Tilmanocept 50microgram kit for radiopharmaceutical preparation

Sentinel lymph node biopsy (SLNB) is a diagnostic staging procedure. The procedure aims to identify the first draining lymph node(s), which are most likely to contain metastases. SLNB is applied in various cancers, but not currently in thyroid carcinoma. However, treatment strategies are changing, making SLNB clinically relevant. SLNB may lead to more accurate staging, prevent unnecessary treatment and help achieve earlier curation. 68Ga-tilmanocept PET/computed tomography (CT) can better localize sentinel lymph nodes (SLNs) near the primary tumor than planar scintigraphy and single-photon emission computed tomography (SPECT)/CT. This paper describes the rationale and design of a study investigating SLNB using 68Ga-tilmanocept PET/CT and indocyanine-green-99mTc-nanocolloid in ten differentiated and medullary thyroid carcinoma patients. Localization and number of SLNs, pathology result, optimal scan protocol, surgical time and surgeon's experience are examined. Clinical Trial Registration: 2021-002470-42 (EudraCT).

Abstract licence: CC BY

Background Interstitial lung diseases (ILDs) include a large number of diseases associated with progressive pulmonary fibrosis (PPF), including idiopathic pulmonary fibrosis (IPF). Despite the rarity of each of the fibrotic ILDs individually, they cumulatively affect a considerable number of patients. PPF is characterised by an excessive collagen deposition leading to functional decline. Objectives Therapeutic options are limited to nintedanib and pirfenidone which are only able to reduce fibrosis progression. CD206-expressing M2 macrophages are involved in fibrosis progression, and whether they may be relevant therapeutic targets or biomarkers remains an open question. Results In our study, CD206 + lung macrophages were monitored in bleomycin-induced lung fibrosis in mice by combining flow cytometry, scRNAseq and in vivo molecular imaging using a single photon emission computed tomography (SPECT) radiopharmaceutical, 99m Tc-tilmanocept. The antifibrotic effect of the inhibition of M2 macrophage polarisation with a JAK inhibitor, tofacitinib, was assessed in vivo. We demonstrate that CD206-targeted in vivo SPECT imaging with 99m Tc-tilmanocept was able to accurately detect and quantify the increase in CD206 + macrophages from early to advanced stages of experimental fibrosis and ex vivo in lung biopsies from patients with IPF. CD206-targeted imaging also specifically detected a decrease in CD206 + lung macrophages on nintedanib and tofacitinib treatment. Importantly, early in vivo imaging of CD206 + macrophages allowed the prediction of experimental lung fibrosis progression as well as nintedanib and tofacitinib efficacy. Conclusions These findings indicate that M2 macrophages may be relevant theranostic targets for personalised medicine for patients with PPF.

Abstract licence: CC BY-NC

Abstract Purpose Sentinel lymph node (SLN) biopsy is rarely used for thyroid carcinoma staging. This is due to challenges associated with conventional Tc-99m-labeled tracers, often producing a large hotspot at the injection site, potentially hiding nearby SLNs (shine-through effect). The aim of this study was to demonstrate the feasibility and effectiveness of SLN visualization using the new PET tracer [ 68 Ga]Ga-tilmanocept. Methods Patients with thyroid carcinoma underwent ultrasound-guided peritumoral injection of [ 68 Ga]Ga-tilmanocept and ICG-[ 99m Tc]Tc-nanocolloid. [ 68 Ga]Ga-tilmanocept PET/CT scans were conducted at 15 min and 60 min post-injection to visualize the SLNs. SLN biopsy was performed using ICG-[ 99m Tc]TC-nanocolloid for intraoperative identification. The corresponding lymph node level was resected for reference. Results Seven differentiated thyroid carcinoma (DTC) and 3 medullary thyroid carcinoma (MTC) patients were included, of which 6 were clinically node-negative. The median number of SLNs detected on [ 68 Ga]Ga-tilmanocept PET/CT and resected was 3 (range 1–4) and 3 (range 1–5), respectively. Eight SLNs were found on PET/CT in the central compartment and 19 in the lateral compartment. The SLN procedure detected (micro)metastases in all patients except one. Seventeen of 27 pathologically assessed SLNs were positive, 8 negative, and 2 did not contain lymph node tissue, which led to upstaging in 5 out of 6 clinically node-negative patients. Conclusions [ 68 Ga]Ga-tilmanocept PET/CT identified SLNs in all patients, mainly in the lateral neck. The SLNs were successfully surgically detected and resected using ICG-[ 99m Tc]Tc-nanocolloid. This technique has the potential to improve neck staging, enabling more personalized treatment of thyroid cancer according to the lymph node status. Trial registration 2021–002470-42 (EudraCT).

Abstract licence: CC BY

Abstract Background Several studies have demonstrated varying rates of efficacy, reliability, and sensitivity of sentinel lymph node biopsy (SLNB) in identifying occult nodal disease for early stage oral cavity squamous cell carcinoma (OCSCC) depending on the radionuclide agent utilized. No head-to-head comparison of cost or clinical outcomes of SLNB when utilizing [ 99m Tc]tilmanocept versus [ 99m Tc]sulfur colloid has been performed. The goal of this study was to develop a decision model to compare the cost-effectiveness of [ 99m Tc]tilmanocept versus [ 99m Tc]sulfur colloid in early stage OCSCC. Patients and Methods A decision model of disease and treatment as a function of SLNB was created. Patients with a negative SLNB entered a Markov model of the natural history of OCSCC parameterized with published data to simulate five states of health and iterated over a 30-year time horizon. Treatment costs and quality-adjusted life-years (QALYs) for each health state were included. The incremental cost-effectiveness ratio (ICER) was then estimated using $100,000 per additional QALY as the threshold for determining cost-effectiveness. Results The base case cost-effectiveness analysis suggested [ 99m Tc]tilmanocept was more effective than [ 99m Tc]sulfur colloid by 0.12 QALYs (7.06 versus 6.94 QALYs). [ 99m Tc]Tilmanocept was more costly, with a lifetime cost of $84,961 in comparison with $84,264 for sulfur colloid, however, the overall base case ICER was $5859 per additional QALY, well under the threshold for cost-effectiveness. Multiple one-way sensitivity analyses were performed, and demonstrated the model was robust to alternative parameter values. Conclusion Our analysis showed that while [ 99m Tc]tilmanocept is more costly upfront, these costs are worth the additional QALYs gained by the use of [ 99m Tc]tilmanocept.

Abstract licence: CC BY

Sentinel lymph node biopsy (SLNB) is currently considered as a viable alternative to elective neck dissection (END) for the management of cN0 oral cavity squamous cell carcinoma (OCSCC). However, some difficulties were detected in sentinel lymph node (SLN) identification in floor of mouth (FOM) and ventral tongue tumors because of the so-called “shine-through radioactivity” of the injection site, which may mask nodal hotspots in proximity. We assessed the feasibility and the potential strengths of combining 99mTc-Tilmanocept with indocyanine green (ICG) fluorescence lympho-angiography in a dedicated multimodal protocol for SLNB in T1/T2N0 oral cancer to evaluate the synergistic role of each of these two tracers in providing the appropriate sensitivity and ease of learning, even in such a critical anatomical subsite. A detailed, stepwise description of our multimodal protocol is provided, together with the presentation of its application in two cases of early-stage ventral tongue tumors. Radioactive guidance with 99mTc-Tilmanocept was used preoperatively to perform planar lymphoscintigraphy and single-photon emission computed tomography/computed tomography and to define the nodal hotspot(s) and the surgical “roadmap”. In addition, it was used intraoperatively to pinpoint the SLN location within each nodal hotspot with high specificity but limited spatial resolution. Optical guidance with ICG injection at the tumor bed and near-infrared fluorescence imaging was then added, providing intuitive intraoperative guidance within each nodal hotspot with high spatial resolution. Our small experience with this protocol is illustrated and future perspectives are highlighted.

Abstract licence: CC BY