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Glioblastomas are the most common primary malignant grade 4 tumors of the central nervous system (CNS). The treatment and management of such tumors requires a multidisciplinary approach and nuclear medicine techniques play an important role in this process. Glioblastoma, which recurs despite current treatments and becomes resistant to treatments, is among the tumors with the lowest survival rate, with a survival rate of approximately 8 months. Currently, the standard treatment of glioblastoma is adjuvant chemoradiotherapy after surgical resection. There have been many recent advances in the field of Nuclear Medicine in glioblastoma. PET scans are critical in determining tumor localization, pre-surgical planning, evaluation of post-treatment response and detection of recurrence. Advances in the treatment of glioblastoma and a better understanding of the biological characteristics of the disease have contributed to the development of nuclear medicine techniques. This review, in addition to other studies, is intended as a general imaging summary guide and includes some new expressions discovered in glioblastoma. This review discusses recent advances in nuclear medicine in glioblastoma.

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In situ monitoring microRNA (miRNA) expression in vivo holds immense potential for directly visualizing the occurrence and progression of tumors. However, the significant barrier to developing a probe that can overcome the low abundance of miRNAs while providing an output signal with unlimited tissue penetration depth remains formidable. In this study, we developed a DNA machine-based magnetic resonance imaging nanoprobe (MRINP) for amplified detection of miR-21 in vivo. The MRINP was constructed with superparamagnetic Fe3O4 nanoparticles (NPs), paramagnetic Gd-DOTA complexes, and miR-21-activated DNA machines; the DNA machine was composed of hairpin DNAzyme (HD) strands serving as the DNAzyme walker and hairpin substrate (HS) strands serving as the track. Once uptake into tumor cells, the intracellular miR-21 specifically recognized and hybridized with the HD strand, restoring the activity of DNAzyme. Subsequently, the DNAzyme walker autonomously traveled on the surface of MRINP, and each step movement of the DNAzyme walker resulted in the cleavage of its substrate strands and the ensued release of the Gd-DOTA complex-labeled oligonucleotides, turning on the T1 signal of Gd-DOTA complexes for in situ imaging of miR-21 in tumor-bearing mice. This strategy would offer a promising approach for mapping tumor-specific biomarkers in vivo with unlimited penetration depth.

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We depict a unique case of a 39-year-old woman who presented to the emergency department with complaints of right upper quadrant pain. Work-up and a computed tomography (CT) scan revealed acute cholecystitis and the patient underwent laparoscopic cholecystectomy without complication. At this time, an incidental mass was discovered in the subcutaneous fat adjacent to the abdominal wall. The patient returned six months later with progressive, cyclic abdominal pain since her last hospital admission. Initial admission lab work was within normal limits and a urine pregnancy test was negative. Physical exam revealed tenderness around her previous cesarean section scar. Repeat CT revealed an enlarging, spiculated mass adherent to the abdominal wall. After imaging confirmation, the patient underwent complete open surgical excision for the removal of the mass. Post-surgical biopsy confirmed endometrial gland and stroma consistent with abdominal wall endometrioma. The patient was discharged with adjuvant therapy and recommended follow-up with the surgeon and her obstetrician-gynecologist. The radiological diagnosis, guidelines, and decision-making for initiating interventional treatment are discussed in this report. Our purpose in documenting this case is to present a rare diagnosis of an atypical location for an endometrioma on the abdominal wall, in a patient with prior cesarean delivery. Although this patient was treated with open excision, different interventional radiology treatments from radiofrequency ablation and focused ultrasound were discussed. In doing so, we hope to contribute to the systematic literature review on surgical excision as a treatment option for Pfannenstiel incision endometrioma.

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The primary challenges in tumor imaging and therapy revolve around improving targeting efficiency, enhancing probe/drug delivery efficacy, and minimizing off-target signals and toxicity. Although various carriers have been developed, many are difficult to synthesize, costly, and not universally applicable. Furthermore, numerous carriers exhibit limited delivery rates in solid tumors, particularly larger nanocarriers. To address these challenges, a simple binary co-assembly drug delivery platform has been designed using the readily synthesized small molecule Cys(SEt)-Lys-CBT (CKCBT) as the self-assembly building block. CKCBT can effectively penetrate tumor cells due to its positively charged Lys side chain and small size. Upon glutathione reduction, CKCBT co-assembles with Nile red or Chlorin e6 to form nanofibers inside tumor cells. This enables their specific accumulation in tumor cells rather than normal cells and extends their exposure time, resulting in precise and enhanced tumor imaging and treatment. Hence, this uncomplicated and highly efficient binary co-assembly drug delivery platform can be easily adapted to a broad spectrum of probes and drugs, presenting a novel approach for advancing clinical diagnosis and therapy.

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Human NAD(P)H-quinone oxidoreductase1 (HNQO1) is a two-electron reductase antioxidant enzyme whose expression is driven by the NRF2 transcription factor highly active in the prooxidant milieu found in human malignancies. The resulting abundance of NQO1 expression (up to 200-fold) in cancers and a barely detectable expression in body tissues makes it a selective marker of neoplasms. NQO1 can catalyze the repeated futile redox cycling of certain natural and synthetic quinones to their hydroxyquinones, consuming NADPH and generating rapid bursts of cytotoxic reactive oxygen species (ROS) and H2O2. A greater level of this quinone bioactivation due to elevated NQO1 content has been recognized as a tumor-specific therapeutic strategy, which, however, has not been clinically exploited. We review here the natural and new quinones activated by NQO1, the catalytic inhibitors, and the ensuing cell death mechanisms. Further, the cancer-selective expression of NQO1 has opened excellent opportunities for distinguishing cancer cells/tissues from their normal counterparts. Given this diagnostic, prognostic, and therapeutic importance, we and others have engineered a large number of specific NQO1 turn-on small molecule probes that remain latent but release intense fluorescence groups at near-infrared and other wavelengths, following enzymatic cleavage in cancer cells and tumor masses. This sensitive visualization/quantitation and powerful imaging technology based on NQO1 expression offers promise for guided cancer surgery, and the reagents suggest a theranostic potential for NQO1-targeted chemotherapy.

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The diagnosis and treatment of triple negative breast cancer (TNBC) are huge challenges due to the lack of identifiable molecular targets. The high expression of Nectin4 in a variety of tumors, including TNBC, is associated with the occurrence, invasion, progression and poor prognosis of tumors. Therefore, Nectin4 is an emerging biomarker for the diagnosis and treatment of TNBC. A PET imaging method to non-invasively quantify Nectin4 expression levels may aid in TNBC diagnosis and classification. In this study, a novel bicyclic peptide molecular probe [68Ga]Ga-DN68 was used to evaluate the expression of Nectin4 in tumors. The radiolabeling rate of [68Ga]Ga-DN68 was over 97 %, while maintaining more than 99 % radiochemical purity. In vitro experiments showed that [68Ga]Ga-DN68 could effectively target Nectin4 in tumor cells, and the cellular uptake of MC38-Nectin4 cells (Nectin4+) was significantly higher than that of MC38 cells (Nectin4-). Biodistribution and PET imaging studies consistently showed that [68Ga]Ga-DN68 was specifically accumulated in MC38-Nectin4 and MDA-MB-468 tumors, which was significantly higher than that of MC38. When co-injected with cold DN68, the specific accumulation could block the tumor uptake of MDA-MB-468. Notably, the signal-to-noise ratio at the tumor site gradually increased over time, reaching a peak at 1 h. These results strongly suggest that [68Ga]Ga-DN68 has broad application prospects as a PET tracer in TNBC imaging.

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Unilateral hypertrophy of the Tensor Fasciae Latae (TFL) muscle is a rare condition often characterized by a palpable mass in the lower limbs or hip pain. Despite its rarity, several causative factors have been identified, necessitating accurate diagnosis and appropriate management. Here, we present the case of a 53-year-old patient who sought outpatient consultation for a mass in the anterolateral aspect of the right thigh. Through this case study, we aim to contribute to the limited literature on this condition by discussing our diagnostic approach, management plan, and outcomes. Upon presentation, the patient underwent a thorough physical examination, revealing a non-tender, sessile mass seemingly originating in the deep connective tissue of the thigh. A magnetic resonance image (MRI) was performed to confirm the diagnosis and assess the extent of muscle involvement. This noninvasive modality provided valuable insights into the nature and localization of the mass, providing the diagnosis and guiding subsequent management decisions. Given the benign nature of the condition and absence of associated symptoms, conservative management was favored. Physical therapy focusing on stretching and strengthening exercises was initiated to address the underlying probable causes and improve functional capacity. Close monitoring through regular follow-up appointments was also recommended to track the progression of the hypertrophy and ensure symptomatic relief. Unilateral hypertrophy of the TFL muscle is a rare entity that presents diagnostic and management challenges. Through our case study, we have highlighted the importance of a comprehensive diagnostic workup, including imaging studies, in confirming the diagnosis and guiding management decisions. Conservative approaches, such as physical therapy, can effectively manage symptoms and improve quality of life in affected individuals. Continued research and documentation of cases are essential to expand our understanding of this condition and refine treatment strategies.

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Cancer presents a formidable challenge in modern medicine due to the intratumoral heterogeneity and the dynamic microenvironmental niche. Natural or genetically engineered oncolytic bacteria have always been hailed by scientists for their intrinsic tumor-targeting and oncolytic capacities. However, the immunogenicity and low toxicity inevitably constrain their application in clinical practice. When nanomaterials, characterized by distinctive physicochemical properties, are integrated with oncolytic bacteria, they achieve mutually complementary advantages and construct efficient and safe nanobiohybrids. In this review, we initially analyze the merits and drawbacks of conventional tumor therapeutic approaches, followed by a detailed examination of the precise oncolysis mechanisms employed by oncolytic bacteria. Subsequently, we focus on harnessing nanomaterial-assisted oncolytic bacteria (NAOB) to augment the effectiveness of tumor therapy and utilizing them as nanotheranostic agents for imaging-guided tumor treatment. Finally, by summarizing and analyzing the current deficiencies of NAOB, this review provides some innovative directions for developing nanobiohybrids, intending to infuse novel research concepts into the realm of solid tumor therapy.

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Meticulously engineered nanomaterials achieve significant advances in the diagnosis and therapy of solid tumors by improving tumor delivery efficiency; and thereby, enhancing imaging and therapeutic efficacy. Currently, polydopamine (PDA) attracts widespread attention because of its biocompatibility, simplicity of preparation, abundant surface groups, and high photothermal conversion efficiency, which can be applied in drug delivery, photothermal therapy, theranostics, and other nanomedicine fields. Inspired by PDA structures that are rich in catechol and amino functional groups that can coordinate with various metal ions, which have charming qualities and characteristics, metal-coordinated PDA structures are exploited for tumor theranostics, but are not thoroughly summarized. Herein, this review summarizes the recent progress in the fabrication of metal-coordinated PDA structures and their availabilities in tumor imaging and therapy, with further in-depth discussion of the challenges and future perspectives of metal-coordinated PDA structures, with the aim that this systematic review can promote interdisciplinary intersections and provide inspiration for the further growth and clinical translation of PDA materials.

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Deep vein thrombosis (DVT) is a type of venous thromboembolism that usually involves a clot formation in the deep veins of the lower extremities. Its formation is linked to Virchow's Triad which factors in venous stasis, endothelial damage, and hypercoagulability. Venous stasis is the primary factor contributing to the development of DVT and it refers to varicosity, external pressure placed on the extremity, or immobilization due to bed rest or long flights. Clinical presentation of DVT depends on the extent and location of the thrombus with common signs including localized swelling, pain, warmth, and edema. The Wells criteria are typically applied to assess the likelihood of thrombus formation alongside D-dimer assay, ultrasound, or CT imaging. As previously mentioned, these mostly occur in the lower extremities. However, upper extremity DVT has been noted and has been linked to inherited issues with coagulation and autoimmune disorders. This report will discuss a case of left-arm DVT in a patient who underwent bilateral mastectomy with sentinel node biopsy for a diagnosis of ductal carcinoma in situ in the left breast.

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PD-L1 is expressed in many tumors but rarely in normal tissues, therefore, it can be a target of PET imaging. In this work, we developed new peptide-based PET probes [18F]AlF-PAI-PDL1p and [68Ga]Ga-PAI-PDL1p with yields of 20-25 % and 40-55 %, respectively. [18F]AlF-PAI-PDL1p and [68Ga]Ga-PAI-PDL1p were synthesized within 30 min with high molar activities. [18F]AlF-PAI-PDL1p and [68Ga]Ga-PAI-PDL1p showed good stability in vivo and in vitro. In vitro cell studies showed [18F]AlF-PAI-PDL1p and [68Ga]Ga-PAI-PDL1p target PD-L1 specifically, with high uptake of 61.52 ± 4.39 and 19.29 ± 2.17 %ID/1 million cells in B16F10 cells at 60 min, respectively. Biodistribution results showed that both [18F]AlF-PAI-PDL1p and [68Ga]Ga-PAI-PDL1p had lower liver accumulation. In vivo PET imaging results showed that [18F]AlF-PAI-PDL1p had a high tumor uptake of 4.23 ± 0.81 %ID/g at 2 h and increased uptake of 6.60 ± 1.01 %ID/g at 12 h. [68Ga]Ga-PAI-PDL1p also showed high tumor uptake of 2.30 ± 0.20 %ID/g at 2 h and slightly increased uptake of 3.80 ± 0.26 %ID/g at 6 h. In conclusion, [18F]AlF-PAI-PDL1p and [68Ga]Ga-PAI-PDL1 seemed to be potential tracers for PET imaging of PD-L1 expression.

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Background: Nanoparticles conjugated with fluorescent probes have versatile applications, serving not only for targeted fluorescent imaging but also for evaluating the in vivo profiles of designed nanoparticles. However, the relationship between fluorophore density and nanoparticle behavior remains unexplored. Methods: The IR783-modified liposomes (IR783-sLip) were prepared through a modified ethanol injection and extrusion method. The cellular uptake efficiency of IR783-sLip was characterized by flow cytometry and fluorescence microscope imaging. The effects of IR783 density on liposomal in vivo behavior were investigated by pharmacokinetic studies, biodistribution studies, and in vivo imaging. The constitution of protein corona was analyzed by the Western blot assay. Results: Dense IR783 modification improved cellular uptake of liposomes in vitro but hindered their blood retention and tumor imaging performance in vivo. We found a correlation between IR783 density and protein corona absorption, particularly IgM, which significantly impacted the liposome performance. Meanwhile, we observed that increasing IR783 density did not consistently improve the effectiveness of tumor imaging. Conclusions: Increasing the density of modified IR783 on liposomes is not always beneficial for tumor near-infrared (NIR) imaging yield. It is not advisable to prematurely evaluate novel nanomaterials through fluorescence dye conjugation without carefully optimizing the density of the modifications.

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Despite various efforts to optimize the near-infrared (NIR) performance of perylene diimide (PDI) derivatives for bio-imaging, convenient and efficient strategies to amplify the fluorescence of PDI derivatives in biological environment and the intrinsic mechanism studies are still lacking. Herein, we propose an alkyl-doping strategy to amplify the fluorescence of PDI derivative-based nanoparticles for improved NIR fluorescence imaging. The developed PDI derivative, OPE-PDI, shows much brighter in n-Hexane (HE) compared with that in other organic media, and the excited state dynamics investigation experimentally elucidates the solvent effect-induced suppression of intermolecular energy transfer and intramolecular nonradiative decay as the underlying mechanism for the fluorescence improvement. Theoretical calculations reveal the lowest reorganization energies of OPE-PDI in HE among various solvents, indicating the effectively suppressed conformational relaxation to support the strongest radiative decay. Inspired by this, an alkyl atmosphere mimicking HE is constructed by incorporating the octadecane into OPE-PDI-based nanoparticles, permitting up to 3-fold fluorescence improvement compared with the counterpart nanoparticles. Owing to the merits of high brightness, anti-photobleaching, and low biotoxicity for the optimal nanoparticles, they have been employed for probing and long-term monitoring of tumor. This work highlights a facile strategy for the fluorescence enhancement of PDI derivative-based nanoparticles.

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Photoacoustic imaging (PAI) is an emerging modality in biomedical imaging with superior imaging depth and specificity. However, PAI still has significant limitations, such as the background noise from endogenous chromophores. To overcome these limitations, we developed a covalent activity-based PAI probe, NOx-JS013, targeting NCEH1. NCEH1, a highly expressed and activated serine hydrolase in aggressive cancers, has the potential to be employed for the diagnosis of cancers. We show that NOx-JS013 labels active NCEH1 in live cells with high selectivity relative to other serine hydrolases. NOx-JS013 also presents its efficacy as a hypoxia-responsive imaging probe in live cells. Finally, NOx-JS013 successfully visualizes aggressive prostate cancer tumors in mouse models of PC3, while being negligibly detected in tumors of non-aggressive LNCaP mouse models. These findings show that NOx-JS013 has the potential to be used to develop precision PAI reagents for detecting metastatic progression in various cancers.

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Hibernomas, rare benign tumors originating from brown adipose tissue, pose diagnostic challenges due to their infrequent occurrence and slow growth. We present a case of a 38-year-old woman with a progressively enlarging mass in her right lateral chest wall, initially stable in size but growing during pregnancy and causing pain and functional impairment. Radiological evaluation, including x-ray and MRI, provided inconclusive results, necessitating a biopsy for a definitive diagnosis. Ultrasound-guided needle aspiration biopsy revealed typical histopathological features consistent with hibernoma. A subsequent total surgical excision with negative margins was performed. The patient achieved complete recovery without recurrence during two years of follow-up. This case underscores the importance of considering hibernoma in the differential diagnosis of adipose tissue tumors, particularly in atypical clinical presentations. Moreover, it highlights the challenges in diagnosing and managing hibernomas and emphasizes the role of MRI and biopsy in achieving accurate diagnosis and optimal treatment outcomes. Continued reporting of such cases is crucial for increasing awareness and improving the management of this rare tumor.

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Maximizing treatment efficacy and forecasting patient prognosis in cancer necessitates the strategic use of targeted therapy, coupled with the prompt precise detection of malignant tumors. Theutilizationof gaseous systems as an adaptable platform for creating nanobubbles (NBs) has garnered significant attention as theranostics, which involve combining contrast chemicals typically used for imaging with pharmaceuticals to diagnose and treattumorssynergistically in apersonalizedmanner for each patient. This review specifically examines the utilization of oxygen NBsplatforms as a theranostic weapon in the field of oncology. We thoroughly examine the key factors that impact the effectiveness of NBs preparations and the consequences of these treatment methods. This review extensively examines recent advancements in composition schemes, advanced developments in pre-clinical phases, and other groundbreaking inventions in the area of NBs. Moreover, this review offers a thorough examination of the optimistic future possibilities, addressing prospective methods for improvement and incorporation into widely accepted therapeutic practices. As we explore the ever-changing field of cancer theranostics, the incorporation of oxygen NBs appears as a promising development, providing new opportunities for precision medicine and marking a revolutionary age in cancer research and therapy.

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Photoacoustic computed tomography (PACT), an emerging imaging modality in preclinical cancer research, can provide multiparametric 3D information about structures, physiological functions, and pharmacokinetics. Here, we demonstrate the use of high-definition 3D multiparametric PACT imaging of both primary and metastatic tumors in living mice to noninvasively monitor angiogenesis, carcinogenesis, hypoxia, and pharmacokinetics. The high-definition PACT system with a 1024-element hemispherical ultrasound transducer array provides an isotropic spatial resolution of 380 µm, an effective volumetric field-of-view of 12.8 mm × 12.8 mm × 12.8 mm without scanning, and an acquisition time of <30 s for a whole mouse body. Initially, we monitor the structural progression of the tumor microenvironment (e.g., angiogenesis and vessel tortuosity) after tumor cell inoculation. Then, we analyze the change in oxygen saturation of the tumor during carcinogenesis, verifying induced hypoxia in the tumor's core region. Finally, the whole-body pharmacokinetics are photoacoustically imaged after intravenous injection of micelle-loaded IR780 dye, and the in vivo PACT results are validated in vivo and ex vivo by fluorescence imaging. By employing the premium PACT system and applying multiparametric analyses to subcutaneous primary tumors and metastatic liver tumors, we demonstrate that this PACT system can provide multiparametric analyses for comprehensive cancer research.

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The sensitivity and diagnostic accuracy of magnetic resonance imaging mainly depend on the relaxation capacity of contrast agents (CAs) and their accumulated amount at the pathological region. Due to the better biocompatibility and high-spin capacity, Fe-complexes have been studied widely as an alternative to replace popular Gd-based CAs associated with potential biotoxicity. Compared with a variety of Fe complex-based CAs, such as small molecular, macrocyclic, multinuclear complexes, the form of nanoparticle exhibits outstanding longitudinal relaxation, but the clinical transformation was still limited by the inconspicuous difference of contrast between tumor and normal tissue. The enhanced effect of contrast is a positive relation as relaxation of CAs and their concentration in desired region. To specifically improve the amount of CAs accumulated in the tumor, pH-responsive polymer poly(2-ethyl-2-oxazoline) (PEOz) was modified on melanin, a ubiquitous natural pigment providing much active sites for chelating with Fe(III). The Fe(III)-Mel-PEOz we prepared could raise the tumor cell endocytosis efficiency via switching surface charge from anion to cation with the stimuli of the decreasing pH of tumor microenvironment. The change of pH has negligible effect on ther1of Fe(III)-Mel-PEOz, which is always maintained at around 1.0 mM-1s-1at 0.5 T. Moreover, Fe(III)-Mel-PEOz exhibited low cytotoxicity, and satisfactory enhancement of positive contrast effectin vivo. The excellent biocompatibility and stable relaxation demonstrate the high potential of Fe(III)-Mel-PEOz in the diagnosis of tumor.

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O-([18F]Fluoroethyl)-l-tyrosine ([18F]FET) is actively transported into the brain and cancer cells by LAT1 and possibly other amino acid transporters, which enables brain tumor imaging by positron emission tomography (PET). However, tumor delivery of this probe in the presence of competing amino acids may be limited by a relatively low affinity for LAT1. The aim of the present work was to evaluate the meta-substituted [18F]FET analog m-[18F]FET and the methyl ester [18F]FET-OMe, which were designed to improve tumor delivery by altering the physicochemical, pharmacokinetic, and/or transport properties. Both tracers could be prepared with good radiochemical yields of 41-56% within 66-90 min. Preclinical evaluation with [18F]FET as a reference tracer demonstrated reduced in vitro uptake of [18F]FET-OMe by U87 glioblastoma cells and no advantage for in vivo tumor imaging. In contrast, m-[18F]FET showed significantly improved in vitro uptake and accelerated in vivo tumor accumulation in an orthotopic glioblastoma model. As such, our work identifies m-[18F]FET as a promising alternative to [18F]FET for brain tumor imaging that deserves further evaluation with regard to its transport properties and in vivo biodistribution.

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In clinical practice, tumor-targeting diagnosis and immunotherapy against programmed death ligand 1 (PD-L1) have a significant impact. In this research, a PD-L1-antagonistic affibody dimer (ZPD-L1) was successfully prepared through Escherichia coli expression system, and conjugated with the photosensitizer of ICG via N-hydroxysuccinimide (NHS) ester to develop a novel tumor-targeting agent (ICG-ZPD-L1) for both tumor imaging diagnosis and photothermal-immunotherapy simultaneously. In vitro, ZPD-L1 could specifically bind to PD-L1-positive LLC and MC38 tumor cells, and ICG-ZPD-L1-mediated photothermal therapy (PTT) also showed excellent phototoxicity to these tumor cells. In vivo, ICG-ZPD-L1 selectively enriched into the PD-L1-positive MC38 tumor tissues, and the high-contrast optical imaging of tumors was obtained. ICG-ZPD-L1-mediated PTT exhibited a potent anti-tumor effect in vivo due to its remarkable photothermal properties. Furthermore, ICG-ZPD-L1-mediated PTT significantly induced the immunogenic cell death (ICD) of primary tumors, promoted maturation of dendritic cells (DCs), up-regulated anti-tumor immune response, enhanced immunotherapy, and superiorly inhibited the growth of metastatic tumors. In addition, ICG-ZPD-L1 showed favorable biosafety throughout the brief duration of treatment. In summary, these results suggest that ICG-ZPD-L1 is a multifunctional tumor-targeting drug integrating tumor imaging diagnosis and photothermal-immunotherapy, and has great guiding significance for the diagnosis and treatment of clinical PD-L1-positive tumor patients.

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