Local recurrence of breast cancer demonstrated on 99mTc-MIBI scintigraphy

We present a postmastectomy patient in whom a mass was palpated in the chest wall. It appeared to be difficult to determine whether the chest wall mass was local recurrence of breast cancer or granulation induced by mastectomy on computed tomography (CT). The mass was successfully demonstrated on 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) scintigraphy as an area of increased accumulation, and was considered to be a recurrent tumor. Surgical resection was performed, and the mass was histopathologically proven to be recurrence. 99mTc-MIBI scintigraphy may contribute to the detection of local recurrence or distant metastasis in addition to the diagnosis of primary breast cancer and axillary metastasis.     

Use of99mTc-MIBI scintigraphy in the evaluation of the response of osteosarcoma to chemotherapy

The use of gamma camera scintigraphy with technetium-99m hexakis-2-methcxyisobutylisonitrile (^99mTc-MIBI) for assessment of the response of high-grade osteosarcoma to preoperative chemotherapy was evaluated. Twelve patients with osteosarcoma of the extremities underwent planar examination with^99mTc-MIBI before and after preoperative chemotherapy according to the recommendations of the Scandinavian Sarcoma Group. After calculating a quotient for the tumour and the average activity of both extremities and correcting for background activity, the change in uptake between the two examinations was assessed. This was compared with histological examination of the ultimately resected specimen in 11 patients and progressive clinical disease in one. All the 11 tumours undergoing histological examination showed cellular necrosis of between 50% and 100% as well as a reduced uptake of^99mTc-MIBI, while the single progressive tumour showed an increased uptake. There was a correlation between the reduction of radiopharmaceutical uptake and the histological response in the entire series, while the variation was too large to allow conclusions in individual patients. This variation may have biological reasons or may be due to the planar imaging technique, which only allows semi quantitative evaluation. The technique reflects response to therapy but is not yet clinically applicable for the identification of poor responders, which would serve as a basis for alteration of the chemotherapy regimen. In order to evaluate whether such a role could be fulfilled, further studies using single-photon emission tomography with correction for attenuation and scattering of photons are necessary.     

Predictive value of (99m)Tc sestamibi scintigraphy in the evaluation of doxorubicin based chemotherapy response in patients with advanced breast cancer

Resistance to doxorubicin based chemotherapy is a major therapeutic problem limiting advanced breast cancer treatment. 99mTc hexakis-2-methoxyisobutylisonitrile ((99m)Tc-MIBI) has been reported to be extruded from tumour cells by the P-glycoprotein and multidrug resistance protein encoded by MDR1 and MRP1 genes, respectively. These proteins are involved in the cellular efflux of several chemotherapeutic agents including doxorubicin. The aim of this study was to investigate the clinical value of a standard (99m)Tc-MIBI scintimammography technique in the prediction of response to chemotherapy in advanced breast cancer patients. Fifty-six lesions from 33 female patients with locally advanced (n=27) or recurrent breast cancer (n=6) were included in the study. MIBI scintigraphy was performed 2-8 days prior to chemotherapy (FAC regimen). Images were acquired 10 min and 1 h post-injection of 740-1110 MBq of (99m)Tc-MIBI. Tumour-to-normal background tissue uptake ratios were calculated on each lesion in the early (T/B(e)) and delayed phase of the study (T/B(d)). Both T/B(e) and T/B(d) ratios were significantly higher (P<0.0001) in responders (n=43) than nonresponders (n=13). Diagnostic values of (99m)Tc-MIBI in the prediction of chemotherapy response were evaluated using the arbitrary cut-off values of 1.5 for T/B(e) and 1.4 forT/B(d). Sensitivity, specificity, positive and negative predictive values were 88.4%, 92.3%, 97.4%, 70.6%; and 90.7%, 100.0%, 100.0%, 76.6%, for T/B(e) and T/B(d), respectively. We conclude that (99m)Tc-MIBI scintigraphy may be a clinically valuable tool for guiding chemotherapy in advanced breast cancer patients.     

The effect of chemotherapy on the uptake of technetium-99m sestamibi in breast cancer

Technetium-99m sestamibi scintimammography has been used primarily in the diagnosis of breast cancer. It has also been suggested that this technique could be used to monitor response to chemotherapy and possibly to predict those patients in whom no response can be expected. An initial study was performed in nine patients with primary breast cancer. All patients underwent prone lateral and anterior^99mTc-sestamibi imaging at diagnosis and 4–7 months later, after they had received cytotoxic chemotherapy. The uptake of^99mTc-sestamibi in the breast was compared with that in normal surrounding breast tissue and this ratio was expressed as the target to background ratio. In all patients treated there was a reduction in uptake of^99mTc-sestamibi after treatment, such that whilst all the tumours could be seen before treatment, only three were visible following chemotherapy. There was a significant fall in the mean target to background ratio of the patients undergoing chemotherapy: the tumour to background ratio was 2.48 before chemotherapy and 1.40 after treatment (P<0.001, paired Student'st test). This fall in tumour activity was observed both in those patients in whom a clinical response was seen and in the two patients in whom the tumour enlarged despite chemotherapy. It appears that the reduced uptake of^99mTc-sestamibi seen after chemotherapy may be a non-specific change and therefore may not be predictive of the clinical response to treatment.     

Prognostic value of (99m)Tc-sestamibi washout in predicting response of locally advanced breast cancer to neoadjuvant chemotherapy.

This study evaluated the role of (99m)Tc-sestamibi washout in the prediction of pathologic tumor response to neoadjuvant chemotherapy in 30 patients with locally advanced breast cancer. METHODS: Two (99m)Tc-sestamibi studies were performed before and after chemotherapy for each patient. Early (10 min) and delayed (240 min) planar breast views were acquired after a 740-MBq (99m)Tc-sestamibi intravenous injection, and the washout rate (WOR) was computed. All patients underwent radical mastectomy with pathologic evaluation of the residual tumor size. RESULTS: The pretherapy (99m)Tc-sestamibi WOR ranged from 14% to 92% (mean +/- SD, 50% +/- 18%). At pathologic examination, 15 patients showed no tumor response to chemotherapy and 15 patients showed an objective response to chemotherapy. The pretherapy (99m)Tc-sestamibi study predicted chemoresistance (WOR > 45%) in 18 of 30 patients and no chemoresistance (WOR < or = 45%) in 12 of 30 patients. When the WOR cutoff was set at >45%, the prognostic performance of the test was indicated by a sensitivity of 100%; a specificity of 80%; positive and negative predictive values of 83% and 100%, respectively; and a likelihood ratio of 5. The repeatability of the test was good, with 80%-93% interreader agreement (kappa = 0.57-0.85). Posttherapy (99m)Tc-sestamibi studies confirmed the pretherapy study prediction in 29 of 30 patients. CONCLUSION: (99m)Tc-Sestamibi WOR is a reliable test for predicting tumor response to neoadjuvant chemotherapy. In fact, negative findings (WOR < or = 45%) rule out chemoresistance and positive findings (WOR > 45%) indicate a high risk of chemoresistance.     

Tc-99m tetrofosmin uptake in male breast cancer

Breast carcinoma occurs rarely in men. Its imaging by mammography is difficult because male breast tissue is normally small in volume and adequate compression is not possible, which is a prerequisite for performing mammography. The authors describe a 65-year-old man with a right breast mass in whom the result of fine-needle aspiration cytology was inconclusive. A mammogram was also noncontributory because adequate compression was not possible as the mass was tender. Tc-99m tetrofosmin scintimammography showed intense focal uptake in the right breast. Excision biopsy confirmed the diagnosis of breast carcinoma.     

99mTc-MIBI scintigraphy in metastatic renal cell carcinoma: clinical validation of the relationship between99mTc-MIBI uptake and P-alvcoprotein expression in tumour tissue

Technetium-99m hexakis-2-methoxyisobutyl-isonitrile (MIBI) and thallium-201 imaging was performed in a patient with metastatic renal cell carcinoma (RCC), which is a well-known tumour type demonstrating P1-glycoprotein (PGP) overexpression. Two scintigraphic patterns - TI(+)/MIBI(–) in primary tumour and TI(+)/MIBI(+) in metastatic tumour — were observed, suggesting high- and low-level PGP expression, respectively. Immunochemical study for PGP revealed strong staining of the primary tumour cells. This case clinically validates the previously suggested relationship between^99mTc-MIBI uptake and PGP expression.     

99mTc-MIBI in the evaluation of breast cancer biology

A major area of interest in nuclear medicine is the scintigraphic in vivo evaluation of complex cellular processes involved in tumour growth, progression and response to treatment with the aim of defining the biological properties that may orient clinicians towards different adjustments of therapy in individual patients. In the last decade, (99m)Tc-labelled lipophilic cations emerged as suitable tools to trace specific cellular processes and functions in a variety of malignant tumours, including breast cancer. Among these agents, (99m)Tc-methoxyisobutylisonitrile (MIBI) is the most widely evaluated tracer and may serve as a paradigm for this class of compounds. Many clinical studies have been performed to correlate (99m)Tc-MIBI uptake or clearance with histological, molecular and biochemical markers of various cellular processes, including apoptosis, proliferation, P-glycoprotein expression and neoangiogenesis. The final picture emerging from these studies is that the early tracer uptake reflects the mitochondrial status, which is affected by both apoptosis and proliferation, whereas the tracer clearance reflects the activity of drug transporters such as P-glycoprotein. On the basis of the imaging parameter chosen for the analysis of (99m)Tc-MIBI scan in breast cancer patients, the biological information provided may be related to different cellular processes that ultimately govern tumour response to treatment.     

Mammography and 99mTc-MIBI scintimammography in suspected breast cancer.

The aim of this work has been to evaluate whether a diagnostic protocol based on the joint use of mammography and 99mTc-methoxyisobutyl isonitrile (MIBI) scintimammography is capable of reducing the number of biopsies required in patients with suspected breast cancer. METHODS: We performed prone scintimammography in 90 patients with suspected breast cancer, involving 97 lesions. In all patients, the diagnosis was established by way of biopsy. On mammography, we evaluated the degree of suspicion of malignancy and the size of the lesion (smaller or larger than 1 cm in diameter). RESULTS: The results of only 41 of the biopsies indicated malignancy. On mammography, 20 lesions (of which 1 was breast cancer) were considered to be of low suspicion of malignancy, 31 (of which 4 were breast cancer) as indeterminate and 46 (of which 36 were breast cancer) as high. Fourteen lesions (2 low probability, 2 indeterminate and 10 high) were smaller than 1 cm, whereas 83 (18 low probability, 29 indeterminate and 36 high) were larger. The sensitivity, specificity, positive predictive value and negative predictive value of scintimammography were 85%, 79%, 74% and 88%, respectively. Scintimammography was positive in all cases of breast cancer that initially had a low or indeterminate suspicion of malignancy according to mammography, as well as in 30 cases of breast cancer that initially were highly suspicious. Six false-negative scintimammography studies were obtained in lesions with a high suspicion of malignancy. CONCLUSION: We propose a diagnostic protocol with a biopsy performed on lesions that have a high suspicion of malignancy as well as those with low or indeterminate suspicion that are smaller than 1 cm or with positive scintimammography results. This would have reduced the total number of biopsies performed by 34%. More importantly, there would have been a 65% reduction in number of biopsies performed in the low and indeterminate mammographic suspicion groups. All 41 cases of breast cancer would have been detected.     

~(99)Tc~m-MIBI显像在非霍奇金淋巴瘤化疗疗效评价中的价值

目的探讨99Tcm-MIBI显像在非霍奇金淋巴瘤疗效评价及提示预后方面的临床价值。方法对20例非霍奇金淋巴瘤病人于化疗前后分别行99Tcm-MIBI早期(10 min)与延迟(120 min)双时相显像,计算每例病人早期摄取率(EUR)、延迟期摄取率(DUR)及洗脱率(WR%)并进行比较。对99Tcm-MIBI显像结果进行疗效评价。平均随访时间34个月。结果 8例病人化疗后99Tcm-MIBI显像阴性,达完全缓解(CR)。12例病人化疗后99Tcm-MIBI显像阳性,其中4例达部分缓解(PR),2例处于稳定(SD)状态,6例进展(PD)。将病人分为化疗有效组(CR+PR)12例,疗效不佳组(SD+PD)8例。20例病人化疗后DUR明显低于化疗前(1.2±0.7∶2.9±1.2,P0.05)。化疗有效组与疗效不佳组相比,前者化疗前的DUR值高于后者(2.9±1.2∶1.5±0.9,P0.05),WR%低于后者(21.9±2.4∶42.7±5.6,P0.05),而前者化疗后的DUR值低于后者(1.0±0.2∶2.0±0.3,P0.05)。结论 99Tcm-MIBI作为一种功能性显像,有助于预测、评价非霍奇金淋巴瘤病人的疗效及预后。     

The role of Tc-99m sestamibi imaging in predicting clinical response to chemotherapy in lung cancer

Multidrug resistance (MDR) is a major problem in lung cancer. Tc-99m methoxyisobutyl isonitrile (MIBI) has been demonstrated to be a non-invasive marker to diagnose MDRI related P-glycoprotein (Pgp) and multidrug resistance-associated protein (MRP) expression in various solid tumors. The aim of this study was to evaluate the relationship between the degree of Tc-99m MIBI uptake and its retention on delayed images and the response to chemotherapy in lung cancer. Twenty-three patients (1 woman and 22 men, age range 40-67 years) with lung cancer (9 small cell and 14 non-small cell) were examined with Tc-99m MIBI imaging before chemotherapy. After i.v. administration of 740 MBq Tc-99m MIBI, planar and SPECT imaging at 30 minutes and 2 hours was performed. Tumor to normal lung uptake ratio (T/N) and percent retention were measured. Response to chemotherapy was evaluated according to follow-up CT and grouped as complete responders (CR), partial responders (PR) and non-responders (NR). Clinical follow-up and CT evaluation revealed that 12 patients had partial remission, 4 patients had complete remission and 7 patients had no-remission after chemotherapy. Statistically, there was no significant correlation between early (30 min), delayed (2 hr) T/N ratios and percent retention of Tc-99m MIBI with chemotherapeutic response of the lung cancer among the three groups (p > 0.05). Results of the current study imply that Tc-99m MIBI uptake and the retention index may not correlate with chemotherapy response in lung cancer, so that the accuracy of this method needs to be verified in a larger series with additional investigation at the molecular level.     

Comparison of uptake of99mTc-MIBI,99mTc-tetrofosmin and99mTc-012 into human breast cancer cell lines

Technetium-99m hexakis-2-methoxyisobutylisonitrile (MIBI),^99mTc-tetrofosmin and^99mTc-Q12 were all introduced for myocardial imaging but found additional applications as they are taken up by different tumours, enabling imaging of these lesions in patients. The aim of this study was to compare the uptake characteristics of these compounds in vitro in the human adenocarcinoma breast cell lines MCF-7 and ZR-75. It was shown that^99mTc-MIBI had the highest cellular uptake (15.9%±0.5% dose/mg protein after 60 min in MCF-7, and 14.2%±0.4% dose/mg protein in ZR-75), followed by^99mTc-tetrofosmin (6.8%±0.6% dose/mg protein in MCF-7, and 8.2%±0.2% dose/mg protein in ZR-75) and^99mTc-Q12 (3,2%±0. I% dose/mg protein in MCF-7, and 3.5%±0.3% dose/mg protein in ZR-75 cells). For all three compounds tenfold differences in specific activity did not influence total cell-associated radioactivity. Uptake of^99mTc-MIBI and^99mTc-tetrofosmin was obviously lower at 4° C than at 37° C, whereas^99mTc-Q12 uptake showed only slight temperature dependence. When uptake was compared in cells grown to different cell densities (1 mg/ml cellular protein versus 0.3 mg/ml), no differences in uptake were detected when uptake was corrected for the amount of cellular protein present in the dishes. Furthermore, for all compounds it was shown that cellular radioactivity decreased rapidly after washing. Apart from the differences in cellular uptake of the three compounds after 60 min, no differences in residual cellular radioactivity after washing were found between the different compounds when expressed as a percentage of their 60-min uptake, suggesting that the efflux process of the radiolabelled compounds was similar. The differences in cell-associated activity after 60 min were thus presumably caused by differences in uptake. It was concluded that of the Tc-labelled compounds tested,^99mTc-MIBI had the highest cellular retention in both human breast tumour cell lines. However, for imaging in vivo not only radioactivity in the target organ is important, but also the ratio of radioactivity in the target versus that in the background. Therefore, further studies in vivo need to be performed to investigate which compound is the optimal imaging agent     

99mTc-MIBI SPECT in small cell lung cancer patients before chemotherapy and after unresponsive chemotherapy

We evaluated the accumulation of 99mTc-MIBI in small cell lung cancer patients before chemotherapy and after unresponsive chemotherapy. The pre-chemotherapeutic group included 22 newly diagnosed patients. These patients underwent a 99mTc-MIBI SPECT study before starting chemotherapy. After chemotherapy, based on changes in tumor size, three different patterns of response (complete remission: CR, partial remission: PR and no change: NC) were defined. The post-chemotherapeutic group included 11 patients after chemotherapy who did not respond to chemotherapy. These patients underwent a 99mTc-MIBI SPECT study after completion of chemotherapy. SPECT images were acquired 15 min (early) and 2 hr (delayed) after injection of 99mTc-MIBI. With a region of interest technique, the early ratio, delayed ratio and retention index were calculated. Early and delayed ratios in pre-chemotherapeutic patients were significantly higher than those in post-chemotherapeutic patients. There were no significant differences between the pre-chemotherapeutic and post-chemotherapeutic patients in the retention index. In the pre-chemotherapeutic patients, early and delayed ratios for the CR and PR groups were significantly higher than those for the NC group. There were no significant differences in the retention index with respect to the tumor response. 99mTc-MIBI might be useful for evaluating the tumor chemosensitivity in patients with small cell lung cancer.     

Paclitaxel-Based chemotherapy for non-small cell lung cancer: predicting the response with 99mTc-tetrofosmin chest imaging.

The purpose of this study was to retrospectively predict the chemotherapeutic response to paclitaxel for non-small cell lung cancer (NSCLC) using 99mTc-tetrofosmin (TF) uptake and to detect the expression of 170-kDa multidrug resistance-mediated P-glycoprotein (MDR-Pgp). METHODS: Before chemotherapy with paclitaxel, 20 patients with stage IIIb or IV NSCLC were enrolled in this study to undergo early and delayed 99mTc-TF chest imaging for calculating tumor-to-normal lung ratios (T/NL) and retention indices (RI) for assessment of the MDR-Pgp in NSCLC. RESULTS: The early and delayed mean T/NLs were 1.59 +/- 0.25 and 1.50 +/- 0.25, respectively, for 10 patients with a good response and 1.09 +/- 0.09 and 1.03 +/- 0.05, respectively, for 10 patients with a poor response. The differences were shown to be significant (P < 0.001) by independent Student t tests. However, no significant differences (P = 0.801) between good-response patients (-5.70% +/- 3.67%) and poor-response patients (-5.23% +/- 4.51%) were found in RI. In addition, other prognostic factors (age, sex, tumor size, stage, and cell type) were not significantly different between good-response patients and poor-response patients. CONCLUSION: 99mTc-TF chest images are potential tools for understanding MDR-Pgp expression in NSCLC and for predicting the chemotherapeutic response to paclitaxel.     

99Tcm-MIBI显像对乳腺癌腋窝转移淋巴结的诊断

目的 评价＾９９Ｔｃ＾ｍ－甲氧基异丁基异腈（ＭＩＢＩ）显像要诊断乳腺癌腋窝转移淋巴结中的价值,方法 １８例病理检查证实的乳腺癌病人,术前均行＾９９Ｔｃｍ－ＭＩＢＩ显像,１４例乳腺未触及肿块者作为对照组,静脉注射＾９９Ｔｃ＾ｍ－ＭＩＢＩ１１０ＭＢｑ后５,３０和６０ｍｉｎ进行早期及延迟显像,分别于左侧位,右侧位和前后位进行观察,患者均在显像扣１周内进行手术治疗,腋窝淋巴结清扫后行病理检查。结果 １８例     

Tc-99m DMSA renal uptake: influence of biochemical and physiologic factors

Thirty-eight female Sprague-Dawley rats were studied to determine the effects of (a) tubular blockade and (b) commonly encountered changes in hydration and acid-base balance, on the urinary excretion and renal localization of Tc-99m dimercaptosuccinic acid (DMSA). Ten additional rats were studied to quantitate the in vivo protein binding of Tc-99m DMSA, and a final group of 12 animals was used to quantitate DMSA distribution in animals with diminished functional renal mass. Both osmotic diuresis and dehydration by water deprivation for 24 hr resulted in a plasma clearance of DMSA slower than in control animals. Acid-base imbalances significantly affected the renal accumulation of DMSA, and acidosis was associated with markedly increased background due to increased liver accumulation. The protein-bound portion of Tc-99m DMSA in the plasma was high, reaching 89% within the first 5 min, and rising very slightly (n.s.) ith time. The unbound portion of DMSA had a plasma clearance slightly higher than the GFR. Ablation of large amounts of renal tissue, resulting in significant decreases in GFR. Ablation of large amounts of renal tissue, resulting in significant decreases in GFR, did not significantly affect the renal localization of DMSA in the intact portions of the kidneys. These data demonstrate that commonly encountered changes in acid-base balance and hydration will significantly alter the biologic distribution of Tc-99m DMSA. These factors should be controlled when carrying out clinical studies.