ACR Appropriateness Criteria® Chronic Hand and Wrist Pain: 2023 Update.

Chronic hand and wrist pain is a common presenting complaint. The intricate anatomy results in a variety of pain generators-multiple bones, articular cartilage, intrinsic ligaments, triangular fibrocartilage complex, joint capsules and synovium, tendons and tendon sheaths, muscles, and nerves-in a compact space. The need for imaging and the choice of the appropriate imaging modality are best determined by the patient's presentation, physical examination, and the clinician's working differential diagnosis. Radiography is usually appropriate as the initial imaging study in the evaluation of chronic hand or wrist pain. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

Alliance for clinical trials in Oncology (Alliance) trial A022101/NRG-GI009: a pragmatic randomized phase III trial evaluating total ablative therapy for patients with limited metastatic colorectal cancer: evaluating radiation, ablation, and surgery (ERASur).

BACKGROUND: For patients with liver-confined metastatic colorectal cancer (mCRC), local therapy of isolated metastases has been associated with long-term progression-free and overall survival (OS). However, for patients with more advanced mCRC, including those with extrahepatic disease, the efficacy of local therapy is less clear although increasingly being used in clinical practice. Prospective studies to clarify the role of metastatic-directed therapies in patients with mCRC are needed. METHODS: The Evaluating Radiation, Ablation, and Surgery (ERASur) A022101/NRG-GI009 trial is a randomized, National Cancer Institute-sponsored phase III study evaluating if the addition of metastatic-directed therapy to standard of care systemic therapy improves OS in patients with newly diagnosed limited mCRC. Eligible patients require a pathologic diagnosis of CRC, have BRAF wild-type and microsatellite stable disease, and have 4 or fewer sites of metastatic disease identified on baseline imaging. Liver-only metastatic disease is not permitted. All metastatic lesions must be amenable to total ablative therapy (TAT), which includes surgical resection, microwave ablation, and/or stereotactic ablative body radiotherapy (SABR) with SABR required for at least one lesion. Patients without overt disease progression after 16-26 weeks of first-line systemic therapy will be randomized 1:1 to continuation of systemic therapy with or without TAT. The trial activated through the Cancer Trials Support Unit on January 10, 2023. The primary endpoint is OS. Secondary endpoints include event-free survival, adverse events profile, and time to local recurrence with exploratory biomarker analyses. This study requires a total of 346 evaluable patients to provide 80% power with a one-sided alpha of 0.05 to detect an improvement in OS from a median of 26 months in the control arm to 37 months in the experimental arm with a hazard ratio of 0.7. The trial uses a group sequential design with two interim analyses for futility. DISCUSSION: The ERASur trial employs a pragmatic interventional design to test the efficacy and safety of adding multimodality TAT to standard of care systemic therapy in patients with limited mCRC. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05673148, registered December 21, 2022.

Harnessing imaging tools to guide immunotherapy trials: summary from the National Cancer Institute Cancer Imaging Steering Committee workshop.

As the immuno-oncology field continues the rapid growth witnessed over the past decade, optimising patient outcomes requires an evolution in the current response-assessment guidelines for phase 2 and 3 immunotherapy clinical trials and clinical care. Additionally, investigational tools-including image analysis of standard-of-care scans (such as CT, magnetic resonance, and PET) with analytics, such as radiomics, functional magnetic resonance agents, and novel molecular-imaging PET agents-offer promising advancements for assessment of immunotherapy. To document current challenges and opportunities and identify next steps in immunotherapy diagnostic imaging, the National Cancer Institute Clinical Imaging Steering Committee convened a meeting with diverse representation among imaging experts and oncologists to generate a comprehensive review of the state of the field.

Alliance for Clinical Trials in Oncology (Alliance) trial A022101/NRG-GI009: A pragmatic randomized phase III trial evaluating total ablative therapy for patients with limited metastatic colorectal cancer: evaluating radiation, ablation, and surgery (ERASur).

Background: For patients with liver-confined metastatic colorectal cancer (mCRC), local therapy of isolated metastases has been associated with long-term progression-free and overall survival (OS). However, for patients with more advanced mCRC, including those with extrahepatic disease, the efficacy of local therapy is less clear although increasingly being used in clinical practice. Prospective studies to clarify the role of metastatic-directed therapies in patients with mCRC are needed. Methods: The Evaluating Radiation, Ablation, and Surgery (ERASur) A022101/NRG-GI009 trial is a randomized, National Cancer Institute-sponsored phase III study evaluating if the addition of metastatic-directed therapy to standard of care systemic therapy improves OS in patients with newly diagnosed limited mCRC. Eligible patients require a pathologic diagnosis of CRC, have BRAF wild-type and microsatellite stable disease, and have 4 or fewer sites of metastatic disease identified on baseline imaging. Liver-only metastatic disease is not permitted. All metastatic lesions must be amenable to total ablative therapy (TAT), which includes surgical resection, microwave ablation, and/or stereotactic ablative body radiotherapy (SABR) with SABR required for at least one lesion. Patients without overt disease progression after 16-26 weeks of first-line systemic therapy will be randomized 1:1 to continuation of systemic therapy with or without TAT. The trial activated through the Cancer Trials Support Unit on January 10, 2023. The primary endpoint is OS. Secondary endpoints include event-free survival, adverse events profile, and time to local recurrence with exploratory biomarker analyses. This study requires a total of 346 evaluable patients to provide 80% power with a one-sided alpha of 0.05 to detect an improvement in OS from a median of 26 months in the control arm to 37 months in the experimental arm with a hazard ratio of 0.7. The trial uses a group sequential design with two interim analyses for futility. Discussion: The ERASur trial employs a pragmatic interventional design to test the efficacy and safety of adding multimodality TAT to standard of care systemic therapy in patients with limited mCRC.

ACR Appropriateness Criteria® Hernia.

Abdominopelvic hernias are common clinical entities composed of a wide variety of congenital, traumatic, and iatrogenic etiologies. Any weakness in the body wall may result in hernia of cavity contents with concomitant risks of morbidity and mortality. Presentations may be specific, palpable body wall mass/bulge, or vague, nonspecific pain through bowel obstruction. This document focuses on initial imaging of the adult population with signs of symptoms prompting suspicion of abdominopelvic hernia. Imaging of the abdomen and pelvis to evaluate defects is essential for prompt diagnosis and treatment. Often CT and ultrasound are the first-line modalities to quickly evaluate the abdomen and pelvis, providing for accurate diagnoses and management of patients. MRI protocols may be useful as first-line imaging studies, especially in patients with orthopedic instrumentation. Although often performed, abdominal radiographs and fluorographic procedures may provide indirect evidence of hernias but are usually not indicated for initial diagnosis of hernia. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer-reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances in which peer-reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

ACR Appropriateness Criteria® Epigastric Pain.

Epigastric pain can have multiple etiologies including myocardial infarction, pancreatitis, acute aortic syndromes, gastroesophageal reflux disease, esophagitis, peptic ulcer disease, gastritis, duodenal ulcer disease, gastric cancer, and hiatal hernia. This document focuses on the scenarios in which epigastric pain is accompanied by symptoms such as heartburn, regurgitation, dysphagia, nausea, vomiting, and hematemesis, which raise suspicion for gastroesophageal reflux disease, esophagitis, peptic ulcer disease, gastritis, duodenal ulcer disease, gastric cancer, or hiatal hernia. Although endoscopy may be the test of choice for diagnosing these entities, patients may present with nonspecific or overlapping symptoms, necessitating the use of imaging prior to or instead of endoscopy. The utility of fluoroscopic imaging, CT, MRI, and FDG-PET for these indications are discussed. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Precision Nuclear Medicine: The Evolving Role of PET in Melanoma.

The clinical management of melanoma patients has been rapidly evolving with the introduction of new targeted immuno-oncology (IO) therapeutics. The current diagnostic paradigms for melanoma patients begins with the histopathologic confirmation of melanoma, initial staging of disease burden with imaging and surgical approaches, treatment monitoring during systemic cytotoxic chemotherapy or IO therapeutics, restaging after completion of adjuvant systemic, surgical, and/or external radiation therapy, and the detection of recurrent malignancy/metastatic disease following therapy. New and evolving imaging approaches with positron-emission tomography (PET) imaging technologies, imaging methodologies, image reconstruction, and image analytics will likely continue to improve tumor detection, tumor characterization, and diagnostic confidence, enabling novel precision nuclear medicine practices for managing melanoma patients. This review will examine current concepts and challenges with existing PET imaging diagnostics for melanoma patients and introduce exciting new opportunities for PET in the current era of IO therapeutics.

Prevalence of cancer and the benign call rate of afirma gene classifier in 18 F-Fluorodeoxyglucose positron emission tomography positive cytologically indeterminate thyroid nodules.

BACKGROUND: 18 F-Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) positive (PET+) cytologically indeterminate thyroid nodules (ITNs) have variable cancer risk in the literature. The benign call rate (BCR) of Afirma Gene Classifier (Gene Expression Classifier, GEC, or Genome Sequence Classifier, GSC) in (PET +) ITNs is unknown. METHODS: This is a retrospective study at our institution of all patients with (PET+) ITNs (Bethesda III/IV) from 1 January 2010 to 21 May 2019 who underwent Afirma testing and/or surgery or repeat FNA with benign cytology. RESULTS: Forty-five (PET+) ITNs were identified: 31 Afirma-tested (GEC = 20, GSC = 11) and 14 either underwent surgery (n = 13) or repeat FNA (Benign cytology) (n = 1) without Afirma. The prevalence of cancer and noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) including only resected nodules and ITN with repeat benign FNA (n = 33) was 36.4% (12/33). Excluding all Afirma "suspicious" non-resected ITNs and assuming all Afirma "benign" ITNs were truly benign, that prevalence was 28.6% (12/42). The BCR with GSC was 64% compared to 25% with GEC (p = 0.056). Combining GSC/GEC-tested ITNs, the BCR was higher in ITNs demonstrating low/very low-risk sonographic pattern by the American Thyroid Association (ATA) classification and ITNs scoring <4 by the American College of Radiology Thyroid Imaging, Reporting and Data System (ACR-TI-RADS) than ITNs with higher sonographic pattern/score (p = 0.025). CONCLUSIONS: The prevalence of cancer/NIFTP in (PET+) ITNs was 28.6-36.4% depending on the method of calculation. The BCR of Afirma GSC was 64%. Combining Afirma GEC/GSC-tested ITNs, BCR was higher in ITNs with a lower risk sonographic pattern.

[18F] Sodium Fluoride Dose Reduction Enabled by Digital Photon Counting PET/CT for Evaluation of Osteoblastic Activity.

The aim of the study was to assess the quality and reproducibility of reducing the injected [18F] sodium fluoride ([18F]NaF) dose while maintaining diagnostic imaging quality in bone imaging in a preclinical skeletal model using digital photon counting PET (dPET) detector technology. Beagles (n = 9) were administered three different [18F]NaF doses: 111 MBq (n = 5), 20 MBq (n = 5), and 1.9 MBq (n = 9). Imaging started ≃45 min post-injection for ≃30 min total acquisition time. Images were reconstructed using Time-of-Flight, ultra-high definition (voxel size of 1 × 1 × 1 mm3), with 3 iterations and 3 subsets. Point spread function was modeled and Gaussian filtering was applied. Skeleton qualitative and quantitative molecular image assessment was performed. The overall diagnostic quality of all images scored excellent (61%) and acceptable (39%) by all the reviewers. [18F]NaF SUVmean showed no statistically significant differences among the three doses in any of the region of interest assessed. This study demonstrated that a 60-fold [18F]NaF dose reduction was not significantly different from the highest dose, and it had not significant effect on overall image quality and quantitative accuracy. In the future, ultra-low dose [18F]NaF dPET/CT imaging may significantly decrease PET radiation exposure to preclinical subjects and personnel.

Enhancing Patient Experience With Internet Protocol Addressable Digital Light-Emitting Diode Lighting in Imaging Environments: A Phase I Study.

BACKGROUND: Conventional approaches to improve the quality of clinical patient imaging studies focus predominantly on updating or replacing imaging equipment; however, it is often not considered that patients can also highly influence the diagnostic quality of clinical imaging studies. Patient-specific artifacts can limit the diagnostic image quality, especially when patients are uncomfortable, anxious, or agitated. Imaging facility or environmental conditions can also influence the patient's comfort and willingness to participate in diagnostic imaging studies, especially when performed in visually unesthetic, anxiety-inducing, and technology-intensive imaging centers. When given the opportunity to change a single aspect of the environmental or imaging facility experience, patients feel much more in control of the otherwise unfamiliar and uncomfortable setting. Incorporating commercial, easily adaptable, ambient lighting products within clinical imaging environments allows patients to individually customize their environment for a more personalized and comfortable experience. OBJECTIVE: The aim of this pilot study was to use a customizable colored light-emitting diode (LED) lighting system within a clinical imaging environment and demonstrate the feasibility and initial findings of enabling healthy subjects to customize the ambient lighting and color. Improving the patient experience within clinical imaging environments with patient-preferred ambient lighting and color may improve overall patient comfort, compliance, and participation in the imaging study and indirectly contribute to improving diagnostic image quality. METHODS: We installed consumer-based internet protocol addressable LED lights using the ZigBee standard in different imaging rooms within a clinical imaging environment. We recruited healthy volunteers (n=35) to generate pilot data in order to develop a subsequent clinical trial. The visual perception assessment procedure utilized questionnaires with preprogrammed light/color settings and further assessed how subjects preferred ambient light and color within a clinical imaging setting. RESULTS: Technical implementation using programmable LED lights was performed without any hardware or electrical modifications to the existing clinical imaging environment. Subject testing revealed substantial variabilities in color perception; however, clear trends in subject color preference were noted. In terms of the color hue of the imaging environment, 43% (15/35) found blue and 31% (11/35) found yellow to be the most relaxing. Conversely, 69% (24/35) found red, 17% (6/35) found yellow, and 11% (4/35) found green to be the least relaxing. CONCLUSIONS: With the majority of subjects indicating that colored lighting within a clinical imaging environment would contribute to an improved patient experience, we predict that enabling patients to customize environmental factors like lighting and color to individual preferences will improve patient comfort and patient satisfaction. Improved patient comfort in clinical imaging environments may also help to minimize patient-specific imaging artifacts that can otherwise limit diagnostic image quality. TRIAL REGISTRATION: ClinicalTrials.gov NCT03456895; https://clinicaltrials.gov/ct2/show/NCT03456895.

Phase I Study of Veliparib on an Intermittent and Continuous Schedule in Combination with Carboplatin in Metastatic Breast Cancer: A Safety and [18F]-Fluorothymidine Positron Emission Tomography Biomarker Study.

BACKGROUND: Poly(ADP-ribose) polymerase inhibitors (PARPis) are U.S. Food and Drug Administration (FDA) approved for treatment of BRCA-mutated metastatic breast cancer. Furthermore, the BROCADE studies demonstrated benefit of adding an oral PARPi, veliparib, to carboplatin and paclitaxel in patients with metastatic breast cancer harboring BRCA mutation. Given multiple possible dosing schedules and the potential benefit of this regimen for patients with defective DNA repair beyond BRCA, we sought to find the recommended phase II dose (RP2D) and schedule of veliparib in combination with carboplatin in patients with advanced breast cancer, either triple-negative (TNBC) or hormone receptor (HR)-positive, human epidermal growth receptor 2 (HER2) negative with defective Fanconi anemia (FA) DNA-repair pathway based on FA triple staining immunofluorescence assay. MATERIALS AND METHODS: Patients received escalating doses of veliparib on a 7-, 14-, or 21-day schedule with carboplatin every 3 weeks. Patients underwent [18]fluoro-3'-deoxythymidine (18 FLT) positron emission tomography (PET) imaging. RESULTS: Forty-four patients (39 TNBC, 5 HR positive/HER2 negative with a defective FA pathway) received a median of 5 cycles (range 1-36). Observed dose-limiting toxicities were grade (G) 4 thrombocytopenia (n = 4), G4 neutropenia (n = 1), and G3 akathisia (n = 1). Common grade 3-4 toxicities included thrombocytopenia, lymphopenia, neutropenia, anemia, and fatigue. Of the 43 patients evaluable for response, 18.6% achieved partial response and 48.8% had stable disease. Median progression-free survival was 18.3 weeks. RP2D of veliparib was established at 250 mg twice daily on days 1-21 along with carboplatin at area under the curve 5. Patients with partial response had a significant drop in maximum standard uptake value (SUVmax ) of target lesions between baseline and early in cycle 1 based on 18 FLT-PET (day 7-21; ptrend = .006). CONCLUSION: The combination of continuous dosing of veliparib and every-3-week carboplatin demonstrated activity and an acceptable toxicity profile. Decrease in SUVmax on 18 FLT-PET scan during the first cycle of this therapy can identify patients who are likely to have a response. IMPLICATIONS FOR PRACTICE: The BROCADE studies suggest that breast cancer patients with BRCA mutation benefit from addition of veliparib to carboplatin plus paclitaxel. This study demonstrates that a higher dose of veliparib is tolerable and active in combination with carboplatin alone. With growing interest in imaging-based early response assessment, the authors demonstrate that decrease in [18]fluoro-3'-deoxythymidine positron emission tomography (FLT-PET) SUVmax during cycle 1 of therapy is associated with response. Collectively, this study established a safety profile of veliparib and carboplatin in advanced breast cancer while also providing additional data on the potential for FLT-PET imaging modality in monitoring therapy response.

Novel Peptide NIRF Optical Surgical Navigation Agents for HNSCC.

Head and neck squamous cell carcinoma (HNSCC) survival rates have not improved in a decade, with a 63% 5-year recurrence rate after surgery, making HNSCC a compelling indication for optical surgical navigation (OSN). A promising peptide, HN1, targeted and internalized in human HNSCC cells in multiple laboratories, but was slow (24 h) to accumulate. We modified HN1 and explored structural variables to improve the uptake kinetics and create IRdye800 adducts useful for OSN. Eleven new molecules were synthesized and characterized chemically, in human HNSCC cells (Cal 27), and in HNSCC xenograft mice. Cal 27 flank xenografts in Balb/c nude mice were imaged for 3-48 h after 40 nmol intravenous doses of IR800-labeled molecules. Cell uptake kinetics in the 1-2 h window incubated at 1-10 µM were independent of the dye label (FITC, Cy5, or IR800), but increased markedly with additional N-terminal lipophilic substitution, and after resequencing the peptide to separate polar amino acids and move the lysine-dye more centrally. Microscopy confirmed the strong Cal 27 cell binding and demonstrated primarily cytosolic and membrane localization of the fastest peptide, 4Iphf-HN17. 4Iph-HN17-IR800 showed 26-fold greater rate of uptake in cells than HN1-IR800, and far stronger OSN imaging intensity and tumor to background contrast in mice, suggesting that the new peptide is a promising candidate for OSN of HNSCC.

Emerging Opportunities for Digital PET/CT to Advance Locoregional Therapy in Head and Neck Cancer.

The purpose of this article is to present the recent imaging advancements enabled by digital photon counting positron emission tomography detector technology and discuss its potential applications in the clinical management of head and neck cancer (HNC) and nodal metastases. 18F-fluorodeoxyglucose positron-emission tomography is a clinically useful biomarker for the detection, targeted biopsy, treatment planning, and therapeutic response assessment of HNC. This article highlights the current state of 18F-fluorodeoxyglucose positron-emission tomography imaging in HNC management as well as the emerging capabilities of the recently introduced digital photon counting positron emission tomography/computed tomography platform for more effective molecular and functional HNC imaging.

Development of an orthotopic canine prostate cancer model expressing human GRPr.

BACKGROUND: Ace-1 canine prostate cancer cells grow orthotopically in cyclosporine immunosuppressed laboratory beagles. We previously transfected (human Gastrin-Releasing Peptide Receptor, huGRPr) into Ace-1 cells and demonstrated receptor-targeted NIRF imaging with IR800-G-Abz4-t-BBN, an agonist to huGRPr. Herein, we used the new cell line to develop the first canine prostate cancer model expressing a human growth factor receptor. METHODS: Dogs were immunosuppressed with cyclosporine, azathioprine, prednisolone, and methylprednisolone. Their prostate glands were implanted with Ace-1huGRPr cells. The implantation wounds were sealed with a cyanoacrylic adhesive to prevent extraprostatic tumor growth. Intraprostatic tumors grew in 4-5 week. A lobar prostatic artery was then catheterized via the carotid artery and 25-100 nmol IR800-Abz4-t-BBN was infused in 2 mL followed by euthanasia in dogs 1-2, and recovery for 24 h before euthanasia in dogs 3-6. Excised tissues were imaged optically imaged, and histopathology performed. RESULTS: Dog1 grew no tumors with cyclosporine alone. Using the four drug protocol, Dogs 2-6 grew abundant 1-2 mm intracapsular and 1-2 cm intraglandular tumors. Tumors grew >5 cm when the prostate cancer cells became extracapsular. Dogs 4-6 with sealed prostatic capsule implantation sites had growth of intracapsular and intraglandular tumors and LN metastases at 5 weeks. High tumor to background BPH signal in the NIRF images of sectioned prostate glands resulted from the 100 nmol dose (∼8 nmol/kg) in dogs 2-4 and 50 nmol dose in dog 5, but not from the 25 nmol dose in Dog 6. Imaging of mouse Ace-1huGRPr tumors required an intravenous dose of 500 nmol/kg body wt. A lymph node that drained the prostate gland was detectable in Dog 4. Histologic findings confirmed the imaging data. CONCLUSION: Ace-1huGRPr cells created viable, huGRPr-expressing tumors when implanted orthotopically into immune-suppressed dogs. Local delivery of an imaging agent through the prostatic artery allowed a very low imaging dose, suggesting that therapeutic agents could be used safely for treatment of early localized intraglandular prostate cancer as adjuvant therapy for active surveillance or focal ablation therapies, or for treating multifocal intraglandular disease where focal ablation therapies are not indicated or ineffective.

Advanced Functional Tumor Imaging and Precision Nuclear Medicine Enabled by Digital PET Technologies.

The purpose of this article is to provide a brief overview of the background, basic principles, technological evolution, clinical capabilities, and future directions for functional tumor imaging as PET evolves from the conventional photomultiplier tube-based platform into a fully digital detector acquisition platform. The recent introduction of solid-state digital photon counting PET detector is the latest evolution of clinical PET which enables faster time-of-flight timing resolution that leads to more precise localization of the annihilation events and further contributes to reduction in partial volume and thus makes high definition and ultrahigh definition PET imaging feasible with current standard acquisition procedures. The technological advances of digital PET can be further leveraged by optimizing many of the acquisition and reconstruction methodologies to achieve faster image acquisition to improve cancer patient throughput, lower patient dose in accordance with ALARA, and improved quantitative accuracy to enable biomarker capability. Digital PET technology will advance molecular imaging capabilities beyond oncology and enable Precision Nuclear Medicine.

Biological Evaluation of a Fluorescent-Imaging Agent for Medullary Thyroid Cancer in an Orthotopic Model.

Context: The primary and definitive treatment of medullary thyroid cancer (MTC) is surgical resection. Recurrent or residual disease is typically a result of incomplete surgical removal. Objective: Our objective is to develop a compound that assists in intraoperative visualization of cancer, which would have the potential to improve surgical cure rates and outcomes. Results: We report the biological characterization of Compound-17, which is labeled with IRdye800, allowing fluorescent visualization of MTC mouse models. We found that the agent has high affinity for two human MTC cell lines (TT and MZ-CRC1) in vitro and in vivo. We further tested the affinity of the compound in a newly developed MTC orthotopic xenograft model and found that Compound-17 produces fluorescent signals within MTC-derived orthotopic xenografts in comparison with a sequence-jumbled control compound and surrounding normal tissues. Conclusions: Compound-17 is a unique and effective molecule for MTC identification that may have therapeutic potential.

Clinical feasibility of 90Y digital PET/CT for imaging microsphere biodistribution following radioembolization.

PURPOSE: The purpose of this study was to evaluate the clinical feasibility of next generation solid-state digital photon counting PET/CT (dPET/CT) technology and imaging findings in patients following 90Y microsphere radioembolization in comparison with standard of care (SOC) bremsstrahlung SPECT/CT (bSPECT/CT). METHODS: Five patients underwent SOC 90Y bremsstrahlung imaging immediately following routine radioembolization with 3.5 ± 1.7 GBq of 90Y-labeled glass microspheres. All patients also underwent dPET/CT imaging at 29 ± 11 h following radioembolization. Matched pairs comparison was used to compare image quality, image contrast and 90Y biodistribution between dPET/CT and bSPECT/CT images. Volumetric assessments of 90Y activity using different isocontour thresholds on dPET/CT and bSPECT/CT images were also compared. RESULTS: Digital PET/CT consistently provided better visual image quality and 90Y-to-background image contrast while depicting 90Y biodistribution than bSPECT/CT. Isocontour volumetric assessment using a 1% threshold precisely outlined 90Y activity and the treatment volume on dPET/CT images, whereas a more restrictive 20% threshold on bSPECT/CT images was needed to obtain comparable treatment volumes. The use of a less restrictive 10% threshold isocontour on bSPECT/CT images grossly overestimated the treatment volume when compared with the 1% threshold on dPET/CT images. CONCLUSIONS: Digital PET/CT is clinically feasible for the assessment of 90Y microsphere biodistribution following radioembolization, and provides better visual image quality and image contrast than routine bSPECT/CT with comparable acquisition times. With further optimization and clinical validation, dPET technology may allow faster and more accurate imaging-based assessment of 90Y microsphere biodistribution.

Advancing Precision Nuclear Medicine and Molecular Imaging for Lymphoma.

PET with fluorodeoxyglucose F 18 (18F FDG-PET) is a meaningful biomarker for the detection, targeted biopsy, and treatment of lymphoma. This article reviews the evolution of 18F FDG-PET as a putative biomarker for lymphoma and addresses the current capabilities, challenges, and opportunities to enable precision medicine practices for lymphoma. Precision nuclear medicine is driven by new imaging technologies and methodologies to more accurately detect malignant disease. Although quantitative assessment of response is limited, such technologies will enable a more precise metabolic mapping with much higher definition image detail and thus may make it a robust and valid quantitative response assessment methodology.