201Tl Retention Research Articles

Decorporation potential of lansoprazole against radiothallium (201Tl) in internally contaminated BALB/c mice and New Zealand White rabbits.

This study examined the decorporation potential of lansoprazole (LNP) as radioactivity decorporation agent for radiothallium (201Tl) in internally contaminated BALB/c mice and New Zealand White rabbits using radiometry and gamma scintigraphy. Animals were divided into three groups, that is, control, pretreatment-1 (1X LNP), and pretreatment-2 (2X LNP). Mice received LNP intraperitoneally, while in rabbits LNP was given through oral route 0.5 and 1.5 h before radiothallium administration, respectively. Mice and rabbits used in the experiment were administered 1.48 and 11.1 MBq radiothallium (201TlCl) through intravenous and oral route, respectively. Once started as prophylactic, LNP was continued as therapeutic twice a day till the end of study period. Radiometry and gamma scintigraphy were used to monitor radiothallium retention and uptake patterns in animals. Gamma scintigraphic images of rabbits were taken at different time intervals up to 72 h and were analyzed for comparative uptake pattern of 201TlCl in all the groups. LNP treatment significantly increased the 201Tl elimination over untreated control and considerably reduced the retention of 201Tl in various tissues and organs. Decrease in radiothallium uptake up to 40% was observed in LNP-treated mice as compared to untreated control. While in rabbits, whole-body radioactivity burden at 72 h was found to be 31.24%, 26%, and 18.54% in untreated control, 9 and 18 mg/kg LNP-treated groups, respectively. LNP exhibited dose-dependent decorporation potential to effectively enhance the elimination of 201Tl in mice and rabbits experimentally contaminated with 201TlCl.

Uptake Behavior of Thallium-201 in Hindlimb Muscles of Rats

[Purpose] We aimed to examine the uptake and retention behavior of the radioisotope thallium-201(201Tl) in 5 hindlimb muscles, the soleus (Sol), plantaris (Pla), gastrocnemius (Gast), extensor digitorum longus (EDL), and tibialis anterior (TA). [Subjects] Male Wistar rats. [Methods] Three experiments were perfomed: 201Tl uptake and retention as a function of time after intravenous injection; uptake and retention under general anesthesia and in the conscious state; Analysis in hindlimb suspension model rats. [Results] There were significant differences between the uptake rates of Sol and other muscles. The uptake rates of the conscious group muscles were significantly higher than those of the unconscious group; the ratio of Sol/EDL uptake was approximately 2.5 for the conscious animals, although that for unconscious animals was 1.3. In hindlimb-suspended rats, no significant differences between Sol and EDL uptake rates were seem throughout the course of the experiment. [Conclusion] In summary, rat skeletal muscles are very sensitive to uptake and retention of 201Tl and are markedly dependent on time from injection, state of consciousness and on the muscular trophicity. The results of the present study suggest that 201Tl may contribute to physiological evaluation of muscle in rehabilitation science.

Comparison of thallium-201 uptake and retention indices for evaluation of brain lesions with SPECT

Thallium-201 chloride single photon emission computed tomography (201TlCl SPECT) has been applied extensively for studies of human tumors. To assess which indices for 201TlCl SPECT are most useful for diagnosing brain lesions, a total of 82 patients (98 images) with intracranial abnormalities were investigated. Seventy-six cases with abnormal 201Tl uptake were evaluated in terms of six different 201Tl uptake and retention indices: (1) average early 201Tl uptake=Av.Le/Av.Be; (2) maximum early 201Tl uptake=Mx.Le/Av.Be; (3)201 Tl retention A=Av.Ld/Av.Le; (4) 201Tl retention B=Mx.Ld/Mx.Le; (5) 201Tl retention C=(Av.Ld/Av.Bd)/(Av.Le/Av.Be); (6) 201Tl retention D=(Mx.Ld/Av.Bd)/(Mx.Le/Av.Be), where Av.Le and Mx.Le are average and maximum early counts for lesions, Av.Be and Av.Bd are average early and delayed counts for contralateral normal brains, and Av.Ld and Mx.Ld are average and maximum delayed counts for lesions. Comparison of patients with benign and malignant lesions did not demonstrate significant differences with any of the indices. However, low (I–II) and high (III–IV) grade astrocytomas varied in their average and maximum early 201Tl uptake indices (bothP =0.0026). For patients with and without meningiomas, P values for indices of maximum early201 Tl uptake and 201Tl retention A and B were 0.0338, 0.0005, 0.0002, respectively. While comparison of patients with metastatic brain tumors and gliomas again showed no significant differences between the groups, the presence or absence of calcification was associated with significant variation in all the indices. With 201TlCl-SPECT imaging, the average and maximum early 201Tl uptake indices are appropriate for the assessment of tumor viability or malignancy, while 201Tl retention indices (A,B) are useful for tumor differentiation, especially with meningiomas. Choice of suitable indices should enhance the utility of 201TlCl-SPECT imaging in pre- and postoperative evaluation of intracranial lesions.

Scintigraphic prediction of response to chemotherapy in patients with breast cancer: Technetium 99m-tetrofosmin and thallium-201 dual single photon emission computed tomography

We have investigated the usefulness of dual-isotope single photon emission computed tomography (SPECT) for predicting the response to chemotherapy in patients with breast cancer. Twenty-five patients with breast cancer were analyzed by SPECT using both 99m-technetium-tetrofosmin (99mTc-TF) and 201-thallium-chloride (201Tl). The relationship between response to chemotherapy and retention of each tracer was analyzed. 99mTc-TF retention was significantly higher in responders (42.0+/-37.9) than in non-responders (-11.3+/-34.6) (p=0.003). Ten of 13 patients (76.9%) with high 99mTc-TF retention (>15%) showed good response to chemotherapy, whereas 11 of 12 patients (91.7%) with low 99mTc-TF retention (<15%) did not respond to the therapy. The overall predictability to the response to chemotherapy was 84.0%. 201Tl retention (responders, 47.5+/-60.2% vs. non-responders, 55.8+/-45.0%; p=0.443) was not useful in therapeutic prediction, but was required to identify the lesion on the SPECT image. This is the first report to find that dual-isotope SPECT using 99mTc-TF and 201Tl is useful in predicting the response to chemotherapy in patients with breast cancer. Low 99mTc-TF retention is a strong predictor of therapeutic resistance, and high 99mTc-TF retention suggests a favorable response to chemotherapy.

Relationship between cancer cell proliferation and thallium-201 uptake in lung cancer.

Although thallium-201 (201Tl) uptake is related to perfusion in many normal tissues, the biologic rationale for 201Tl uptake in tumors is uncertain. To determine if tumor uptake is related to cell proliferation, we correlated the relative retention of 201Tl in lung tumors with expression of Ki-67, an indicator of cell proliferation. Sixty patients with lung tumors, included small cell carcinoma (n = 8) and non-small cell carcinoma (n = 52), underwent 201Tl single photon emission computed tomography (SPECT) imaging. The 201Tl lesion uptake was determined on early and delayed images and the radiotracer retention index (RI) was calculated. Tumor specimens were obtained at surgery or bronchoscopy. The cell proliferation ratio was estimated with MIB-1, a monoclonal antibody that recognized the nuclear antigen Ki-67. The average 201Tl index was 2.13+/-0.61 (early) and 2.46+/-0.83 (delayed). The average RI was 17.44+/-35.01. Overall, the 201Tl index (delayed) and the cancer cell proliferation were correlated (r = 0.70, p < 0.0001). Of interest, there was a significant correlation (r = 0.872, p < 0.0005) between the 201Tl index on delayed images and the cell proliferation ratio in patients with small cell but not non-small cell lung carcinoma. The 201Tl index (delayed) was significantly higher (p < 0.0001) in patients with small cell lung carcinoma than in patients with non-small cell lung carcinoma. 201Tl imaging appears to be useful for evaluating patients with small cell lung carcinoma but not non-small lung carcinoma, and is correlated with the monoclonal antibody MIB-1, a marker of cell proliferation.

Scintigraphic prediction of resistance to radiation and chemotherapy in patients with lung carcinoma

BACKGROUND Various prognostic markers for lung carcinoma have been proposed, but to the authors' knowledge none is noninvasive and convenient for clinical use. The current study examined the utility of several radiotracers for the prediction of multidrug resistance (MDR) and radioresistance in patients with lung carcinoma. METHODS Thirty patients with untreated lung carcinoma underwent a dual isotope single photon emission computed tomography (SPECT) scan at 10 minutes and 120 minutes after the injection of technetium-99m (99mTc)-tetrofosmin (99mTc-TF) (370 megabecquerels [MBq]) and thallium-201 (201TlCl) (111 MBq). Retention of each tracer was evaluated semiquantitatively. Using radiation and chemotherapy (cisplatin plus etoposide), the patients either were treated sequentially (n = 12) or concurrently (n = 18). The relation between therapeutic response and retention of each tracer was analyzed. The detectability of radioresistance was examined. RESULTS In patients treated with sequential therapy, the response to radiation was predicted by 99mTc-TF retention, whereas 201Tl retention was found not to be predictive. Regardless of whether the sequential or concurrent protocol was applied, 14 of 18 tumors with high 99mTc-TF retention (≥15%) exhibited a favorable response to chemoradiotherapy whereas all 12 tumors with low 99mTc-TF retention (≤15%) did not respond to the therapy. In contrast, 201Tl retention was not found to be a predictive factor. CONCLUSIONS The employed SPECT method is a useful tool for the in vivo prediction of radioresistance, P-glycoprotein (P-gp), and non-P-gp MDR in lung carcinoma. Low 99mTc-TF retention serves as a strong predictor of therapeutic resistance. High 99mTc-TF retention implies a favorable response. 201Tl did not appear to be a predictive factor but is required for localization of the lesion on SPECT imaging. Cancer 1999;86:1470–9. © 1999 American Cancer Society.

201Tl SPET in the differential diagnosis of brain tumours.

The aims of this study were to assess the utility of 201Tl single photon emission tomography (SPET) in the differential diagnosis of brain tumours and to elucidate the relationship between 201Tl tumour uptake and degree of contrast-enhancement on magnetic resonance imaging (MRI). Early (15 min) and delayed (3 h) 201Tl SPET imaging and T1-weighted MRI were performed before and after Gd-DTPA enhancement in 101 (41 malignant and 60 benign) untreated brain tumours. The 201Tl uptake ratio (tumour-to-normal brain count ratio) for both the early and delayed SPET studies and the retention index (the ratio of delayed to early 201Tl uptake) were calculated. Malignant tumours were separated from benign tumours with 87% accuracy based on the assumption that tumours with a 201Tl retention index < 0.7 or no abnormal uptake are benign. Meningiomas and pituitary adenomas were differentiated from other benign tumours by their characteristic pattern on SPET. The degree of contrast-enhancement of the tumour on MRI was concordant with the early 201Tl uptake ratio for most histological types. However, schwannomas and cavernous haemangiomas showed a low 201Tl uptake ratio in spite of a high degree of contrast-enhancement on MRI. In conclusion, 201Tl SPET provides additional information that helps in the differential diagnosis of brain tumours.

Super-normal 201Tl retention in hibernating myocardium: an ex-vivo study using the failing human heart.

Although the relationship between delayed 201Tl distribution and blood flow in acutely ischemic and infarcted myocardium has been widely explored in the experimental setting, its behaviour in chronically hypoperfused dysfunctioning human myocardium has not yet been evaluated. In tissue samples of excised failing hearts taken from ischemic (IHD) patients and idiopathic dilated cardiomyopathy (IDC) controls, we evaluated the relationship between delayed 201Tl retention (4 h redistribution), blood flow (assessed by means of 99mTc-labelled human albumin microspheres injected during transplantation) and biochemically-assessed fibrosis. 201Tl activity was expressed as the percent of the activity in the region with highest flow and the least fibrosis. Fibrosis and 201Tl activity were inversely related (r = -0.62, P = 0.0001). In IDC controls, low flows corresponded to uniformly preserved 201Tl retention. In IHD, 46 segments with flows < or = 0.60 ml.min-1.g-1 and 20 segments with flows > 0.60 ml.min-1.g1 showed matching delayed 201Tl retention and flow values; in the remaining 27, there was a disproportionately high tracer accumulation in comparison with flow (flow/201Tl mismatch). Despite significantly less fibrosis and lower flows, the mismatch segments showed significantly greater. 201Tl activity than the segments with concordantly high tracer retention and flow values. Conversely, at equivalent flow rates, the mismatch regions had less fibrosis than the areas with concordantly depressed 201Tl activity and perfusion. This super-normal 201Tl retention in hibernating myocardium may indicate a mechanism of cell adaptation to chronic hypoperfusion.

Difference in 201Tl accumulation on single photon emission computed tomography in benign and malignant thoracic lesions

The difference in 201Tl-chloride (201Tl) accumulation on single photon emission computed tomography (SPECT) between 58 benign (58 cases) and 48 malignant (46 cases) thoracic lesions, each of more than 20 mm in diameter was investigated. In the 34 benign and 48 malignant lesions depicted in both early (15 min) and delayed (3 h) images there was no significant difference in the mean early and delayed uptake ratios of lesion to normal contralateral lung between benign and malignant. However, the retention index in the lesion derived from (delayed ratio--early ratio)/(early ratio) x 100% showed a significant difference (benign -4.30 +/- 13.6% versus malignant 23.3 +/- 18.9%, P < 0.01), indicating the poor 201Tl retention in the benign lesions. Using the criteria of nondepiction in the delayed image or a negative retention index, 81.1% accuracy and 95.2% predictive value for diagnosis of benign lesions were obtained. Thus, 201Tl SPECT appears to have potential usefulness in the diagnosis of benign thoracic lesions.

Technetium-99m hexakis 2-methoxy-2-isobutyl isonitrile and thallium-201 extraction, washout, and retention at varying coronary flow rates in rabbit heart.

Technetium-99m hexakis 2-methoxy-2-isobutyl isonitrile (Tc-MIBI) and thallium-201 extraction, washout, and retention were investigated and compared in 20 isolated, isovolumic, retrograde blood-perfused rabbit hearts at flow rates ranging from 0.5 to 3.5 ml/g wet wt min-1 in the absence of tracer recirculation. Mean Tc-MIBI peak instantaneous extraction was lower (0.55 +/- 0.10, p less than 0.001) and more affected by flow rate (p less than 0.05) than 201Tl peak instantaneous extraction (0.83 +/- 0.06). In contrast, the rate of 201Tl washout was significantly faster (p less than 0.05) and initially more dependent on perfusion rate (p less than 0.05) than Tc-MIBI washout. Reflecting its higher peak instantaneous extraction, 201Tl retention was 55-79% higher immediately after isotope injection (p less than 0.001) than Tc-MIBI retention, and relative changes in maximal 201Tl net uptake correlated better (p less than 0.05) with relative flow changes than maximal Tc-MIBI net uptake. However, due to its faster washout rate, the superiority of thallium over Tc-MIBI as a perfusion indicator was lost within 10 minutes of tracer injection under the present single-pass experimental conditions. These data were interpreted to indicate that 1) Tc-MIBI is not as well extracted and has a slower washout rate than 201Tl; 2) varying the coronary flow rate has significant but divergent effects on the extraction, washout, and retention of Tc-MIBI and 201Tl; and 3) the present results support continued evaluation of Tc-MIBI as a possible perfusion indicator.