Challenges confronting sustainability in nuclear medicine practice.

BACKGROUND: Sustainability can be defined as the state in which consumption or depletion do not exceed regeneration. It can further be considered in five dimensions: environmental, economic, social, human resources, and ecological. KEY FINDINGS: There are a number of key issues that threaten sustainability across nuclear medicine clinical and research practices, and across the five dimensions of sustainability there is a requirement for compromise between conflicting priorities. Nonetheless, the field of nuclear medicine benefits from an inherent culture of innovation and forethought which fosters adaptation in order to achieve sustainability. CONCLUSION: The principles of sustainability are particularly challenging to navigate due to resource scarcity in nuclear medicine associated with both workforce shortages and supply disruptions. Specific challenges and adaptations are outlined for each of the five dimensions of sustainability. IMPLICATIONS FOR PRACTICE: There are opportunities for improving sustainability of nuclear medicine practice although success is reliant on a deeper understanding of the interplay across the five dimensions of sustainability.

The potential role of artificial intelligence in sustainability of nuclear medicine.

BACKGROUND: Strategies targeted at the five pillars of sustainability (social, human, economic, ecological and environmental) can be used to improve sustainability of clinical or research practices in nuclear medicine. KEY FINDINGS: While the core principle of sustainability is ensuring depletion does not exceed regeneration, this manuscript considers the balance of benefits and detriments of artificial intelligence (AI) technologies across the five pillars of sustainability. Specifically, innovations such as AI, generative AI and digital twins could enhance sustainability. While AI has the potential to address social asymmetry and inequity to drive the social and human pillars of sustainability, there is potential for widening the equity gap. AI augmentation and generative AI present economic and environmental sustainability opportunities. Deep digital twins offers clinical and research benefits in economic, ecological and environmental sustainability pillars. CONCLUSION: AI, digital twins and generative AI offer potential benefits to sustainability in nuclear medicine. Despite the benefits, caution is advised because these technologies confront a number of challenges that could potentially threaten sustainability. IMPLICATIONS FOR PRACTICE: AI presents opportunities for improving sustainability of nuclear medicine practice although caution is recommended to avoid unintentional undermining of sustainability across the five pillars.

Solitary Parathyroid Adenoma Localization in Technetium Tc99m Sestamibi SPECT and Multiphase Multidetector 4D CT.

BACKGROUND AND PURPOSE: Minimally invasive parathyroid surgery relies critically on image guidance, but data comparing the efficacy of various imaging modalities are scarce. Our aim was to perform a blinded comparison of the localizing capability of technetium Tc99m sestamibi SPECT, multiphase multidetector 4D CT, and the combination of these 2 modalities (technetium Tc99m sestamibi SPECT + multiphase multidetector 4D CT). MATERIALS AND METHODS: We reviewed the records of 31 (6 men, 25 women; median age, 56 years) consecutive patients diagnosed with biochemically confirmed primary hyperparathyroidism between November 2009 and March 2010 who underwent preoperative technetium Tc99m sestamibi SPECT and multiphase multidetector 4D CT performed on the same scanner with pathologic confirmation by resection of a single parathyroid adenoma. Accuracy was determined separately for localization to the correct side and quadrant using surgical localization as the standard of reference. RESULTS: Surgical resection identified 14 left and 17 right parathyroid adenomas and 2 left inferior, 12 left superior, 11 right inferior, and 6 right superior parathyroid adenomas. For left/right localization, technetium Tc99m sestamibi SPECT achieved an accuracy of 93.5% (29 of 31), multiphase multidetector 4D CT achieved 96.8% accuracy (30 of 31), and technetium Tc99m sestamibi SPECT + multiphase multidetector 4D CT achieved 96.8% accuracy (30 of 31). For quadrant localization, technetium Tc99m sestamibi SPECT accuracy was 67.7% (21 of 31), multiphase multidetector 4D CT accuracy was 87.1% (27 of 31), and technetium Tc99m sestamibi SPECT + multiphase multidetector 4D CT accuracy was 93.5% (29 of 31). Reader diagnostic confidence was consistently ranked lowest for technetium Tc99m sestamibi SPECT and highest for technetium Tc99m sestamibi SPECT + multiphase multidetector 4D CT. CONCLUSIONS: For left/right localization of parathyroid adenomas, all modalities performed equivalently. For quadrant localization, technetium Tc99m sestamibi SPECT + multiphase multidetector 4D CT is superior to technetium Tc99m sestamibi SPECT.

PET/CT today and tomorrow in veterinary cancer diagnosis and monitoring: fundamentals, early results and future perspectives.

Functional imaging using positron emission tomography (PET) plays an important role in the diagnosis, staging, image-guided treatment planning and monitoring of malignant diseases. PET imaging complements conventional anatomical imaging such as computed tomography (CT) and magnetic resonance imaging (MRI). The strength of CT scanning lies in its high spatial resolution, allowing for anatomical characterization of disease. PET imaging, however, moves beyond anatomy and characterizes tissue based on functions such as metabolic rate. Combined PET/CT scanners were introduced commercially in 2001 and a number of technological advancements have since occurred. Radiolabelled tracers such as (18)F-fluorodeoxyglucose (FDG) and (18)F-fluorothymidine (FLT) allow visualization of various metabolic processes within cancer cells. Many studies in human oncology evaluating the utility of PET/CT have demonstrated clinical benefits. Few veterinary studies have been performed, but initial studies show promise for improved detection of malignancy, more thorough staging of canine cancer and determination of early response and disease recrudescence.

Circulating tumor cells and bone metastases as detected by FDG-PET/CT in patients with metastatic breast cancer.

BACKGROUND: We evaluated the relationship between the detection and prognostic significance of circulating tumor cells (CTCs) and sites of metastases detected by 2-[fluorine-18]fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT) in patients with metastatic breast cancer (MBC). PATIENTS AND METHODS: From May 2004 to January 2008, 195 patients with relapsed/progressive MBC underwent whole-body FDG-PET/CT and provided blood samples for assessment of CTC count. RESULTS: Higher CTC numbers were detected in patients with bone metastases relative to those with no bone lesions (mean 65.7 versus 3.3, P = 0.0122) and in patients with multiple bone metastases relative to those with one or two bone lesions (mean 77.7 versus 2.6, P < 0.001). CTCs predicted overall survival (OS) in 108 patients with multiple sites of metastases including bone (P = 0.0008) but not in 58 without bone metastases (P = 0.4111) and in 29 with bone involvement only (P = 0.3552). All 15 patients but one with human epidermal growth factor receptor 2 (HER-2) positive tumors who were treated with trastuzumab-based regimens had <5 CTCs at progression. In multivariate analysis, CTCs, but not bone metastases, remained a significant predictor of OS. CONCLUSION: Presence of extensive bone metastases as detected by FDG-PET/CT is associated with increased CTC numbers in MBC.

Discoid lateral meniscus and the frequency of meniscal tears.

OBJECTIVE: To use MRI to determine the incidence of discoid lateral menisci in a large study population, and to compare those patients with those without a discoid meniscus in order to assess the impact of a discoid lateral meniscus on the frequency of meniscal tears. DESIGN AND PATIENTS: Results of 1,250 knee MRI studies were retrospectively reviewed. Using the criterion of three or more meniscal body segments on sequential sagittal images, 56 patients were found to have a discoid lateral meniscus. After exclusion of patients with prior knee surgery, 49 patients with a discoid lateral meniscus were compared with 1,146 patients without a discoid meniscus. Patients were categorized as having tears of the medial meniscus, lateral meniscus, or both menisci. RESULTS: In our study population, there was a 4.5% incidence of discoid lateral meniscus. Seventy-one percent of patients with a discoid lateral meniscus had one or more meniscal tears, compared with 54% of the comparison group (P=0.01). The frequency of solitary lateral meniscal tears in the discoid group was also higher than in the comparison group: 20%.versus 11% (P=0.03). The frequency of solitary medial meniscal tears and concomitant tears of both menisci were not significantly different between the two groups. CONCLUSIONS: The discoid lateral meniscus is an uncommon variant, but not as rare as once believed. Compared with the normal semilunar meniscus, the discoid lateral meniscus has a higher frequency of meniscal tears, and solitary tears of the lateral meniscus are more common in the discoid variant. The frequency of medial meniscal tears is not altered by the presence of a discoid lateral meniscus.

Tc-99m MDP uptake in a calcified bladder tumor.

A 68-year-old man with a history of prostate carcinoma and increasing levels of prostate-specific antigen was referred for a radionuclide bone scan. In addition to a probable metastatic lesion in the right femoral head, focal radiotracer accumulation was seen overlying the left aspect of the urinary bladder. Plain radiographs and pelvic computed tomography confirmed the presence of a calcified mass in the bladder. Cystoscopic examination revealed an exophytic bladder lesion. Biopsy indicated low-grade papillary transitional cell carcinoma, and the patient successfully underwent transurethral resection of this tumor.

Minor pocket B influences peptide binding, peptide presentation and alloantigenicity of H-2Kb.

Microsequence analysis of peptides eluted from the murine class I H-2Kb molecule together with the three-dimensional structure of the molecule co-crystallized with a homogeneous population of peptides suggests that pocket B is a minor pocket that does not play a major role in peptide presentation. This is in contrast to most other class I molecules in which pocket B plays a central role in selecting and presenting antigenic peptides. To investigate the role of pocket B in antigen presentation by the Kb molecule, we analyzed site-directed mutants of position 45 in pocket B for their effect on both allo- and peptide-specific recognition. We made an identical set of mutations in Kbm8 at residue 45 in order to evaluate their influence in the context of a more open pocket B which results from the bm8 substitution at amino acid 24 (E-->S). We demonstrated that this minor pocket did play a significant role in the antigenicity of both molecules and that this role was more readily apparent in the context of the more open pocket B of Kbm8. In addition, we found that some substitutions of residue 45 in the Kbm8 molecule restored recognition by some alloreactive and peptide specific anti-Kb T cell clones which are normally restricted to Kb, indicating that multiple configurations of amino acids in a pocket could result in similar binding and presentation capabilities.

Peptide-induced conformational changes in class I molecules. Direct detection by flow cytometry.

Activation of a T cell in response to peptide bound to class I MHC occurs by the sum of interactions across the area of contact between the TCR, the peptide, and class I MHC. It has been observed recently that substitution of the peptide residue at a position that is not accessible from the exterior of the class I molecule modulates T cell responses, raising the possibility that there may be indirect structural effects in the peptide-class I complex as a consequence of peptide binding. This report describes the use of mAbs to probe the conformation of the alpha 1 and alpha 2 domains of the mouse class I molecule Kb when bound to ovalbumin peptide and a panel of 19 peptide analogues that differ at position 2 (P2). By crystallographic data, side chains of this position are buried in the Ag binding cleft and have no direct access to the TCR. Substitution of position 2 results in a measurable change in conformation of the class I molecule, a change that correlates with the ability to stimulate T cells. This leads to a model that T cell activation by the peptide-class I complex may occur in three ways: 1) direct interaction of the TCR with the class I heavy chain, 2) direct interaction of the TCR with solvent-accessible peptide side chains, and 3) indirect interaction of peptide with TCR mediated via conformational perturbations in the class I complex.

Polymorphisms in pockets of major histocompatibility complex class I molecules influence peptide preference.

The set of peptides that is bound by a given major histocompatibility complex class I product can be described by one or two properly spaced anchor residues, and two properly spaced peptide termini, approximately 8-10 residues apart. Using radiolabeled peptide libraries, we examined whether mutations in those "pockets" in class I Kb molecules that do not seem critically involved in the interaction with the peptide anchor residues, do exert an effect on the set of preferred peptides. We find that mutations in all the pockets found in the structure of Kb have a significant effect on the peptide preference of the molecule, and their recognition by cytotoxic T cells. Alterations in substrate specificity are also observed for mutations involving residues that interact with main chain atoms in both peptide termini. These findings challenge a static view of the interaction of peptide termini with their respective pockets in the class I molecule, and imply a role for the minor pockets in peptide selectivity.

Amino acid changes in the peptide binding site have structural consequences at the surface of class I glycoproteins.

Structural changes on the surface of the class I Ag binding domain resulting from point mutations localized inside the Ag binding cleft of the H-2Kb and Kf glycoproteins were revealed using mAb. Both the loss and gain of antibody binding sites found among naturally occurring K glycoproteins resulted from single amino acid substitutions at a variety of different positions buried within the Ag binding groove. Each of the amino acid replacements analyzed represented naturally occurring diversity known to exist among the functional class I Ag-presenting molecules of the mouse. The binding of the affected mAb was not significantly altered in Kb molecules expressed by transfected T2 cells. Because T2 cells have been shown to express Kb molecules that are either largely devoid of bound peptides or bind a vastly different set of low affinity peptides, it is unlikely that the detected structural changes were caused by alterations in the spectrum of peptides bound by the class I variant glycoproteins. Similarly, a class I point mutant, Kb-97R, that also has been shown previously to bind a very different set of peptides in comparison to the parental Kb molecule also displays normal antibody binding properties. We conclude from these studies that structural diversity within the Ag binding cleft indirectly influences the external surface of the Ag-presenting domain of the class I H chain. Significantly, this surface is the interface between the T cell receptor and MHC molecules and may make contributions to the fine specificity of allorecognition.