Prediction of risk for symptomatic sialadenitis by post-therapeutic dual 131I scintigraphy in patients with differentiated thyroid cancer

Objective

The aim of this study is to predict the risk of symptomatic sialadenitis after ¹³¹I therapy using the early (third day post-therapy) and delayed (fifth or sixth day post-therapy) post-therapeutic ¹³¹I scintigraphy images in patients with differentiated thyroid cancer (DTC).

Methods

Included in the study were 112 patients with DTC who underwent early and delayed ¹³¹I scans after ¹³¹I treatment. All patients had normal salivary gland function on salivary scintigraphy performed in the week before the ¹³¹I treatment. Scintigraphy images were visually analyzed and the salivary gland-to-background uptake ratio (SUR) and percent change of the SUR between early and delayed scans were calculated. Calculation of effective half-life and absorbed dose in the salivary glands was performed based on the MIRD schema.

Results

Of 112 patients, symptomatic sialadenitis was diagnosed in 46 patients (41 %). Of these 46 patients, 83 % (38 patients) had persistent ¹³¹I uptake in the salivary glands on both early and delayed scans. Among 55 patients with persistent ¹³¹I uptake in the salivary glands, 69 % experienced symptomatic sialadenitis, while only 14 % of the other 57 patients experienced symptomatic sialadenitis (p < 0.0001). On the early ¹³¹I scintigraphy, SURs of bilateral parotid glands on early scan in patients with symptomatic sialadenitis were significantly higher than in other patients (p = 0.001 for right and p = 0.004 for left). Further, patients with symptomatic sialadenitis had a higher decreasing rate of the SUR and shorter effective half-life of ¹³¹I in bilateral parotid glands than other patients. Using visual analysis and SURs of right and left parotid glands on early ¹³¹I scan as parameters, the sensitivities for predicting symptomatic sialadenitis were 83, 80, and 93 %, respectively. The mean values of effective half-life and absorbed dose in the parotid and submandibular glands were 20.8 ± 6.3 h and 2.7 ± 0.8 Gy, and 22.1 ± 7.9 h and 2.8 ± 1.1 Gy, respectively.

Conclusions

Symptomatic sialadenitis can be predicted by post-therapeutic ¹³¹I scintigraphy with high sensitivity. Post-therapeutic ¹³¹I scintigraphy could provide effective information on the risk of symptomatic sialadenitis in DTC patients who underwent ¹³¹I treatment.     

Value of the first serum thyroglobulin level after total thyroidectomy for the diagnosis of metastases from differentiated thyroid carcinoma

The aim of this study was to evaluate the diagnostic significance of the first serum thyroglobulin (Tg) measurement, performed 40 days after total thyroidectomy for differentiated thyroid carcinoma and prior to the ablation of residual thyroid tissue by means of iodine-131 therapy. In a retrospective study we examined 334 consecutive patients followed up for 4–16 years by means of regular Tg measurements, ¹³¹I whole-body scans (WBS) and other diagnostic techniques, if necessary. In 79 patients metastases were discovered (32 lymph node and 47 distant metastases) within 18 months following thyroidectomy. Mean values of first Tg were significantly higher in patients with than in patients without metastases (258.9±310.6 vs 15.9±19.6 ng/ml; P<0.0001). Receiver operating characteristic (ROC) curve analysis of data revealed that for first Tg values higher than 69.7 ng/ml, the positive predictive value for the presence of metastases exceeded 90%. No statistically significant correlation was found between first Tg value and either thyroid-stimulating hormone (TSH) value or percentage of ¹³¹I uptake by residual thyroid tissue. No other parameter (age, histological type, site of metastases, ¹³¹I uptake by metastases) was significantly related to the first Tg value. We conclude that the first Tg measurement after total thyroidectomy provides a useful early diagnostic indication of metastatic disease in spite of the presence of a post-surgical thyroid remnant, and that this holds true regardless of the TSH value and WBS result. This early information is of clinical relevance for patient follow-up. Received 26 October 1998 and in revised form 12 June 1999     

Iodine Uptake Patterns on Post-ablation Whole Body Scans are Related to Elevated Serum Thyroglobulin Levels After Radioactive Iodine Therapy in Patients with Papillary Thyroid Carcinoma

Purpose

Serum thyroglobulin (Tg) level is frequently elevated shortly after radioactive iodine (RAI) ablation therapy. The authors studied the relationship between the elevation of serum Tg after RAI therapy and iodine uptake pattern on post-ablation whole body scans (RxWBSs) in patients with papillary thyroid carcinoma (PTC).

Materials and Methods

The study subjects were patients with PTC that had undergone first RAI therapy with thyroid hormone withdrawal after total thyroidectomy. Patients with a high level of serum anti-Tg antibody (TgAb, ≥ 60 U/mL), possible regional or distant metastasis as determined by pre-ablation or post-ablation studies, and negative iodine uptake of the anterior neck on RxWBS were excluded. Serum Tg was checked twice, that is, 7 days after (post-ablation Tg) and on the day of RAI therapy (pre-ablation Tg). Ratio of pre-ablation Tg to post-ablation Tg (Tg ratio) was used to assess changes in serum Tg levels after RAI therapy. Patients were classified into two groups according to the presence of midline uptake above the thyroidectomy bed on RxWBS (negative (group 1) or positive (group 2) midline uptake). Variables were subjected to analysis to identify differences between the two groups.

Results

Two hundred and fifty patients were enrolled in this study; 101 in group 1 and 149 in group 2. Based on univariate analysis, post-ablation Tg (8.12?±?11.05 vs. 34.12?±?54.31; P?<?0.001) and Tg ratio (7.81?±?8.98 vs. 20.01?±?19.84; P?<?0.001) were significantly higher in group 2. On the other hand, gender, tumor (T) stage, lymph node (N) stage, size, multiplicity or bilaterality of primary tumor, dose of ¹³¹I, serum TgAb and thyroid-stimulating hormone (TSH) level (before or after RAI therapy) were not significantly different in the two groups. Variables with P values of < 0.25 by univariate analysis were subjected to multivariate analysis, which showed post-ablation Tg (OR 1.060, 95 % CI?=?1.028–1.092; P?<?0.001) and Tg ratio (OR 1.059, 95 % CI?=?1.028–1.092; P?=?0.001) were significantly higher in group 2.

Conclusion

Serum Tg level after RAI therapy was significantly higher in patients with midline uptake on RxWBS, compared with patients without midline uptake on RxWBS. Further investigations are needed to reveal the correlation between serum Tg elevation and clinical outcome according to the presence of midline uptake.

     

Evaluation of an anti-p185 (scFv-CH2-CH3)2 fragment following radioiodination using two different residualizing labels: SGMIB and IB-Mal-d-GEEEK

IntroductionA 105-kDa double mutant single-chain Fv-Fc fragment (scFv-Fc DM) derived from the anti-p185^HER2 hu4D5v8 antibody (trastuzumab; Herceptin) has been described recently. The goal of this study was to investigate whether improved tumor targeting could be achieved with this fragment through the use of residualizing radioiodination methods.MethodsThe scFv-Fc DM fragment was radioiodinated using N-succinimidyl 4-guanidinomethyl 3-[¹³¹I]iodobenzoate ([¹³¹I]SGMIB) and N^?-(3-[¹³¹I]iodobenzoyl)-Lys⁵-N^α- maleimido-Gly¹-GEEEK ([¹³¹I]IB-Mal-d-GEEEK), two residualizing radioiodination agents that have been used successfully with intact antibodies. Paired-label internalization assays of the labeled fragments were performed in vitro using MCF7 human breast cancer cells transfected to express HER2 (MCF7-HER2); comparisons were made to scFv-Fc DM directly radioiodinated using Iodogen. The tissue distribution of the scFv-Fc DM labeled with [¹²⁵I]IB-Mal-d-GEEEK and [¹³¹I]SGMIB was compared in athymic mice bearing MCF7-HER2 xenografts.ResultsThe scFv-Fc DM fragment was labeled with [¹³¹I]SGMIB and [¹³¹I]IB-Mal-d-GEEEK in conjugation yields of 53% and 25%, respectively, with preservation of immunoreactivity for HER2. Internalization assays indicated that labeling via SGMIB resulted in a 1.6- to 3.5-fold higher (P<.05) retention of radioactivity, compared to that from the directly labeled fragment, in HER2-expressing cells during a 24-h observation period. Likewise, the amount of radioactivity retained in cells from the IB-Mal-d-GEEEK-labeled fragment was 1.4- to 3.3-fold higher (P<.05). Tumor uptake of radioiodine activity in athymic mice bearing MCF7-HER2 xenografts in vivo was significantly higher for the [¹²⁵I]IB-Mal-d-GEEEK-labeled scFv-Fc DM fragment compared with that of the [¹³¹I]SGMIB-labeled fragment, particularly at later time points. The uptake of ¹²⁵I was threefold (3.6±1.1 %ID/g vs. 1.2±0.4 %ID/g) and fourfold (3.1±1.7 %ID/g vs. 0.8±0.4 %ID/g) higher than that for ¹³¹I at 24 and 48 h, respectively. However, the [¹²⁵I]IB-Mal-d-GEEEK-labeled scFv-Fc DM fragment also exhibited considerably higher levels of radioiodine activity in liver, spleen and kidney.ConclusionsThe overall results further demonstrate the potential utility of these two prosthetic groups for the radiohalogenation of internalizing monoclonal antibodies and their fragments. Specifically, the trastuzumab-derived double mutant fragment in combination with these residualizing agents warrants further evaluation for imaging and possibly treatment of HER2 expressing malignancies.     

Lung uptake on I-131 therapy and short-term outcome in patients with lung metastasis from differentiated thyroid cancer

Objective

It is sometimes difficult to assess I-131 lung uptake at the initial I-131 therapy because of strong artifacts from I-131 uptake in the thyroid bed. The aim of this study was to analyze the lung uptake at the second I-131 therapy for lung metastasis in patients who did not have lung uptake at the initial therapy from differentiated thyroid carcinoma (DTC). Then, we also analyzed the relationship between the initial lung uptake and short-term outcome after I-131 therapies.

Methods

This study included 62 DTC patients with lung metastasis. The patients were classified into 2 groups according to the lung uptake at the initial I-131 therapy such as patients with lung uptake (positive uptake group n = 31) and those without lung uptake (negative uptake group n = 31). The lung uptake was analyzed at the second therapy in both groups. The short-term outcome was also analyzed based on the CT findings of lung metastasis size and serum thyroglobulin level between the two groups.

Results

The positive uptake group showed positive lung uptake at the second therapy in 23 patients (74 %), whereas none of negative uptake group showed any lung uptake at the second therapy (P < 0.01). The positive uptake group significantly decreased in the size of lung metastasis from the initial therapy to the second therapy (20.0 ± 11.7 to 16.6 ± 9.6 mm, P < 0.01) with further decrease after the second therapy (P < 0.05). The serum thyroglobulin level was also significantly decreased from the initial therapy to the second therapy (4348 ± 7011 to 2931 ± 4484 ng/ml, P < 0.05). In contrast, the negative uptake group significantly increased in the size of lung metastasis from the initial therapy to the second therapy (17.3 ± 12.2 to 19.9 ± 14.3 mm, P < 0.01) with further increase after the second therapy (P < 0.01).

Conclusion

No patients without lung uptake at the initial I-131 therapy showed lung uptake at the second therapy, or showed treatment effect. Therefore, second I-131 therapy for these patients with initially negative lung uptake should be considered cautiously.     

1-23I-MIBG thyroid uptake: Implications for MIBG imaging of the heart

Background

123I-MIBG has been widely used in patients with heart failure and neurological disorders. The patients are pre-treated with Lugol’s oral solution or potassium perchlorate to prevent thyroid uptake of unlabeled 123I to limit the thyroid radiation exposure. However, despite the inhibition of the iodide pump, the thyroid is frequently visualized. The aim of this study was to study the pattern of thyroid uptake.

Methods

We reviewed the 123I-MIBG images of 57 patients studied in three different centers in Italy for cardiac (n = 42) or neurological (n = 15) indications. They were imaged at 15 minutes and 4 hours after injection and in all patients, the thyroid was included in the imaging field of view. In 2 of the 3 centers, the patients were pre-treated with Lugol’s oral solution and/or potassium perchlorate (group 1) but in the third center, they were not (group 2). The following imaging parameters were evaluated: heart-to-mediastinum ratio (H/M), thyroid-to-mediastinum ratio (T/M) at 4 hours, and tracer wash out from the heart (HWO) and from the thyroid (TWO).

Results

In the cardiac patients, the HWO was 22.98 ± 7.16% and TWO was 11.4 ± 11.86% (P < .0001). The TWO was 12.2 ± 13.1% in group 1 and 10.05 ± 8.97% in group 2 (P = NS). In the neurological patients the HWO was 26 ± 8.1% and the TWO was 20.32 ± 6.41 (P < .05). The difference in TWO was statistically significant (P < .01) between cardiac and neurological patients, whereas the HWO was not. The 4-hour H/M was 1.49 ± 0.23 in cardiac patients vs 1.4 ± 0.39 in neurological patients (P = NS). The 4-hour T/M was 1.33 ± 0.3 in cardiac patients vs 1.15 ± 0.13 in neurological patients (P < 0.05).

Conclusion

The thyroid visualization in MIBG imaging is likely an expression of thyroid sympathetic innervation. The differences in TWO and T/M ratio in cardiac and neurological patients probably express differences in thyroid dopaminergic receptors. Thus, pre-treatment with potassium perchlorate or Lugol’s solution may not be justified in patients undergoing 123I-MIBG imaging in whom the risk of side effects due to pre-treatment could be higher than the risk due to thyroid radiation exposure.

     

Recovery of 131I from alkaline solution of n-irradiated tellurium target using a tiny Dowex-1 column

A simple and inexpensive ion-exchange chromatography method for the separation of medically useful no-carrier-added (nca) iodine radionuclides from bulk amounts of irradiated tellurium dioxide (TeO₂) target was developed and tested using ¹³¹I. The radiochemical separation was performed using a very small Dowex-1×8 ion-exchange column. The overall radiochemical yield for the complete separation of ¹³¹I was 92±1.8 (standard deviation) % (n=8). The separated nca ¹³¹I was of high, ～99%, radionuclidic and radiochemical purity and did not contain detectable amounts of the target material. This method may be adopted for the radiochemical separation of other different iodine radionuclides produced from tellurium matrices through cyclotron as well as reactor irradiation.     

Discrepant uptake of the radiolabeled norepinephrine analogues hydroxyephedrine (HED) and metaiodobenzylguanidine (MIBG) in rat hearts

Purpose

¹¹C-Hydroxyephedrine (HED) and radioiodinated metaiodobenzylguanidine (¹²³I/¹³¹I-MIBG) are catecholamine analogue tracers for sympathetic nerve positron emission tomography/single photon emission computed tomography (PET/SPECT) imaging. In contrast to humans, rat hearts demonstrate high nonneural catecholamine uptake-2 in addition to neural uptake-1, the contributions of which to tracer accumulation are not fully elucidated.

Methods

Wistar rats were studied using the following pretreatments: uptake-1 blockade with desipramine 2 mg/kg IV, both uptake-1 and -2 blockade with phenoxybenzamine 50 mg/kg IV, or control with saline IV. HED or ¹²³I-MIBG was injected 10 min after pretreatment, and rats were sacrificed 10 min later. Heart to blood tissue count ratio (H/B ratio) was obtained using a gamma counter. To determine regional tracer uptake, dual-tracer autoradiography was performed with HED and ¹³¹I-MIBG in Wistar rats with chronic infarction by transient coronary occlusion and reperfusion and in healthy control rats. Local tracer distributions were analyzed, and the infarcted rats’ local tracer distributions were compared with histology.

Results

The H/B ratios in control hearts were 34.4?±?1.7 and 25.5?±?2.1 for HED and ¹²³I-MIBG, respectively. Desipramine led to a significant decrease in HED (3.2?±?0.5, p?<?0.0001), while there was no change in ¹²³I-MIBG (25.5?±?6.4, p?=?n.s.). Phenoxybenzamine led to a significant decrease in both HED and ¹²³I-MIBG (3.5?±?0.02, 4.3?±?0.7, p?<?0.0001). Only HED showed a subepicardium-subendocardium gradient in healthy control hearts which is consistent with physiological innervation, while ¹³¹I-MIBG was evenly distributed throughout the myocardium. ¹³¹I-MIBG uptake defect closely matched the scar area determined by histology [3.8?±?2.3 % (¹³¹I-MIBG defect) vs 4.0?±?2.4 % (scar)]. However, the scar area was clearly exceeded by the HED uptake defect (9.1?±?2.2 %, p?<?0.001).

Conclusion

HED uptake showed high specificity to neural uptake-1 in rat hearts. On the other hand, ¹²³I/¹³¹I-MIBG demonstrated distinct characters of regional tracer distribution and uptake mechanism that are compatible with significant contribution of nonneural uptake-2.     

Clinical evaluation of no-carrier-added meta-[123I]iodobenzylguanidine for myocardial scintigraphy

In clinical and research studies, images obtained using carrier-added meta-[¹²³I]iodobenzylguanidine (c.a. [¹²³I]MIBG) have shown quite variable quality, with varying levels of uptake in lung, liver and mediastinum; this is a significant problem for quantification of the myocardial uptake by means of region ratios. First experimental and preliminary human data in respect of no-carrier-added (n.c.a.) [¹²³I]MIBG are indicative of improved imaging quality. The aim of the present study was to evaluate the clinical value of myocardial scintigraphy with n.c.a. [¹²³I]MIBG in patients with tachyarrhythmias. The study population comprised 24 patients with tachyarrhythmogenic diseases routinely studied by cardiac single-photon emission tomography (SPET) with [¹²³I]MIBG. Twelve of the 24 patients were studied with c.a. [¹²³I]MIBG (seven females and five males; mean age 42±13 years, range 20–60 years), whereas the other 12 were studied with n.c.a. [¹²³I]MIBG (ten females, two males; mean age 41±11 years, range 18–60 years, P=NS). For quantification of the specific uptake in the different organs, count ratios were calculated on SPET images acquired 4 h p.i. Visual analysis of all [¹²³I]MIBG scans showed improved image quality (improved contrast between heart and neighbouring organs) in n.c.a. studies as compared with c.a. studies. A significantly higher heart/left atrial blood ratio was found in the n.c.a. studies as compared with the c.a. studies (10.3±3.2 vs 5.3±1.3, P=0.0003); furthermore, significantly higher heart/lung and heart/liver ratios (2.5±0.6 vs 1.5±0.3, P=0.0002, and 0.8±0.2 vs 0.6±0.1, P=0.0006, respectively) were obtained in the c.a. studies, whereas lung/left atrial blood and liver/left atrial blood ratios showed no significant differences (4.2±1.3 vs 3.6±1.1, P=0.39, and 13.7±5.2 vs 9.6±2.2, P=0.21, respectively). In conclusion, the use of n.c.a. [¹²³I]MIBG yields a significantly higher myocardial uptake associated with improvement in contrast between the heart and neighbouring organs and is therefore superior to the commercially available c.a. [¹²³I]MIBG for use in clinical and research studies of the myocardial presynaptic sympathetic nervous system. Furthermore, our data indicate that for quantification the use of a left atrial blood reference region of interest, which is only available on SPET studies, is to be recommended. Received 22 September and in revised form 2 November 1999     

Myocardial damage assessed by indium-1 11-antimyosin: correlation with persistent enteroviral ribonucleic acid in dilated cardiomyopathy

The persistence of enteroviral ribonucleic acid (RNA) in the myocardium has been implicated as a pathogenetic factor in idiopathic dilated cardiomyopathy. Enteroviral persistence may lead to myocardial cell membrane damage, resulting in increased uptake of antimyosin antibodies. To further evaluate this hypothesis, a direct comparison of myocardial antimyosin uptake with the presence of enteroviral RNA was performed in ten patients (one female, nine male; 53±8 years) with chronic dilated cardiomyopathy. Planar antimyosin images were obtained 48 h after the injection of indium-111-labelled antimyosin Fab. Using a region of interest technique, the heart to lung uptake ratio (HLR) was calculated as a semiquantitative parameter of myocardial tracer uptake. Cardiac catheterization was performed to assess left ventricular function and to obtain myocardial biopsy samples. In the biopsy samples, gene amplification by polymerase chain reaction (PCR) was used to specifically detect enteroviral RNA. In the ten patients, the left ventricular ejection fraction was 39%±11% and the end-diastolic volume 131±46 ml/m². The HLR was 1.72±0.21 and showed no correlation with functional parameters. In two patients with a positive PCR consistent with persisting enteroviral RNA, the HLR was not higher than that in eight patients with a negative PCR (1.46±0.18 vs 1.78±0.18, respectively). These results suggest that increased uptake of¹¹¹In-antimyosin in chronic idiopathic dilated cardiomyopathy cannot be explained by pure persistence of enteroviral RNA. Other pathogenetic factors such as myocardial autoantibodies or microvascular spasm may be responsible for myocyte membrane damage detected by antimyosin.     

N-Succinimidyl guanidinomethyl iodobenzoate protein radiohalogenation agents: Influence of isomeric substitution on radiolabeling and target cell residualization

IntroductionN-succinimidyl 4-guanidinomethyl-3-[^⁎I]iodobenzoate ([^⁎I]SGMIB) has shown promise for the radioiodination of monoclonal antibodies (mAbs) and other proteins that undergo extensive internalization after receptor binding, enhancing tumor targeting compared to direct electrophilic radioiodination. However, radiochemical yields for [¹³¹I]SGMIB synthesis are low, which we hypothesize is due to steric hindrance from the Boc-protected guanidinomethyl group ortho to the tin moiety. To overcome this, we developed the isomeric compound, N-succinimidyl 3-guanidinomethyl-5-[¹³¹I]iodobenzoate (iso-[¹³¹I]SGMIB) wherein this bulky group was moved from ortho to meta position.MethodsBoc₂-iso-SGMIB standard and its tin precursor, N-succinimidyl 3-((1,2-bis(tert-butoxycarbonyl)guanidino)methyl)-5-(trimethylstannyl)benzoate (Boc₂-iso-SGMTB), were synthesized using two disparate routes, and iso-[*I]SGMIB synthesized from the tin precursor. Two HER2-targeted vectors — trastuzumab (Tras) and a nanobody 5 F7 (Nb) — were labeled using iso-[^⁎I]SGMIB and [^⁎I]SGMIB. Paired-label internalization assays in vitro with both proteins, and biodistribution in vivo with trastuzumab, labeled using the two isomeric prosthetic agents were performed.ResultsWhen the reactions were performed under identical conditions, radioiodination yields for the synthesis of Boc₂-iso-[¹³¹I]SGMIB were significantly higher than those for Boc₂-[¹³¹I]SGMIB (70.7 ± 2.0% vs 56.5 ± 5.5%). With both Nb and trastuzumab, conjugation efficiency also was higher with iso-[¹³¹I]SGMIB than with [¹³¹I]SGMIB (Nb, 33.1 ± 7.1% vs 28.9 ± 13.0%; Tras, 45.1 ± 4.5% vs 34.8 ± 10.3%); however, the differences were not statistically significant. Internalization assays performed on BT474 cells with 5 F7 Nb indicated similar residualizing capacity over 6 h; however, at 24 h, radioactivity retained intracellularly for iso-[¹³¹I]SGMIB-Nb was lower than for [¹²⁵I]SGMIB-Nb (46.4 ± 1.3% vs 56.5 ± 2.5%); similar results were obtained using Tras. Likewise, a paired-label biodistribution of Tras labeled using iso-[¹²⁵I]SGMIB and [¹³¹I]SGMIB indicated an up to 22% tumor uptake advantage at later time points for [¹³¹I]SGMIB-Tras.ConclusionGiven the higher labeling efficiency obtained with iso-SGMIB, this residualizing agent might be of value for use with shorter half-life radiohalogens.     

131I标记纳米脂质体靶向治疗结肠癌的实验研究

目的 研究¹³¹I-antiEGFR-BSA-PCL对LS180细胞结肠癌裸鼠移植瘤内照射的治疗效果。方法 构建抗表皮生长因子受体(EGFR)标记的纳米脂质体及EGFR靶向性。通过荧光共聚焦显微镜、细胞摄碘实验观察纳米载体的靶向性及LS180细胞对其摄取情况。将裸鼠40只按随机数字表法分为4组,通过瘤体内注射的方式向移植瘤内分别注射74 MBq (740 MBq/ml) ¹³¹I-antiEGFR-BSA-PCL、¹³¹I-BSA-PCL、¹³¹I及相同体积的生理盐水。通过研究裸鼠体重、肿瘤体积、SPECT显像及组织病理学方法,观察纳米脂质体的抑瘤效果。结果 共聚焦实验显示,与BSA-PCL组相比,antiEGFR-BSA-PCL组细胞内绿色荧光较明显,其介导的胞吞效应显著。摄碘率实验中,LS180细胞对¹³¹I-antiEGFR-BSA-PCL的摄取率明显高于¹³¹I-BSA-PCL(t=2.77~5.40,P<0.01)。¹³¹I-antiEGFR-BSA-PCL组与¹³¹I-BSA-PCL组裸鼠肿瘤增殖均较慢,二者差异无统计学意义(P>0.05)。给药后72 h,¹³¹I-antiEGFR-BSA-PCL与¹³¹I-BSA-PCL的肿瘤摄取率分别为(21.61±1.01)和(20.58±0.65)% ID/g,均明显高于¹³¹I组(t=9.36、8.69,P<0.01)。SPECT显像显示纳米脂质体主要特异性积聚在肿瘤区。结论 ¹³¹I-antiEGFR-BSA-PCL对LS180结肠癌裸鼠移植瘤有明显的抑制作用。     

Blood flow, flow reserve, and glucose utilization in viable and nonviable myocardium in patients with ischemic cardiomyopathy

Purpose

The aim of the study was to determine whether glucose uptake in viable myocardium of ischemic cardiomyopathy patients depends on rest myocardial blood flow (MBF) and the residual myocardial flow reserve (MFR).

Methods

Thirty-six patients with ischemic cardiomyopathy (left ventricular ejection fraction 25?±?10 %) were studied with ¹³N-ammonia and ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET). Twenty age-matched normals served as controls. Regional MBF was determined at rest and during dipyridamole hyperemia and regional FDG extraction was estimated from regional FDG to ¹³N-ammonia activity ratios.

Results

Rest MBF was reduced in viable (0.42?±?0.18 ml/min per g) and nonviable regions (0.32?±?0.09 ml/min per g) relative to remote regions (0.68?±?0.23 ml/min per g, p?<?0.001) and to normals (0.63?±?0.13 ml/min per g). Dipyridamole raised MBFs in controls, remote, viable, and nonviable regions. MBFs at rest (p?<?0.05) and stress (p?<?0.05) in viable regions were significantly higher than that in nonviable regions, while MFRs did not differ significantly (p?>?0.05). Compared to MFR in remote myocardium, MFRs in viable regions were similar (1.39?±?0.56 vs 1.70?±?0.45, p?>?0.05) but were significantly lower in nonviable regions (1.23?±?0.43, p?<?0.001). Moreover, the FDG and thus glucose extraction was higher in viable than in remote (1.40?±?0.14 vs 0.90?±?0.20, p?<?0.001) and in nonviable regions (1.13?±?0.21, p?<?0.001). The extraction of FDG in viable regions was independent of rest MBF but correlated inversely with MFRs (r?=?0.424, p?<?0.05). No correlation between the FDG extraction and MFR was observed in nonviable regions.

Conclusion

As in the animal model, decreasing MFRs in viable myocardium are associated with increasing glucose extraction that likely reflects a metabolic adaptation of remodeling hibernating myocytes.     

Long-term follow-up studies on Iodine-131 treatment of hyperthyroid graves’ disease based on the measurement of thyroid volume by ultrasonography

In the present series of studies, the long-term (four year) effect of 80 Gy of¹³¹I treatment was evaluated in patients with hyperthyroid Graves’ disease whose thyroid volumes have been accurately estimated with a high resolution ultrasound scanner. One year after¹³¹I treatment, 23.1 % (3 out of 13 patients) remained hyperthyroid, 69.2% (9 out of 13) became euthyroid, and 7.7% (1 out of 13) were in a hypothyroid state. Since three patients in a hyperthyroid state one year after treatment were subsequently treated with either antithyroid drugs or additional¹³¹I treatment, the remaining ten patients (9 euthyroid and 1 hypothyroid patients) have been followed up for three more years. Two patients developed a hypothyroid state three years after treatment and one patient four years after treatment. Overall, 60% (6 out of 10 patients) were in a euthyroid state and 40% (4 out of 10) in a hypothyroid state, four years after 80 Gy¹³¹I treatment. There was no significant difference between eu- and hypothyroid groups in the sex ratio, age, radiation dose, therapeutic dose, thyroid gland volume, 24-hr¹³¹I uptake, the effective half-life of¹³¹I in the thyroid or the duration of hyperthyroidism. In our preliminary studies, the incidence of late hypothyroidism in our¹³¹I treatment is similar to those previously reported. These suggest that uncertain factor(s), such as inhomogeneity of iodine distribution in the thyroid, unequal sensitivity of the thyroid cells to the radiation, and/or persistent destructive effects of the autoimmune process may influence the long-term effect of¹³¹I treatment of Graves’ disease.     

Kinetics of111In-labeled bleomycin in patients with brain tumors: Compartmental vs. non-compartmental models

The kinetics of an indium-111 labeled bleomycin complex (¹¹¹In-BLMC) after rapid intravenous injection in patients with brain tumors was quantified by using compartmental and non-compartmental models. The models were applied to data obtained from 10 glioma, one meningioma, and one adenocarcinoma brain metastasis patients. Blood and urine samples from all the patients and tumor samples from three patients were collected. The mean transit time of¹¹¹In-BLMC in the plasma pool was 14 ± 7 min without and 1.8 ± 0.6 h when accounting for recirculation, and 13 ± 4 h in the total body pool. The mean plasma clearance of¹¹¹In-BLMC was 0.3 ± 0.1 ml blood/min and the mean half-life in urine was 3.5 ± 0.6 h. The mean transfer coefficients for the open three-compartmental model were: excretion from plasma = 0.02 ± 0.01, from depot to plasma = (12 ± 9)*10^?4, from plasma to depot = 0.01 ± 0.01, from tumor to plasma = 0.39 ± 0.19 and from plasma to tumor = 1.11 ± 0.57, all in units minute^?1. The mean turnover time from the tumor was 4.5 ± 2.7 min and from the depot 20 ± 8 h. It is concluded that both compartmental and non-compartmental models are sufficient to describe the kinetics of indium-111 labeled bleomycin complex. The non-compartmental model is more practical and to some extent more efficient in describing thein vivo behaviors of¹¹¹In-BLMC than the compartmental model. The compartmental model used provides estimates of both extraction and excretion from the plasma and tumor.     

The influence of saliva flow stimulation on the absorbed radiation dose to the salivary glands during radioiodine therapy of thyroid cancer using 124I PET(/CT) imaging

Purpose

A serious side effect of high-activity radioiodine therapy in the treatment of differentiated thyroid cancer is radiogenic salivary gland damage. This damage may be diminished by lemon-juice-induced saliva flow immediately after ¹³¹I administration. The aim of this study was to assess the effect of chewing lemon slices on the absorbed (radiation) doses to the salivary glands.

Methods

Ten patients received (pretherapy) ¹²⁴I PET(/CT) dosimetry before their first radioiodine therapy. The patients underwent a series of six PET scans at 0.5, 1, 2, 4, 48 and ≥96 h and one PET/CT scan at 24 h after administration of 27 MBq ¹²⁴I. Blood samples were also collected at about 2, 4, 24, 48, and 96 h. Contrary to the standard radioiodine therapy protocol, the patients were not stimulated with lemon juice. Specifically, the patients chewed no lemon slices during the pretherapy procedure and neither ate food nor drank fluids until after completion of the last PET scan on the first day. Organ absorbed doses per administered ¹³¹I activity (ODpAs) as well as gland and blood uptake curves were determined and compared with published data from a control patient group, i.e. stimulated per the standard radioiodine therapy protocol. The calculations for both groups used the same methodology.

Results

A within-group comparison showed that the mean ODpA for the submandibular glands was not significantly different from that for the parotid glands. An intergroup comparison showed that the mean ODpA in the nonstimulation group averaged over both gland types was reduced by 28% compared to the mean ODpA in the stimulation group (p=0.01). Within each gland type, the mean ODpA reductions in the nonstimulation group were statistically significant for the parotid glands (p=0.03) but not for the submandibular glands (p=0.23). The observed ODpAs were higher in the stimulation group because of increased initial gland uptake rather than group differences in blood kinetics.

Conclusion

The ¹²⁴I PET(/CT) salivary gland dosimetry indicated that lemon juice stimulation shortly after ¹³¹I administration in radioiodine therapy increases the absorbed doses to the salivary glands.     

Aptitudes cardiorespiratoires et fonction musculaire périphérique chez des patients coronariens

Objective. – The aim of this study is to determine if the diminished aerobic capacity of coronary artery disease patients is accompanied by a impaired peripheral skeletal muscle function compared to healthy control subjects.Methods. – Thirteen coronary patients and 9 healthy control subjects (57 ± 7 vs 55 ± 8 years) have realised both a maximal laboratory exercise testing and an assessment of the peripheral skeletal muscle function on a isokinetic apparatus (Cybex Norm II). The cardiorespiratory and mechanical parameters (VO₂ uptake, VE, HR and Power output) were measured at ventilatory threshold and maximal effort during a cycloergometer testing. The peripheral skeletal muscle function of the quadriceps was assessed from the maximal voluntary isometric force (MVIF) and from static endurance time (SET) at an intensity of 50% of the MVIF.Results. – Coronary patients showed a diminished aerobic capacity at maximal effort (VO_2max: 23.56 ± 8.1 vs 42.43 ± 9.74 ml min^–1 kg^–1, p < 0.0001; VE_max: 67.07 ± 16.85 vs 90.15 ± 20.76 l min^–1, p < 0.01; HR_max: 110 ± 17 vs 153 ± 20 beats min^–1, p < 0.0001; P_max: 133 ± 40 vs 233 ± 39 W, p < 0,001) but also at ventilatory threshold (VO₂: 15.81 ± 5.7 vs 29.61 ± 7.8 ml min^–1 kg^–1, p < 0.001; HR: 92±11 vs 135±21 beats.min^–1, p < 0.0001, P: 88 ± 32 vs 153 ± 39 W, p < 0.001) except for VE (VE: 38.98 ± 9.91 vs 46.68 ± 7.03 l min^–1, NS). No difference was found between the MVIF (MVIF: 230 ± 46 vs 228 ± 21 N m^–1, NS) between coronary patients and control subjects whereas the SET is lower in coronary patients (65 ± 19 vs 88 ± 9 s, p < 0.003).Conclusion. – Coronary artery disease patients have a lower aerobic capacity accompanied by a impaired peripheral skeletal muscle function.     

Low levels of serum thyroglobulin after withdrawal of thyroid suppression therapy in the follow up of differentiated thyroid carcinoma

We evaluated the reliability of very low serum thyroglobulin (Tg) levels (< 3 ng/ml) obtained after withdrawal of thyroid suppression therapy in 224 patients without anti-Tg antibodies, who had undergone total thyroidectomy (125 patients) or thyroidectomy followed by 1 or more courses of¹³¹I therapy (99 patients), by performing whole body scans after a therapeutic course of¹³¹I given at the same time of Tg measurement. In 79 patients (35%) a positive scan, associated with a very low level of Tg, was noted. The 1311 uptake was limited to the thyroid bed in 60 patients, but metastases were demonstrated in 19 patients (8.5%). These results are mainly explained by the much improved performance of scintigraphy after administration of therapeutic doses of¹³¹I. In the majority of patients, especially those whose¹³¹I uptake was limited to the thyroid bed, further scans were negative. Therefore, in these cases, negative Tg values can generally be considered an early indication of satisfactory evolution. However, in 8.5% of all cases, very low Tg levels were associated with metastases. Thus the follow up of thyroid cancer should not rely only upon Tg determination, even after suppression therapy withdrawal.Presented in part as an oral communication at the European Nuclear Medicine Congress, Budapest, Hungary, 1987     

Quantitative evaluation of non-ischemic dilated cardiomyopathy by late iodine enhancement using rapid kV switching dual-energy computed tomography: A feasibility study

ObjectivesThe aim of this study was to evaluate the feasibility of myocardial iodine density and extracellular volume fraction (ECV) from delayed iodine density images using dual-energy computed tomography (DECT) for differentiation between non-ischemic dilated cardiomyopathy (NIDCM) patients and normal subjects.MethodsForty-six subjects were imaged, including 35 normal subjects and 11 patients with NIDCM. All subjects underwent myocardial delayed enhancement (MDE) imaging on rapid-kVp switching DECT. Global and segmental iodine density and ECV were calculated from MDE images. Histogram analysis was also performed. Receiver-operator characteristic (ROC) analysis was used to determine the cut-off value and diagnostic performances in differentiating NIDCM patients from normal subjects.ResultsGlobal iodine density and ECV were significantly higher in NIDCM compared with normal controls (iodine: 14.19 ± 3.90 vs. 10.69 ± 1.88 in 100 μg/cm³, p = 0.015; ECV: 31.35 ± 2.53% vs. 26.62 ± 2.69%, p < 0.001). In histogram analyses, kurtosis was higher in NIDCM than in controls (0.47 ± 0.46 vs. 1.26 ± 0.88, p < 0.001). On segmental analysis, ECV showed higher values in NIDCM than in controls for all segments. ECV could differentiate between normal myocardium and NIDCM with 91.0% sensitivity and 86.0% specificity at a cut-off of 28.82% (area under the curve of ROC, 0.906). Iodine density could differentiate between normal myocardium and NIDCM with 91% sensitivity and 60% specificity at a cut-off of 11.18 (area under the curve of ROC, 0.812).ConclusionsIodine density and ECV values from DECT may provide indices offering high diagnostic accuracy for discriminating between NIDCM and normal myocardium.