for radiohapten capture in imaging and radioimmunotherapy applications.

Rationale: The in vivo dynamics of CAR-T cells remain incompletely understood. Novel methods are urgently needed to longitudinally monitor transferred cells non-invasively for biodistribution, functionality, proliferation, and persistence in vivo and for improving their cytotoxic potency in case of treatment failure. Methods: Here we engineered CD19 CAR-T cells ("Thor"-cells) to express a membrane-bound scFv, huC825, that binds DOTA-haptens with picomolar affinity suitable for labeling with imaging or therapeutic radionuclides. We assess its versatile utility for serial tracking studies with PET and delivery of α-radionuclides to enhance anti-tumor killing efficacy in sub-optimal adoptive cell transfer in vivo using Thor-cells in lymphoma models. Results: We show that this reporter gene/probe platform enables repeated, sensitive, and specific assessment of the infused Thor-cells in the whole-body using PET/CT imaging with exceptionally high contrast. The uptake on PET correlates with the Thor-cells on a cellular and functional level. Furthermore, we report the ability of Thor-cells to accumulate cytotoxic alpha-emitting radionuclides preferentially at tumor sites, thus increasing therapeutic potency. Conclusion: Thor-cells are a new theranostic agent that may provide crucial information for better and safer clinical protocols of adoptive T cell therapies, as well as accelerated development strategies.

The risk index as a basis for risk/benefit analyses and protocol optimization in diagnostic nuclear imaging.

BACKGROUND: Potential risk associated with low-dose radiation exposures is often expressed using the effective dose (E) quantity. Other risk-related quantities have been proposed as alternatives. The recently introduced risk index (RI) shares similarities with E but expands the metric to incorporate medical imaging-appropriate risks factors including patient-specific size, age, and sex. PURPOSE: The aim of this work is to examine the RI metric for quantifying stochastic radiation risk and demonstrate its applications in nuclear imaging. The advantages in this improved metric may help the field progress toward stratified risk consideration in the course of patient management, improve efforts for procedure optimization, and support an evolution in the science of radiation risk assessment. METHODS: In this study we describe, implement, and calculate RI for various diagnostic nuclear imaging scenarios using reference biokinetics published in ICRP Publication 128 for commonly utilized radiopharmaceuticals. All absorbed dose, E and RI calculations were performed using the freely available MIRDcalc nuclear medicine dosimetry software; the organ specific risk parameters used in the software are also benchmarked in this text. The resulting RI and E values are compared and various trends in RI values identified. RESULTS: E and RI coefficients were calculated for 3016 use cases. Notably RI values vary depending on patient characteristics. Overall, across the population, global trends in RI values can be identified. In general, RI values were 2.15 times higher for females than males, due to higher risk coefficients and activities being distributed in smaller reference masses. The pediatric patients showed higher RIs than adults, as younger patients generally receive higher absorbed doses per administered activity, and are more radiosensitive, and have a longer projected lifespan at risk. A compendium of E and RI values is also provided in table format to serve as a reference for the community. CONCLUSIONS: RI is a rational quantity that could be used for justification, risk communication and protocol optimization in medical imaging. It has some advantages when compared to the long-utilized E value with respect to personalization, since accounts for patient size, age, sex, and natural incidence of cancer risk.

MIRD Pamphlet No. 28, Part 1: MIRDcalc-A Software Tool for Medical Internal Radiation Dosimetry.

Medical internal radiation dosimetry constitutes a fundamental aspect of diagnosis, treatment, optimization, and safety in nuclear medicine. The MIRD committee of the Society of Nuclear Medicine and Medical Imaging developed a new computational tool to support organ-level and suborgan tissue dosimetry (MIRDcalc, version 1). Based on a standard Excel spreadsheet platform, MIRDcalc provides enhanced capabilities to facilitate radiopharmaceutical internal dosimetry. This new computational tool implements the well-established MIRD schema for internal dosimetry. The spreadsheet incorporates a significantly enhanced database comprising details for 333 radionuclides, 12 phantom reference models (International Commission on Radiological Protection), 81 source regions, and 48 target regions, along with the ability to interpolate between models for patient-specific dosimetry. The software also includes sphere models of various composition for tumor dosimetry. MIRDcalc offers several noteworthy features for organ-level dosimetry, including modeling of blood source regions and dynamic source regions defined by user input, integration of tumor tissues, error propagation, quality control checks, batch processing, and report-preparation capabilities. MIRDcalc implements an immediate, easy-to-use single-screen interface. The MIRDcalc software is available for free download (www.mirdsoft.org) and has been approved by the Society of Nuclear Medicine and Molecular Imaging.

Yttrium-90 Activity Quantification in PET/CT-Guided Biopsy Specimens from Colorectal Hepatic Metastases Immediately after Transarterial Radioembolization Using Micro-CT and Autoradiography.

PURPOSE: To evaluate the yttrium-90 (90Y) activity distribution in biopsy tissue samples of the treated liver to quantify the dose with higher spatial resolution than positron emission tomography (PET) for accurate investigation of correlations with microscopic biological effects and to evaluate the radiation safety of this procedure. MATERIALS AND METHODS: Eighty-six core biopsy specimens were obtained from 18 colorectal liver metastases (CLMs) immediately after 90Y transarterial radioembolization (TARE) with either resin or glass microspheres using real-time 90Y PET/CT guidance in 17 patients. A high-resolution micro-computed tomography (micro-CT) scanner was used to image the microspheres in part of the specimens and allow quantification of 90Y activity directly or by calibrating autoradiography (ARG) images. The mean doses to the specimens were derived from the measured specimens' activity concentrations and from the PET/CT scan at the location of the biopsy needle tip for all cases. Staff exposures were monitored. RESULTS: The mean measured 90Y activity concentration in the CLM specimens at time of infusion was 2.4 ± 4.0 MBq/mL. The biopsies revealed higher activity heterogeneity than PET. Radiation exposure to the interventional radiologists during post-TARE biopsy procedures was minimal. CONCLUSIONS: Counting the microspheres and measuring the activity in biopsy specimens obtained after TARE are safe and feasible and can be used to determine the administered activity and its distribution in the treated and biopsied liver tissue with high spatial resolution. Complementing 90Y PET/CT imaging with this approach promises to yield more accurate direct correlation of histopathological changes and absorbed dose in the examined specimens.

Dosimetry in Radiopharmaceutical Therapy.

The application of radiopharmaceutical therapy for the treatment of certain diseases is well established, and the field is expanding. New therapeutic radiopharmaceuticals have been developed in recent years, and more are in the research pipeline. Concurrently, there is growing interest in the use of internal dosimetry as a means of personalizing, and potentially optimizing, such therapy for patients. Internal dosimetry is multifaceted, and the current state of the art is discussed in this continuing education article. Topics include the context of dosimetry, internal dosimetry methods, the advantages and disadvantages of incorporating dosimetry calculations in radiopharmaceutical therapy, a description of the workflow for implementing patient-specific dosimetry, and future prospects in the field.

Engineered Cells as a Test Platform for Radiohaptens in Pretargeted Imaging and Radioimmunotherapy Applications.

Pretargeted imaging and radioimmunotherapy approaches are designed to have superior targeting properties over directly targeted antibodies but impose more complex pharmacology, which hinders efforts to optimize the ligands prior to human applications. Human embryonic kidney 293T cells expressing the humanized single-chain variable fragment (scFv) C825 (huC825) with high-affinity for DOTA-haptens (293T-huC825) in a transmembrane-anchored format eliminated the requirement to use other pretargeting reagents and provided a simplified, accelerated assay of radiohapten capture while offering normalized cell surface expression of the molecular target of interest. Using binding assays, ex vivo biodistribution, and in vivo imaging, we demonstrated that radiohaptens based on benzyl-DOTA and a second generation "Proteus" DOTA-platform effectively and specifically engaged membrane-bound huC825, achieving favorable tumor-to-normal tissue uptake ratios in mice. Furthermore, [86Y]Y-DOTA-Bn predicted absorbed dose to critical organs with reasonable accuracy for both [177Lu]Lu-DOTA-Bn and [225Ac]Ac-Pr, which highlights the benefit of a dosimetry-based treatment approach.

Utility of Quantitative SPECT/CT Lymphoscintigraphy in Guiding Sentinel Lymph Node Biopsy in Head and Neck Melanoma.

PURPOSE: To investigate the use of advanced SPECT/CT quantification in guiding surgical selection of positive sentinel lymph nodes (SLNs) in head and neck melanoma. METHODS: We retrospectively reviewed data from patients with cutaneous head and neck melanoma who underwent lymphoscintigraphy with SPECT/CT prior to SLN biopsy (SLNB). Quantification of radiotracer uptake from SPECT/CT data was performed using in-house segmentation software. SLNs identified using SPECT/CT were compared to SLNs identified surgically using an intraoperative γ-probe. A radioactivity count threshold using SPECT/CT for detecting a positive SLN was calculated. RESULTS: One hundred and five patients were included. Median number of SLNs detected was 3/patient with SPECT/CT and 2/patient with intraoperative γ-probe. The hottest node identified by SPECT/CT and intraoperative γ-probe were identical in 85% of patients. All 20 histologically positive SLNs were identified by SPECT/CT and γ-probe. On follow-up, all nodal recurrences occurred at lymph node levels with the hottest node identified by SPECT/CT and either the hottest or second hottest node identified by γ-probe during SLNB. Using our data, a SPECT/CT radioactivity count threshold of 20% would eliminate the unnecessary removal of 11% of SPECT/CT identified nodes and 12% of intraoperatively detected nodes. CONCLUSION: Utilizing SPECT/CT quantification, we propose that a radioactivity count threshold can be developed to help guide the selective removal of lymph nodes in head and neck SLNB. Furthermore, the nodal level containing the hottest node identified by SPECT/CT quantification must be thoroughly investigated for SLNs and undergo careful follow-up and surveillance for recurrence.

Modern Radiopharmaceutical Dosimetry Should Include Robust Biodistribution Reporting.

Radiopharmaceutical dosimetry is an important area of nuclear medicine, and its advances have the potential to affect imaging and radiotherapy development and application protocols. Dosimetry is a computationally intensive, assumption-based process, and not all dosimetry is created equal. In this brief communication, we present biodistribution measurements as a valuable part of radiopharmaceutical dosimetry that is worthy of robust documentation. Biodistribution data are routinely collected in every dosimetry case and are integral to the subsequent dosimetry calculations. Standard documentation of these data may help us understand the value and limitations of our dosimetry estimates, identify errors, resolve discrepancies, and enable the reproducibility of results. We may also recognize that the modern digital landscape provides both opportunity and motivation to usher in the evolution of standards in our field. Ultimately, these steps may improve the current generally poor acceptance of dosimetry procedures by clinicians.

Endoscopic endonasal approach for mass resection of the pterygopalatine fossa.

OBJECTIVES: Access to the pterygopalatine fossa is very difficult due to its complex anatomy. Therefore, an open approach is traditionally used, but morbidity is unavoidable. To overcome this problem, an endoscopic endonasal approach was developed as a minimally invasive procedure. The surgical aim of the present study was to evaluate the utility of the endoscopic endonasal approach for the management of both benign and malignant tumors of the pterygopalatine fossa. METHOD: We report our experience with the endoscopic endonasal approach for the management of both benign and malignant tumors and summarize recent recommendations. A total of 13 patients underwent surgery via the endoscopic endonasal approach for pterygopalatine fossa masses from 2014 to 2016. This case group consisted of 12 benign tumors (10 juvenile nasopharyngeal angiofibromas and two schwannomas) and one malignant tumor. RESULTS: No recurrent tumor developed during the follow-up period. One residual tumor (juvenile nasopharyngeal angiofibroma) that remained in the cavernous sinus was stable. There were no significant complications. Typical sequelae included hypesthesia of the maxillary nerve, trismus, and dry eye syndrome. CONCLUSION: The low frequency of complications together with the high efficacy of resection support the use of the endoscopic endonasal approach as a feasible, safe, and beneficial technique for the management of masses in the pterygopalatine fossa.

[Endoscopic optical imaging methods in the diagnostics of the laryngeal cancer]. / Endoskopické optické zobrazovací metody v diagnostice nádoru hrtanu.

Endoscopic optical imaging methods for the detection of mucosal lesions in the ENT area have been developed for better and earlier detection of these changes. They can be divided into horizontal methods group - showing the surface of the mucous membrane (autofluorescence, photodynamic diagnosis, Narrow Band Imaging, magnifying and contact endoscopy) and vertical methods group - visualizing different layers of the mucosa (optical coherence tomography and confocal endomicroscopy). Some of them are routinely used in practice, others are used in experimental mode and their introduction into practice may be a matter of the near future. The authors present a comprehensive overview of available endoscopic optical imaging methods.

Validation of Software Gating: A Practical Technology for Respiratory Motion Correction in PET.

Purpose To assess the performance of hardware- and software-gating technologies in terms of qualitative and quantitative characteristics of respiratory motion in positron emission tomography (PET) imaging. Materials and Methods Between 2010 and 2013, 219 fluorine 18 fluorodeoxyglucose PET examinations were performed in 116 patients for assessment of pulmonary nodules. All patients provided informed consent in this institutional review board-approved study. Acquisitions were reconstructed as respiratory-gated images by using hardware-derived respiratory triggers and software-derived signal (via an automated postprocessing method). Asymmetry was evaluated in the joint distribution of reader preference, and linear mixed models were used to evaluate differences in outcomes according to gating type. Results In blind reviews of reconstructed gated images, software was selected as superior 16.9% of the time (111 of 657 image sets; 95% confidence interval [CI]: 14.0%, 19.8%), and hardware was selected as superior 6.2% of the time (41 of 657 image sets; 95% CI: 4.4%, 8.1%). Of the image sets, 76.9% (505 of 657; 95% CI: 73.6%, 80.1%) were judged as having indistinguishable motion quality. Quantitative analysis demonstrated that the two gating strategies exhibited similar performance, and the performance of both was significantly different from that of nongated images. The mean increase ± standard deviation in lesion maximum standardized uptake value was 42.2% ± 38.9 between nongated and software-gated images, and lesion full width at half maximum values decreased by 9.9% ± 9.6. Conclusion Compared with vendor-supplied respiratory-gating hardware methods, software gating performed favorably, both qualitatively and quantitatively. Fully automated gating is a feasible approach to motion correction of PET images. (©) RSNA, 2016 Online supplemental material is available for this article.

On transcending the impasse of respiratory motion correction applications in routine clinical imaging - a consideration of a fully automated data driven motion control framework.

Positron emission tomography (PET) is increasingly used for the detection, characterization, and follow-up of tumors located in the thorax. However, patient respiratory motion presents a unique limitation that hinders the application of high-resolution PET technology for this type of imaging. Efforts to transcend this limitation have been underway for more than a decade, yet PET remains for practical considerations a modality vulnerable to motion-induced image degradation. Respiratory motion control is not employed in routine clinical operations. In this article, we take an opportunity to highlight some of the recent advancements in data-driven motion control strategies and how they may form an underpinning for what we are presenting as a fully automated data-driven motion control framework. This framework represents an alternative direction for future endeavors in motion control and can conceptually connect individual focused studies with a strategy for addressing big picture challenges and goals.