Can Whole-body MRI Replace CT in Management of Metastatic Testicular Cancer? A Prospective, Non-inferiority Study.

Purpose Concerns of imaging-related radiation in young patients with high survival rates have increased the use of magnetic resonance imaging (MRI) in testicular cancer (TC) stage I. However, computed tomography (CT) is still preferred for metastatic TC. The purpose of this study was to compare whole-body MRI incl. diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) with contrast-enhanced, thoracoabdominal CT in metastatic TC.Methods A prospective, non-inferiority study of 84 consecutive patients (median age 33 years) with newly diagnosed metastatic TC (February 2018 - January 2021). Exclusion criteria were age <18 years, claustrophobia and MRI contraindications. Patients had both MRI and CT before and after treatment. Anonymised images were reviewed by experienced radiologists.Lesion malignancy was evaluated on a Likert scale (1 benign – 4 malignant). Sensitivity, specificity, positive predictive value, negative predictive value and accuracy were calculated on patient and lesion level. For non-inferiority testing, the difference in sensitivity between CT and MRI was calculated. The level of significance was set at 5%. ROC curves and interobserver agreement were calculated.Results On patient level, MRI had 98% sensitivity and 75% specificity compared to CT. On lesion level within each modality, MRI had 99% sensitivity and 78% specificity, whereas CT had 98% sensitivity and 88% specificity. MRI sensitivity was non-inferior to CT (difference 0.57% (95% CI -1.4-2.5%)). The interobserver agreement was substantial between CT and MRI. Conclusion MRI with DWIBS was non-inferior to contrast-enhanced CT in detecting metastatic TC disease. Trial registration www.clinicaltrials.gov NCT03436901, finished July 1st 2021.

Biological Distribution of Orally Administered [123I]MIBG for Estimating Gastrointestinal Tract Absorption

Gastrointestinal tract absorption of cationic anticancer drugs and medicines was estimated using whole-body imaging following oral [123I]MIBG administration. [123I]MIBG was added to cultures of human embryonic kidney (HEK)293 cells expressing human organic anion transporting polypeptide (OATP)2B1, carnitine/organic cation transporter (OCTN)1 and OCTN2, and organic cation transporter (OCT)1, OCT2, and OCT3 with and without cimetidine (an OCTN and OCT inhibitor) and L-carnitine (an OCTN inhibitor). Biodistribution analyses and single-photon emission computed tomography (SPECT) imaging in normal and dextran sodium sulfate (DSS)-induced experimental colitis mice were conducted using [123I]MIBG with and without cimetidine. [123I]MIBG uptake was significantly higher in HEK293/OCTN1, 2, and OCT1-3 cells than in mock cells. Uptake via OCTN was inhibited by L-carnitine, whereas OCT-mediated uptake was inhibited by cimetidine. Biodistribution analyses and SPECT imaging studies showed significantly lower accumulation of [123I]MIBG in the blood, heart, liver, and bladder in DSS-induced experimental colitis mice and mice with cimetidine loading compared with normal mice, whereas significantly higher accumulation in the stomach and kidney was observed after [123I]MIBG injection. [123I]MIBG imaging after oral administration can be used to estimate gastrointestinal absorption in the small intestine via OCTN and/or OCT by measuring radioactivity in the heart, liver, and bladder.

Efficiency of Plasmon-Induced Dual-Mode Fluorescence Enhancement upon Two-Photon Excitation

Anisotropic noble metal nanoparticles supporting more than one localized surface plasmon resonance can be tailored for efficient dual-mode fluorescence enhancement by ensuring an adequate coupling to both absorption and emission bands of fluorophores. This approach is naturally extended to two-photon excitation fluorescence, where a molecule is excited by simultaneous nonlinear absorption of two photons. However, the relative impact of plasmon coupling to excitation and emission on the overall fluorescence enhancement can be very different in this case. Here, by using the finite-difference time-domain method, we study the two-photon excitation fluorescence of near-infrared fluorescent protein (NirFP) eqFP670, which is the most red-shifted NirFP to date, in proximity to a silver nanobar. By optimizing the length and aspect ratio of the particle, we reach a fluorescence enhancement factor of 103. We show that the single mode coupling regime with highly tuned near-field significantly outperforms the dual-mode coupling enhancement. The plasmon-induced amplification of the fluorophore’s excitation rate becomes of utmost importance due to its quadratic dependence on light intensity, defining the fluorescence enhancement upon two-photon excitation. Our results can be used for the rational design of hybrid nanosystems based on NirFP and plasmonic nanoparticles with greatly improved brightness important for developing whole-body imaging techniques.

Whole-Body Imaging to Assess Cell-Based Immunotherapy: Preclinical Studies with an Update on Clinical Translation

In the past decades, immunotherapies against cancers made impressive progress. Immunotherapy includes a broad range of interventions that can be separated into two major groups: cell-based immunotherapies, such as adoptive T cell therapies and stem cell therapies, and immunomodulatory molecular therapies such as checkpoint inhibitors and cytokine therapies. Genetic engineering techniques that transduce T cells with a cancer-antigen-specific T cell receptor or chimeric antigen receptor have expanded to other cell types, and further modulation of the cells to enhance cancer targeting properties has been explored. Because cell-based immunotherapies rely on cells migrating to target organs or tissues, there is a growing interest in imaging technologies that non-invasively monitor transferred cells in vivo. Here, we review whole-body imaging methods to assess cell-based immunotherapy using a variety of examples. Following a review of preclinically used cell tracking technologies, we consider the status of their clinical translation.

Prognostic Value of Serum Thyroglobulin and Anti-Thyroglobulin Antibody in Thyroid Carcinoma Patients following Thyroidectomy

Well-differentiated thyroid cancer (WDTC) is a malignant head and neck tumor with a very high incidence. Thyroidectomized WDTC patients have been referred to nuclear medicine for radioactive iodine (RAI) ablation therapy and/or annual follow-up with diagnostic whole-body imaging. Serum thyroglobulin (TG) and thyroglobulin antibodies (TGAb) are biochemical tumor markers used to monitor WDTC. A global rise in the prevalence of WDTC is increasing the number of thyroidectomized patients requiring lifelong monitoring for persistent or recurrent diseases. The present study aimed to identify the most successful prognostic factors in well-defined thyroid carcinoma patients following total thyroidectomy and RAI therapy, followed by an estimation of the cutoff value of TG and TGAb. In this context, a total of 100 subjects were recruited and classified as follows: 60 thyroid carcinoma patients underwent total thyroidectomy and successful RAI therapy, while 40 normal healthy individuals matched for age, sex, and socioeconomic status constituted the control group. Interestingly, the levels of TG did not differ significantly between the relapsed and non-relapsed cases, but the levels of TGAb differed significantly between the relapsed and non-relapsed cases. Collectively, TG and TGAb are considered the most successful prognostic factors in well-defined thyroid carcinoma patients after total thyroidectomy and RAI therapy. The present study also concluded that the TGAb determination was better than that of the TG level, with a cutoff value of 10 ng/mL. These findings provide baseline information for follow-up and lifelong monitoring of thyroidectomized WDTC patients. Further research is warranted to explore more about serum TG and TGAb in thyroid carcinoma patients on a larger scale.

Evaluation of single domain antibodies as nuclear tracers for imaging of the immune checkpoint receptor human lymphocyte activation gene-3 in cancer

Recent advancements in the field of immune-oncology have led to a significant increase in life expectancy of patients with diverse forms of cancer, such as hematologic malignancies, melanoma and lung cancer. Unfortunately, these encouraging results are not observed in the majority of patients, who remain unresponsive and/or encounter adverse events. Currently, researchers are collecting more insight into the cellular and molecular mechanisms that underlie these variable responses. As an example, the human lymphocyte activation gene-3 (huLAG-3), an inhibitory immune checkpoint receptor, is increasingly studied as a therapeutic target in immune-oncology. Noninvasive molecular imaging of the immune checkpoint programmed death protein-1 (PD-1) or its ligand PD-L1 has shown its value as a strategy to guide and monitor PD-1/PD-L1-targeted immune checkpoint therapy. Yet, radiotracers that allow dynamic, whole body imaging of huLAG-3 expression are not yet described. We here developed single-domain antibodies (sdAbs) that bind huLAG-3 and showed that these sdAbs can image huLAG-3 in tumors, therefore representing promising tools for further development into clinically applicable radiotracers.

Stack-Layer Dual-Element Ultrasonic Transducer for Broadband Functional Photoacoustic Tomography

Current Photoacoustic tomography (PAT) approaches are based on a single-element transducer that exhibits compromised performance in clinical imaging applications. For example, vascular, tumors are likely to have complicated shapes and optical absorptions, covering relatively wide spectra in acoustic signals. The wide ultrasonic spectra make it difficult to set the detection bandwidth optimally in advance. In this work, we propose a stack-layer dual-element ultrasonic transducer for PAT. The central frequencies of the two piezoelectric elements are 3.06 MHz (99.3% bandwidth at –6 dB) and 11.07 MHz (85.2% bandwidth at –6 dB), respectively. This transducer bridges the sensitivity capability of ultrasound and the high contrast of optical methods in functional photoacoustic tomography. The dual-element transducer enabled multiscale analysis of the vascular network in rat brains. Using a multi-wavelength imaging scheme, the blood oxygen saturation was also detected. The preliminary results showed the great potential of broad-bandwidth functional PAT on vascular network visualization. The method can also be extended to whole-body imaging of small animals, breast cancer detection, and finger joint imaging.