Dual-tracer subtraction scintigraphy combined with SPECT/CT in preoperative patients with primary hyperparathyroidism

Abstract Introduction: Hyperparathyroidism is an endocrine disorder caused by overproduction of parathyroid hormone secreted from the parathyroid glands. Although this disorder is associated with a plethora of symptoms, the majority of people are now asymptomatic and discovered during routine laboratory screening. Aim: The study presents the diagnostic accuracy of our dual tracer subtraction parathyroid scintigraphy combined with SPECT/CT imaging protocol. Materials and methods: A retrospective study was conducted between June 1st, 2021, and June 1st, 2023. A cohort of 30 patients – 29 women (96.7%) and 1 man (3.3%), aged 37 to 86 years (mean: 61.2, standard deviation: 11.6) with clinical suspicion for primary hyperparathyroidism underwent parathyroid imaging for preoperative localization of parathyroid adenoma or ectopic parathyroid gland. Results: Twenty-six out of the thirty patients with primary hyperparathyroidism had positive scan results, while four patients had negative results. The results showed adenoma of the inferior parathyroid glands in 18 patients. Adenoma of the superior parathyroid glands was found in 3 patients. Ectopic parathyroid gland was found in 4 patients. In one patient multiglandular parathyroid involvement was observed. Planar scintigraphy was positive for presence of hyperfunctioning parathyroid in 15 patients (50%), whereas SPECT/CT imaging was positive in 26 patients (86.7%) and negative in 4 patients (13.3%). Conclusions: The combination of functional and morphological data obtained from a single examination through dual-radiopharmaceutical subtraction imaging and SPECT/CT allows increased diagnostic accuracy, which influences the choice of surgical technique and treatment result

Fully human monoclonal antibody targeting activated ADAM10 on colorectal cancer cells

Metastasis and chemoresistance in colorectal cancer are mediated by certain poorly differentiated cancer cells, known as cancer stem cells, that are maintained by Notch downstream signaling initiated upon Notch cleavage by the metalloprotease ADAM10. It has been shown that ADAM10 overexpression correlates with aberrant signaling from Notch, erbBs, and other receptors, as well as a more aggressive metastatic phenotype, in a range of cancers including colon, gastric, prostate, breast, ovarian, uterine, and leukemia. ADAM10 inhibition, therefore, stands out as an important and new approach to deter the progression of advanced CRC. For targeting the ADAM10 substrate-binding region, which is located outside of the catalytic domain of the protease, we generated a human anti-ADAM10 monoclonal antibody named 1H5. Structural and functional characterization of 1H5 reveals that it binds to the substrate-binding cysteine-rich domain and recognizes an activated ADAM10 conformation present on tumor cells. The mAb inhibits Notch cleavage and proliferation of colon cancer cell lines in vitro and in mouse models. Consistent with its binding to activated ADAM10, the mAb augments the catalytic activity of ADAM10 towards small peptide substrates in vitro. Most importantly, in a mouse model of colon cancer, when administered in combination with the therapeutic agent Irinotecan, 1H5 causes highly effective tumor growth inhibition without any discernible toxicity effects. Our singular approach to target the ADAM10 substrate-binding region with therapeutic antibodies could overcome the shortcomings of previous intervention strategies of targeting the protease active site with small molecule inhibitors that exhibit musculoskeletal toxicity