Due to the specificity of radiopharmaceuticals for targeted α radionuclide therapy, such as radioactivity and radiation damage risk, it is necessary to estimate the internal radiation dose in preclinical evaluation to correctly evaluate the efficacy and safety of the drug, as well as in subsequent clinical studies. This review illustrates current research status of estimating internal radiation dose of targeted α radionuclide therapeutic radiopharmaceuticals based on preclinical studies, in order to add insights for understanding estimation of radiopharmaceuticals internal radiation dose and provide reference for the preclinical evaluation of radiopharmaceuticals.

Objective:To explore the clinicopathologic features differences between tall cell variant of papillary thyroid cancer (TCV-PTC) and PTC with tall cell features (PTC-TCF) and the factors influencing efficacy of 131I therapy in patients with TCV-PTC and PTC-TCF. Methods:A retrospective analysis was conducted on 84 patients (28 males, 56 females, age 43.5(35.0, 55.0) years) with pathologically confirmed TCV-PTC or PTC-TCF and who were treated with 131I therapy from January 2018 to June 2023 in the Department of Nuclear Medicine, the Affiliated Hospital of Qingdao University. The patients were divided into structural incomplete response (SIR) group and non-SIR group according to 131I treatment response. Data differences were analyzed by Wilcoxon rank sum test, Fisher exact test, or Mann-Whitney U test. Variables with P<0.1 were enrolled in logistic multivariate regression analysis. The ROC curve was used to obtain the cut-off value of stimulated thyroglobulin (sTg). Results:A total of 37 patients with non-SIR and 6 patients with SIR were found in TCV-PTC group ( n=43), and 33 non-SIR and 8 SIR cases were found in PTC-TCF group ( n=41). Univariate analysis revealed that sTg differed significantly between non-SIR patients and SIR patients in TCV-PTC group ( Z=-2.81, P=0.003), while no significant differences observed for sex, age, multifocality, capsular invasion, T stage, N stage, B-Raf proto-oncogene, serine/threonine-protein kinase (BRAF) V600E mutation, initial recurrence risk, number of metastatic lymph nodes, maximum tumor diameter ( Z values: from -0.74 to -0.11, all P>0.05). In TCV-PTC group, sTg also differed significantly between non-SIR patients and SIR patients ( Z=-4.40, P<0.001), while the other clinical factors above and the proportion of tall cells showed no significant difference ( Z values: from -1.90 to -0.22, all P>0.05). The logistic regression analysis confirmed sTg as an independent risk factor of SIR in both TCV-PTC group (odds ratio ( OR) = 25.156, 95% CI: 2.245-281.812, P=0.009) and PTC-TCF group ( OR=19.214, 95% CI: 2.537-145.502, P=0.004). The ROC curve indicated that the cut-off value of sTg for predicting SIR was 20.75μg/L in TCV-PTC group and 18.55μg/L in PTC-TCF group. Conclusions:sTg is the independent risk factor for predicting the poor prognosis of patients with TCV-PTC (sTg≥20.75μg/L) and PTC-TCF (sTg≥18.55μg/L). However, other clinical characteristics show no statistical difference between TCV-PTC group and PTC-TCF group, suggesting that the invasiveness of PTC-TCF may not be lower than that of TCV-PTC, which close attention should be paid to in clinical practice.

Due to the specificity of radiopharmaceuticals for targeted α radionuclide therapy, such as radioactivity and radiation damage risk, it is necessary to estimate the internal radiation dose in preclinical evaluation to correctly evaluate the efficacy and safety of the drug, as well as in subsequent clinical studies. This review illustrates current research status of estimating internal radiation dose of targeted α radionuclide therapeutic radiopharmaceuticals based on preclinical studies, in order to add insights for understanding estimation of radiopharmaceuticals internal radiation dose and provide reference for the preclinical evaluation of radiopharmaceuticals.

Objective:To explore the clinicopathologic features differences between tall cell variant of papillary thyroid cancer (TCV-PTC) and PTC with tall cell features (PTC-TCF) and the factors influencing efficacy of 131I therapy in patients with TCV-PTC and PTC-TCF. Methods:A retrospective analysis was conducted on 84 patients (28 males, 56 females, age 43.5(35.0, 55.0) years) with pathologically confirmed TCV-PTC or PTC-TCF and who were treated with 131I therapy from January 2018 to June 2023 in the Department of Nuclear Medicine, the Affiliated Hospital of Qingdao University. The patients were divided into structural incomplete response (SIR) group and non-SIR group according to 131I treatment response. Data differences were analyzed by Wilcoxon rank sum test, Fisher exact test, or Mann-Whitney U test. Variables with P<0.1 were enrolled in logistic multivariate regression analysis. The ROC curve was used to obtain the cut-off value of stimulated thyroglobulin (sTg). Results:A total of 37 patients with non-SIR and 6 patients with SIR were found in TCV-PTC group ( n=43), and 33 non-SIR and 8 SIR cases were found in PTC-TCF group ( n=41). Univariate analysis revealed that sTg differed significantly between non-SIR patients and SIR patients in TCV-PTC group ( Z=-2.81, P=0.003), while no significant differences observed for sex, age, multifocality, capsular invasion, T stage, N stage, B-Raf proto-oncogene, serine/threonine-protein kinase (BRAF) V600E mutation, initial recurrence risk, number of metastatic lymph nodes, maximum tumor diameter ( Z values: from -0.74 to -0.11, all P>0.05). In TCV-PTC group, sTg also differed significantly between non-SIR patients and SIR patients ( Z=-4.40, P<0.001), while the other clinical factors above and the proportion of tall cells showed no significant difference ( Z values: from -1.90 to -0.22, all P>0.05). The logistic regression analysis confirmed sTg as an independent risk factor of SIR in both TCV-PTC group (odds ratio ( OR) = 25.156, 95% CI: 2.245-281.812, P=0.009) and PTC-TCF group ( OR=19.214, 95% CI: 2.537-145.502, P=0.004). The ROC curve indicated that the cut-off value of sTg for predicting SIR was 20.75μg/L in TCV-PTC group and 18.55μg/L in PTC-TCF group. Conclusions:sTg is the independent risk factor for predicting the poor prognosis of patients with TCV-PTC (sTg≥20.75μg/L) and PTC-TCF (sTg≥18.55μg/L). However, other clinical characteristics show no statistical difference between TCV-PTC group and PTC-TCF group, suggesting that the invasiveness of PTC-TCF may not be lower than that of TCV-PTC, which close attention should be paid to in clinical practice.

Objective:To investigate the value of cellular immune status before initial 131I treatment for predicting treatment response in young and middle-aged patients with papillary thyroid cancer (PTC). Methods:From March 2018 to April 2019, 150 young and middle-aged patients with PTC (46 males, 104 females, age (40.0±9.8) years) who underwent total thyroidectomy and neck lymph node dissection in the Affiliated Hospital of Qingdao University were enrolled retrospectively. All patients underwent radioablation 1-2 months after operation, and the serum lymphocyte subsets (CD3 + , CD4 + , CD8 + , CD4/CD8) as well as natural killer (NK) cells were detected 1 d before the initial 131I treatment. Patients were divided into excellent response (ER) group and non-ER group according to the response of 6-12 months after 131I treatment. Clinicopathological characteristics, preablative stimulated thyroglobulin (psTg), initial 131I dose and lymphocyte subsets that might affect the response to 131I treatment were analyzed (independent-sample t test, Mann-Whitney U test, χ2 test, multiple logistic regression analysis). ROC curve analysis was used to evaluate the predictive value of significant factors for non-ER. Results:Of 150 patients, 84 cases were in ER group (56.00%), and 66 cases (44.00%) were in non-ER group. Age ( z=-2.86, P=0.004), M stage ( χ2=13.64, P<0.001), psTg ( z=-8.94, P<0.001), initial 131I dose ( z=-7.60, P<0.001), CD4 + ( t=2.50, P=0.014), CD4/CD8 ( z=-2.22, P=0.027) of the two groups were significantly different. Multivariate analysis showed that psTg (odds ratio ( OR)=1.27, 95% CI: 1.16-1.40, P<0.001) and CD4/CD8 ( OR=0.39, 95% CI: 0.15-0.99, P=0.048) were independent factors for predicting 131I treatment response. The cut-off values of psTg and CD4/CD8 for predicting non-ER were 6.78 μg/L and 1.67, respectively. Conclusions:Cellular immune status before initial 131I treatment may predict treatment response in young and middle-aged patients with PTC. It indicates non-ER response when Tg is higher than 6.78 μg/L and CD4/CD8 is lower than 1.67.

Objective:To investigate the efficacy and safety of anlotinib in distant metastatic radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC).Methods:Retrospective analysis was performed on 17 patients with distant metastatic RAIR-DTC (6 males, 11 females, age: 57.0(45.5, 63.0) years) from Affiliated Hospital of Qingdao University between October 2018 and February 2023, including 13 patients receiving first-line treatment and 4 patients receiving second-line treatment with anlotinib. The changes of serum thyroglobulin (Tg) during the treatment of anlotinib, the changes of maximum diameter of the target lesion at the last follow-up compared with the diameter at baseline, the imaging efficacy, and treatment-related adverse events were analyzed. The serological and imaging effects of the first-line treatment group and the second-line treatment group were compared. The Fisher exact test was used to analyze the differences between groups.Results:The follow-up time of 17 patients was 17.3(9.5, 21.4) months, and the objective response rate (ORR) and disease control rate (DCR) were 7/17 and 16/17, respectively. There were no significant differences of ORR (6/13 vs 1/4; P=0.603) and DCR (13/13 vs 3/4; P=0.235) between the first-line and second-line treatment groups. The change rates of serum Tg at 3, 6 weeks and the last follow-up were -30.2%(-61.2%, -15.5%), -64.8%(-90.6%, -32.3%), and -85.8%(-96.1%, -50.7%), respectively. At the last follow-up, the change rate of maximum diameter of target lesions was -20.0%(-45.0%, -5.2%). The incidence of treatment-related adverse reactions was 14/17, and 2 patients (2/17) had grade 3 or above adverse reactions. Conclusion:Anlotinib shows superior efficacy with tolerable toxicity in the first-line treatment of distant metastatic RAIR-DTC, and hopefully plays an important role in second-line treatment for RAIR-DTC resistant to sorafenib.

Objective:To investigate the preoperative diagnostic value of 99Tc m-methoxyisobutylisonitrile (MIBI) planar imaging and SPECT/CT imaging for primary hyperparathyroidism (PHPT), and analyze the relevant factors affecting the imaging results. Methods:From June 2016 to September 2019, a total of 62 patients (15 males, 47 females, age range: 27-80 years) confirmed as PHPT by postsurgical pathology in Affiliated Hospital of Qingdao University were retrospectively enrolled. The diagnostic efficacies of 99Tc m-MIBI planar imaging and SPECT/CT imaging were compared using χ2 test. The differences of preoperative serum parathyroid hormone (PTH), Ca and the maximum diameter of lesion between the positive and negative groups of planar imaging were analyzed using independent-sample t test and Mann-Whitney U test. The region of interest (ROI) method was applied to calculate the uptake ratio of lesions to normal tissues at the early phase (T/Ne) and delayed phase (T/Nd) in positive cases of planar imaging. Pearson or Spearman correlation analysis was used to evaluate the correlation of T/Ne, T/Nd with preoperative serum PTH, Ca and the maximum diameter of lesion. The receiver operating characteristic (ROC) curves of preoperative serum PTH, Ca and positive planar imaging were drawn and the cut-off values were obtained. Results:The sensitivity of planar imaging and SPECT/CT imaging was 69.35%(43/62) and 87.10%(54/62) respectively ( χ2=5.729, P=0.017). The preoperative serum PTH, Ca levels and the maximum diameter of lesion in patients with positive planar imaging (253.32(107.00, 331.70) ng/L, 2.78(2.51, 2.87) mmol/L, (2.01±0.88) mm) were higher than those with negative planar imaging ((111.86±44.29) ng/L, (2.59±0.21) mmol/L, (1.42±0.55) mm; z values: -2.802, -1.978, t=3.300, all P<0.05). T/Ne was positively correlated with preoperative serum PTH ( rs=0.511, P<0.001) and the maximum diameter of lesion ( r=0.381, P=0.012), and T/Nd was positively correlated with preoperative serum PTH ( rs=0.538, P<0.001), Ca ( rs=0.348, P=0.022) and the maximum diameter of lesion ( r=0.463, P=0.002). The area under the ROC curve between preoperative serum PTH, Ca and planar imaging was 0.725 and 0.646, respectively. Preoperative serum PTH had a better predictive value with the optimal cut-off value of 150.4 ng/L. Conclusions:Preoperative serum PTH, Ca and the maximum diameter of lesion are positively correlated with 99Tc m-MIBI uptake in PHPT patients with positive planar imaging results. When preoperative serum PTH is lower than 150.4 ng/L, planar imaging is prone to false negative. SPECT/CT imaging has a significant value in preoperative diagnosis and the combination of PTH and CT can improve the positive rate.

Objective:To investigate the association of muscle mass loss with atherosclerosis in elderly patients with type 2 diabetes mellitus(T2DM).Methods:A total of 322 patients with T2DM aged≥60 years old were divided into muscle mass loss group( n=152) and non-muscle mass loss group( n=170) according to their appendicular skeletal muscle mass index(ASMI). All participants underwent physical examination, dual-energy X-ray absorptiometry check, carotid and lower extremity ultrasound, as well as laboratory tests. Results:Among 322 patients, 49(15.22%) patients were suffered from sarcopenia and 152(47.2%) patients with reduced muscle mass. The carotid and lower extremity atherosclerosis grades in the muscle mass loss group were significantly higher than those in the non-muscle mass loss group( P<0.05), with lower body mass index(BMI), T-score, ASMI, uric acid, and homeostasis model assessment of insulin resistance index( P<0.05). Multivariate logistic regression analysis showed that carotid atherosclerosis and lower extremity atherosclerosis were risk factors for muscle mass loss while BMI and 25-(OH)D 3 were protective factors for muscle mass loss. There existed a consistency in carotid atherosclerosis grade and lower extremity atherosclerosis grade of elderly patients with T2DM( P<0.01). Conclusion:Atherosclerosis has a predictive value for early sarcopenia in elderly patients with T2DM.

Objective: To investigate the response to ¹³¹I therapy and to explore the influence factors in postoperative differentiated thyroid carcinoma (DTC) patients with negative preablative stimulated thyroglobulin (psTg) and iodine-positive lymph node after the first radioablation. Methods: From May 2016 to October 2018, 108 DTC patients (28 males, 80 females, age: (45.7±10.4) years) with negative psTg who underwent ¹³¹I treatment for the first time in the Affiliated Hospital of Qingdao University were retrospectively enrolled. All patients had iodine-positive lymph nodes, which were showed by SPECT/CT imaging 5-6 d after ¹³¹I treatment. The treatment response was evaluated at 6-24 month after ¹³¹I treatment. Patients were divided into excellent response (ER) group and non-excellent response (non-ER) group according to the response to the first ¹³¹I treatment. Independent-sample t test, χ² test and Mann-Whitney U test were used to analyze differences of factors (e.g. age, gender, extraglandular infiltration) between the 2 groups, and then multivariate logistic regression was performed to find the influence factors for treatment response. The receiver operating characteristic (ROC) curve was employed to evaluate the predictive value of the iodine-positive lymph node size in ¹³¹I treatment response. Results: A total of 82 patients (75.93%, 82/108) achieved ER, and 26 (24.07%, 26/108) was non-ER patients. There were significant differences in age (t=-2.540, P=0.016), extraglandular infiltration (χ²=5.764, P=0.016), T stage (χ²=19.857, P<0.001), N stage (χ²=14.145, P=0.001), risk stratification of recurrence (χ²=11.487, P=0.003), ultrasound results before ¹³¹I treatment (χ²=44.819, P<0.001), dose of the first ¹³¹I treatment (U=780.0, P=0.018), size (long diameter) of iodine-positive lymph node (U=184.0, P<0.001), and psTg level (U=776.0, P=0.037) between ER and non-ER groups. Multivariate logistic regression showed that age, size of iodine-positive lymph node and ultrasound results before ¹³¹I treatment were closely related to ¹³¹I treatment response. The odds ratio (OR) values (95% CI) were 1.123 (1.025-1.231), 4.275 (1.893-9.653) and 260.86 (8.123-8 376.764), respectively. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value for non-ER were 100%(26/26), 70.73%(58/82), 77.78%(84/108), 52.00%(26/50) and 100%(58/58) respectively when the cut-off value of iodine-positive lymph node size was 5.5 mm. Conclusion The response of some DTC patients with negative psTg and iodine-positive lymph node after the first radioablation were non-ER. Age, ultrasound results before ¹³¹I treatment and size of iodine-positive lymph node are sensitive indicators for predicting clinical outcome in DTC patients with negative psTg and iodine-positive lymph node after the first radioablation.

Objective To explore the relationship between the stimulated thyroglobulin ( sTg) and site, number and diameter of metastatic lesions in patients with differentiated thyroid carcinoma (DTC) before the first 131 I treatment, and to evaluate the predictive value of sTg for different metastatic sites. Methods A total of 567 DTC patients (179 males, 388 females; age: (45.3±12.3) years) who received the first 131Ⅰ treatment between January 2012 and June 2017 were included. Thyroglobulin antibody (TgAb), sTg and thyroid stimulating hormone ( TSH) were determined within 1 week before 131 I treatment. Metastases were detected by ultrasonography, CT or 18 F-fluorodeoxyglucose ( FDG ) PET/CT, 131 I whole-body scan, SPECT/CT imaging and pathology. sTg levels of patients with different metastatic sites and different metasta-sis numbers or lesion diameters were compared ( Kruskal-Wallis H test) . Spearman correlation analysis was performed on the number, diameter and sTg level of metastases. The receiver operating characteristic ( ROC) curve was used to explore the predictive value of sTg before the first 131 I treatment for DTC metasta-sis. Results The median values of sTg in the bone, lung, lymph node metastases groups and non-metasta-sis group were 500.00, 104.40, 27.45, 2.39μg/L, respectively, and there were significant differences, ex-cept for bone and lung metastases groups ( H range: -294.605 to 175.162, all P<0.05) . The sTg levels of lung metastasis group and lymph node metastasis group were both decreased by the order of metastasis num- bers (≥3, =2, =1;H range:-57.887 to 48.763, all P<0.05) . As to the diameter of metastases, the sTg levels of >2.0 cm, 1.1-2.0 cm, and≤1.0 cm subgroups in the lung metastasis group and lymph node me-tastasis group were also decreased in order ( H range: -69.935 to 61.043, all P<0.05) . Spearman correla-tion analysis showed that the number ( rs=0.568, 0.606) and diameter ( rs=0.806, 0.664) of the metasta-ses in the lung and lymph node metastases group were positively correlated with sTg (all P<0.05). Areas under ROC curves for sTg to predict bone, lung and lymph node metastasis were 0.935, 0.843 and 0.791 re-spectively. The threshold values were 197. 65, 23. 21 and 10. 96 μg/L respectively. The sensitivities and the specificities were 91.70％, 79.60％, 67.20％ and 97.20％, 80.80％, 82.70％ respectively. Conclusions Tg level before the first 131 I treatment has a certain predictive value for the metastasis, metastatic site and num-ber or diameter in DTC patients.