Preoperative Serum Thyroglobulin Levels Predict Radioiodine Therapy Outcome in Papillary Thyroid Microcarcinoma Patients.

Our previous study showed that elevated preoperative thyroglobulin (pre-Tg) level predicted the risk of developing radioiodine refractory in PTC patients. In the present study, we aimed to evaluate the prognostic value of pre-Tg in papillary thyroid microcarcinoma (PTMC). After a specific inclusion and exclusion criteria were applied, a total of 788 PTMCs were enrolled from Jiangyuan Hospital affiliated to Jiangsu Institute of Nuclear Medicine between Jan 2015 and Dec 2019. Among them, 107 PTMCs were treated with radioiodine therapy (RAIT) and the response to therapy was grouped as excellent response (ER), and non-excellent response (NER: indeterminate response, IDR and biochemical incomplete response, BIR). Multivariable logistic regression was used to identify predictors for the response of RAIT in PTMCs. Higher pre-Tg levels were detected in PTMCs with RAIT as compared with PTMCs without RAIT (p=0.0018). Higher levels of pre-Tg were also found in patients with repeated RAIT as compared with patients with single RAIT (p<0.0001). Furthermore, pre-Tg level was higher in PTMC with IDR (n=16) and much higher in BIR (n=9) as compared with patients with ER (n=82, p=0.0003) after RAIT. Multivariate analysis showed that pre-Tg level over 16.79 ng/ml [OR: 6.55 (2.10-20.39), p=0.001] was the only independent predictor for NER in PTMC with RAIT. We found that high level of pre-Tg predicted a poor RAIT outcome in PTMC. Our finding explores a prospective way in identifying high-risk PTMCs with poor response to RAIT.

Preparation and in vivo biological investigations on a novel radioligand for bone scanning: technetium-99m-labeled zoledronic acid derivative.

INTRODUCTION: To enable imaging at an earlier time after injection, a radiopharmaceutical with higher affinity for bone, larger ratio of bone-to-soft tissue uptake and more rapid clearance from blood is required. The nature of diphosphonic acid is a key factor to determine the advantages of the radiopharmaceuticals. The purpose of this study is to optimize the linker chain between the imidazolyl and geminal diphosphonate group in the zoledronic acid (ZL) to develop novel single photon emission computed tomography (SPECT) bone imaging agent. METHODS: A novel ZL derivative, 1-hydroxy-3-(1H-imidazol-1-yl)propane-1,1-diyldiphosphonic acid (IPrDP), was successfully prepared and labeled with (99m)Tc in a high labeling yield. Biodistribution of (99m)Tc-IPrDP and (99m)Tc-ZL in normal mice were studied and compared. SPECT bone scanning was performed on the rabbit and a series of dynamic and static images were recorded by Philips SKY Light emission computed tomography. RESULTS: In the biodistribution studies, (99m)Tc-IPrDP exhibits significant advantages on the bone resorption and the clearance from soft tissues compared with (99m)Tc-ZL. Kinetics of blood clearance in mice showed that T(1/2α) and T(1/2ß) of (99m)Tc-IPrDP were 1.47 min and 46.47 min, while those of (99m)Tc-ZL were 2.28 and 52.63 min respectively. Excellent images of the rabbit skeleton can be quickly obtained for (99m)Tc-IPrDP, which was faster than (99m)Tc-ZL and the clinically widely used bone imaging agent (99m)Tc-MDP (technetium-99m labeled with methylenediphosphonate). CONCLUSIONS: (99m)Tc-IPrDP possesses excellent characteristics for the potential application as a novel bone scanning agent.

Animal studies of 99mTc-i-PIDP: a new bone imaging agent.

This study was to investigate the preparation and biodistribution of (99m)Tc-labeled novel zoledronic acid derivative 1-hydroxy-2-(2-isopropyl-1H-imidazole-1-yl) ethylidene-1,1-bisphosphonic ((99m)Tc-i-PIDP) as a potential bone imaging agent. Satisfactory labeling results (radiochemical purity over 95%) were obtained when the amount of i-PIDP, Na(99m)TcO(4), and SnCl(2)·2H(2)O, were 5 mg, 37 MBq, and 100 µg, respectively, the pH value was between 4.0 and 6.0, and the labeling reaction continued for 30 min. The labeled complex was stable at least up to 6h in vitro. The biodistribution and pharmacokinetics studies in mice and single photon emission computed tomography (SPECT) bone scan in rabbit of (99m)Tc-i-PIDP were systematically studied. The results showed that the bone uptake is up to 9.63%ID/g at 60 min after injection of (99m)Tc-i-PIDP. The pharmacokinetic studies indicate that the data can be fitted to a two-compartment model with the equation of C=5.80e(-0.20t)+2.66e(-0.01t). A plain bone image was obtained at 1 h. All of the results suggested that (99m)Tc-i-PIDP is worthy of future investigation as a novel bone imaging agent.

Preparation and preclinical pharmacological study on a novel bone imaging agent (99m)Tc-EMIDP.

A novel zoledronic acid (ZL) derivative, 1-hydroxy-2-(2-ethyl-4-methyl-1H-imidazol-1-yl)ethane-1,1-diyldiphosphonic acid (EMIDP), was prepared and labeled with (99)(m)Tc successfully in a high labeling yield and good stability in vitro. The preclinical pharmacological properties of (99)(m)Tc-EMIDP were investigated and compared with (99)(m)Tc-MDP and (99)(m)Tc-ZL. The studies of biodistribution in mice and SPECT bone imaging of the rabbit suggest that (99)(m)Tc-EMIDP has highly selective uptake in the skeletal system and rapid clearance in the soft tissues. The present findings indicate that (99)(m)Tc-EMIDP holds great potential for bone scintigraphy.

Molecular imaging application of radioiodinated anti-EGFR human Fab to EGFR-overexpressing tumor xenografts.

BACKGROUND: Suitable diagnostics could identify patients who might benefit from targeted therapies. Molecular imaging is a promising method estimating the expression of specific molecules in vivo, and the goal of this study was to evaluate a radioiodinated anti-epidermal growth factor receptor (EGFR) human Fab as a molecular imaging agent for diagnosis. MATERIALS AND METHODS: Three human tumor cell lines representing tumors with different levels of EGFR expression were selected and their corresponding xenografts produced. (125)I was conjugated to a human anti-EGFR Fab that recognizes the native extracellular domain of EGFR evidenced by immunoprecipitation (IP) and fluorescence-activated cell sorting (FACS) assays. Single-photon-emission computed tomography (SPECT) imaging of (125)I-Fab being administered to nude mice bearing xenografts were obtained, and further analyzed by region of interest (ROI) assay. RESULTS: The (125)I-Fab was achieved successfully without losing its immunoreactivity. The scintigrams as well as ROI assay showed that (125)I-Fab was able to clearly quantitatively distinguish the different expression levels of EGFR in vivo. CONCLUSION: (125)I-Fab is a potential molecular imaging agent for clinical diagnosis of EGFR-overexpressing tumors.