Full automation of total metabolic tumor volume from FDG-PET/CT in DLBCL for baseline risk assessments.

BACKGROUND: Current radiological assessments of 18fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging data in diffuse large B-cell lymphoma (DLBCL) can be time consuming, do not yield real-time information regarding disease burden and organ involvement, and hinder the use of FDG-PET to potentially limit the reliance on invasive procedures (e.g. bone marrow biopsy) for risk assessment. METHODS: Our aim is to enable real-time assessment of imaging-based risk factors at a large scale and we propose a fully automatic artificial intelligence (AI)-based tool to rapidly extract FDG-PET imaging metrics in DLBCL. On availability of a scan, in combination with clinical data, our approach generates clinically informative risk scores with minimal resource requirements. Overall, 1268 patients with previously untreated DLBCL from the phase III GOYA trial (NCT01287741) were included in the analysis (training: n = 846; hold-out: n = 422). RESULTS: Our AI-based model comprising imaging and clinical variables yielded a tangible prognostic improvement compared to clinical models without imaging metrics. We observed a risk increase for progression-free survival (PFS) with hazard ratios [HR] of 1.87 (95% CI: 1.31-2.67) vs 1.38 (95% CI: 0.98-1.96) (C-index: 0.59 vs 0.55), and a risk increase for overall survival (OS) (HR: 2.16 (95% CI: 1.37-3.40) vs 1.40 (95% CI: 0.90-2.17); C-index: 0.59 vs 0.55). The combined model defined a high-risk population with 35% and 42% increased odds of a 4-year PFS and OS event, respectively, versus the International Prognostic Index components alone. The method also identified a subpopulation with a 2-year Central Nervous System (CNS)-relapse probability of 17.1%. CONCLUSION: Our tool enables an enhanced risk stratification compared with IPI, and the results indicate that imaging can be used to improve the prediction of central nervous system relapse in DLBCL. These findings support integration of clinically informative AI-generated imaging metrics into clinical workflows to improve identification of high-risk DLBCL patients. TRIAL REGISTRATION: Registered clinicaltrials.gov number: NCT01287741.

Optimal timing and criteria of interim PET in DLBCL: a comparative study of 1692 patients.

Interim 18F-fluorodeoxyglucose positron emission tomography (Interim-18F-FDG-PET, hereafter I-PET) has the potential to guide treatment of patients with diffuse large B-cell lymphoma (DLBCL) if the prognostic value is known. The aim of this study was to determine the optimal timing and response criteria for evaluating prognosis with I-PET in DLBCL. Individual patient data from 1692 patients with de novo DLBCL were combined and scans were harmonized. I-PET was performed at various time points during treatment with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. Scans were interpreted using the Deauville score (DS) and change in maximum standardized uptake value (ΔSUVmax). Multilevel Cox proportional hazards models corrected for International Prognostic Index (IPI) score were used to study the effects of timing and response criteria on 2-year progression-free survival (PFS). I-PET after 2 cycles (I-PET2) and I-PET4 significantly discriminated good responders from poor responders, with the highest hazard ratios (HRs) for I-PET4. Multivariable HRs for a PET-positive result at I-PET2 and I-PET4 were 1.71 and 2.95 using DS4-5, 4.91 and 6.20 using DS5, and 2.93 and 4.65 using ΔSUVmax, respectively. ΔSUVmax identified a larger proportion of poor responders than DS5 did. For all criteria, the negative predictive value was >80%, and positive predictive values ranged from 30% to 70% at I-PET2 and I-PET4. Unlike I-PET1, I-PET3 discriminated good responders from poor responders using DS4-5 and DS5 thresholds (HRs, 2.94 and 4.67, respectively). I-PET2 and I-PET4 predict good response equally during R-CHOP therapy in DLBCL. Optimal timing and response criteria depend on the clinical context. Good response at I-PET2 is suggested for de-escalation trials, and poor response using ΔSUVmax at I-PET4 is suggested for randomized trials that are evaluating new therapies.

Cerebral [18 F]T807/AV1451 retention pattern in clinically probable CTE resembles pathognomonic distribution of CTE tauopathy.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disorder most commonly associated with repetitive traumatic brain injury (TBI) and characterized by the presence of neurofibrillary tangles of tau protein, known as a tauopathy. Currently, the diagnosis of CTE can only be definitively established postmortem. However, a new positron emission tomography (PET) ligand, [18F]T807/AV1451, may provide the antemortem detection of tau aggregates, and thus various tauopathies, including CTE. Our goal was to examine [18F]T807/AV1451 retention in athletes with neuropsychiatric symptoms associated with a history of multiple concussions. Here we report a 39-year-old retired National Football League player who suffered 22 concussions and manifested progressive neuropsychiatric symptoms. Emotional lability and irritability were the chief complaints. Serial neuropsychological exams revealed a decline in executive functioning, processing speed and fine motor skills. Naming was below average but other cognitive functions were preserved. Structural analysis of longitudinally acquired magenetic resonance imaging scans revealed cortical thinning in the left frontal and lateral temporal areas, as well as volume loss in the basal ganglia. PET with [18F]florbetapir was negative for amyloidosis. The [18F]T807/AV1451 PET showed multifocal areas of retention at the cortical gray matter-white matter junction, a distribution considered pathognomonic for CTE. [18F]T807/AV1451 standard uptake value (SUV) analysis showed increased uptake (SUVr⩾1.1) in bilateral cingulate, occipital, and orbitofrontal cortices, and several temporal areas. Although definitive identification of the neuropathological underpinnings basis for [18F]T807/AV1451 retention requires postmortem correlation, our data suggest that [18F]T807/AV1451 tauopathy imaging may be a promising tool to detect and diagnose CTE-related tauopathy in living subjects.

Tauopathy PET and amyloid PET in the diagnosis of chronic traumatic encephalopathies: studies of a retired NFL player and of a man with FTD and a severe head injury.

Single, severe traumatic brain injury (TBI) which elevates CNS amyloid, increases the risk of Alzheimer's disease (AD); while repetitive concussive and subconcussive events as observed in athletes and military personnel, may increase the risk of chronic traumatic encephalopathy (CTE). We describe two clinical cases, one with a history of multiple concussions during a career in the National Football League (NFL) and the second with frontotemporal dementia and a single, severe TBI. Both patients presented with cognitive decline and underwent [(18)F]-Florbetapir positron emission tomography (PET) imaging for amyloid plaques; the retired NFL player also underwent [(18)F]-T807 PET imaging, a new ligand binding to tau, the main constituent of neurofibrillary tangles (NFT). Case 1, the former NFL player, was 71 years old when he presented with memory impairment and a clinical profile highly similar to AD. [(18)F]-Florbetapir PET imaging was negative, essentially excluding AD as a diagnosis. CTE was suspected clinically, and [(18)F]-T807 PET imaging revealed striatal and nigral [(18)F]-T807 retention consistent with the presence of tauopathy. Case 2 was a 56-year-old man with personality changes and cognitive decline who had sustained a fall complicated by a subdural hematoma. At 1 year post injury, [(18)F]-Florbetapir PET imaging was negative for an AD pattern of amyloid accumulation in this subject. Focal [(18)F]-Florbetapir retention was noted at the site of impact. In case 1, amyloid imaging provided improved diagnostic accuracy where standard clinical and laboratory criteria were inadequate. In that same case, tau imaging with [(18)F]-T807 revealed a subcortical tauopathy that we interpret as a novel form of CTE with a distribution of tauopathy that mimics, to some extent, that of progressive supranuclear palsy (PSP), despite a clinical presentation of amnesia without any movement disorder complaints or signs. A key distinguishing feature is that our patient presented with hippocampal involvement, which is more frequently seen in CTE than in PSP. In case 2, focal [(18)F]-Florbetapir retention at the site of injury in an otherwise negative scan suggests focal amyloid aggregation. In each of these complex cases, a combination of [(18)F]-fluorodeoxyglucose, [(18)F]-Florbetapir and/or [(18)F]-T807 PET molecular imaging improved the accuracy of diagnosis and prevented inappropriate interventions.

The significance and management of incidental [18F]fluorodeoxyglucose-positron-emission tomography uptake in the thyroid gland in patients with cancer.

BACKGROUND AND PURPOSE: Incidental positron-emission tomography (PET) uptake in the thyroid bed represents a diagnostic dilemma. Currently, there is no consensus regarding the significance of this finding or the most appropriate approach to management. The purpose of this study was to determine the significance of incidental fluorodeoxyglucose (FDG) uptake in the thyroid gland on [(18)F]FDG-positron-emission tomography (FDG-PET/CT) in patients being initially staged for lymphomas and/or cancers other than of thyroid origin. MATERIALS AND METHODS: A retrospective review was conducted on patients who were incidentally found to have focal FDG uptake in the thyroid bed on initial staging for cancer. Patient records were assessed for age, sex, clinical presentation, standard uptake values (SUV(max)), on FDG-PET/CT, and CT findings in those patients undergoing FDG-PET/CT, fine-needle aspiration (FNA) cytology, and surgical pathologic examination. RESULTS: Thirty patients were identified with incidental FDG-PET uptake in the thyroid bed from 630 studies performed for evaluation of cancer between March 2004 and June 2006. Complete records were available for 18 patients (6 men, 12 women). Five (27.8%) of 18 patients with incidental focal FDG-PET/CT uptake in the thyroid gland demonstrated papillary thyroid carcinoma on final pathologic findings. The mean and SD of SUV(max) was 3.0 +/- 1.8 (range, 1.1-7.4) overall, 2.9 +/- 1.6 (range, 1.1-6.8) in the patients without malignant growth, and 3.4 +/- 2.6 (range, 1.1-7.4) in the 5 patients with papillary thyroid carcinoma. No statistical difference in SUV(max) was noted between patients with papillary thyroid carcinoma and patients with benign pathologic findings (P = .63). CONCLUSIONS: Incidental FDG-PET uptake in the thyroid gland in patients with cancer of nonthyroidal origin is associated with a 27.8% risk for well-differentiated thyroid carcinoma; however, there seems to be no correlation between intensity of FDG uptake and the risk for a malignant process.

High uptake in schneiderian papillomas of the maxillary sinus on positron-emission tomography using fluorodeoxyglucose.

Schneiderian papillomas are benign tumors of the nasal cavity and paranasal sinuses often asymptomatic in their early stages. We report a case of a maxillary sinus oncocytic schneiderian papilloma first detected by positron-emission tomography by using fluorodeoxyglucose (FDG). Schneiderian papillomas demonstrate increased FDG uptake, similar to that of other oncocytic tumors, making it important for otolaryngologists and radiologists to realize that high uptake of FDG does not necessarily indicate a malignant lesion.

Imaging Multidrug Resistance in Hematological Malignancies.

In hematological malignancies, multidrag resistance (MDR) has been associated with the drag efflux pumps: one is the classical Mr 170,000 P-glycoprotein (Pgp) and the other Mr 190,000 multidrag resistance-associated protein (MRP). In addition, the overexpression of a recently identified protein, lung resistance protein (LRP), is also associated with reduced intracellular drag accumulation and retention. Currently available detection methods may provide variable results among laboratories, as there is no single set of standards for detection techniques at the mRNA or protein level. Moreover, these methods may not be informative about the in vivo function of Pgp, MRP or LRP. Single-photon emission tomography (SPECT) and positron emission tomography (PET) have been evaluated for the non-invasive determination of Pgp- and MRP- mediated transport systems. Tc-99m-hexaxis-2-methoxyisobutyl isonitrile (Tc-99m-Sestamibi), an agent used in myocardial perfusion and tumor imaging, is a substrate for Pgp and MRP, and has been used for tumor imaging, and to visualize Pgp expression. Tc-99m-Tetrofosmin and several Tc-99m-Q complexes, are also recognized as substrates by Pgp pump mechanism. Moreover, radiopharmaceuticals including carbon-11-labeled colchicine, verapamil and daunorabicin have been used for the assessment of Pgp-mediated transport functions in vivo using PET technology. The results suggest that the potential exists for nuclear medicine imaging using either Tc-99m-labeled compounds and SPECT or carbon-11-labeled compounds and PET to detect MDR in tumors prior to or after exposure to chemotherapeutic agents.

Fluorine-18 fluorodeoxyglucose positron emission tomography in the staging and follow-up of lymphoma: is it time to shift gears?

Positron emission tomography (PET) imaging has become a very useful technique for staging and monitoring therapy response in lymphoma, providing unique information about the biological behavior of disease. Increased fluorine-18 fluorodeoxyglucose (FDG) uptake in lymphoma is based on elevated glycolysis and longer residence time of FDG in malignant cells compared with most normal tissues. The metabolic information provided by this technique suggests that FDG-PET may be more sensitive than the anatomical imaging modalities. Computed tomography (CT) is the principal imaging modality for the staging and restaging of lymphoma. Nonetheless, this technique has significant shortcomings, particularly in the post-therapy setting. Gallium-67 scintigraphy has played an important role in monitoring response to therapy and follow-up of patients; however, the sensitivity of 67Ga depends on the subtype of lymphoma and the size and location of disease. Published results strongly indicate that FDG-PET is superior to 67Ga imaging and may be equal or superior to CT for the detection of nodal as well as extranodal involvement in lymphoma.

Radiopharmaceuticals for the visualization of infectious and inflammatory lesions.

Many radiopharmaceuticals have been introduced for the scintigraphic demonstration of infectious and inflammatory lesions and some of them are currently in clinical use. They can be classified into two major categories according to their specificity. Specific radiopharmaceuticals include in vitro labeled leukocytes, radio-labelled monoclonal antibodies, and receptor specific small proteins and peptides. Nonspecific radiopharmaceuticals include radiolabelled nanocolloids, liposomes, macromolecules such as human immunoglobulin, dextran and human serum albumin, various small molecules and ions. In this review article radiopharmaceuticals in their respective groups are discussed as to the efficacy, and other parameters such as the physical characteristics of the radionuclides used, radiochemistry involved, availability, cost and biodistribution, emphasizing recent developments.

Nuclear medicine imaging of lung cancer.

Although nuclear medicine imaging is still widely under-appreciated and underused by the medical and radiologic communities, FDG PET imaging and Tc 99m depreotide SPECT imaging are safe, cost-effective methods with advantages over CT and other imaging methods in the diagnosis and management of patients suspected or known to have lung cancer. Physicians involved in the care of these patients should familiarize themselves with both of these relatively new nuclear medicine imaging procedures. Both F-18 FDG PET imaging and Tc 99m depreotide SPECT imaging have a high degree of sensitivity, specificity, overall accuracy, and both PPV and NPV in the management of patients with a solitary pulmonary nodule. Nuclear imaging with either of these agents provides a noninvasive, cost-effective method to select patients for aggressive intervention without contributing to increased morbidity. There has not been a direct comparison of these two techniques in terms of their relative role and cost-effectiveness in the management of patients with a solitary pulmonary nodule. Both methods have incremental value over CT imaging in selecting patients with solitary pulmonary nodules either for invasive biopsy or for thoracotomy. To date, only FDG PET has been proved to have additional application in: 1. Improving the staging of patients by identifying or excluding mediastinal disease. Some authors are reluctant at the present time to deny patients an opportunity for curative resection based on the finding of foci of increased metabolism in the mediastinum (characterized by increased FDG activity) because there are occasional false-positive studies. They propose, however, that a negative study justifies a surgical approach (and an opportunity for cure) regardless of the findings on CT. 2. Evaluation of therapy and early detection of recurrence by using FDG PET imaging as a monitoring procedure. Tc 99m depreotide may have a role also in these other clinical indications for imaging in patients with lung carcinoma. It is too soon, however, to know if Tc 99m depreotide SPECT imaging, properly performed, can mimic the success of FDG PET in the detection or exclusion of mediastinal metastases, evaluating the response to therapy, and the early detection of recurrent disease during post-therapeutic monitoring.

Role of nuclear medicine in the evaluation of the solitary pulmonary nodule.

Tomographic imaging with either F-18 fluoro deoxyglucose (FDG) (a nonmetabolizable glucose analog that reflects tumor increased glucose metabolism) or technetium Tc-99m Depreotide (a synthetic peptide that binds with high affinity to cell surface receptors with increased expression on certain tumor cells) provides improved sensitivity and specificity in the differential diagnosis of solitary pulmonary nodules (SPN) compared with noninvasive and some invasive procedures. F-18 FDG requires instrumentation capable of coincident imaging whereas Tc-99m Depreotide can be imaged on standard gamma cameras equipped to perform single photon emission computed tomography (SPECT) imaging. Either technique performs better than CT alone, and both are cost effective on the basis of reducing unnecessary biopsies and thoracotomies in patients with negative studies indicating that the SPN is nonmalignant.

Impact of radiotherapy on normal brain tissue: semi-automated quantification of decrease in perfusion.

PURPOSE: We attempted to ascertain the impact of Co-60 conventional external radiotherapy (cRT) on the perfusion of normal brain tissue in relation to the radiation doses delivered to the tumors in patients with primary brain tumors. MATERIALS AND METHODS: After surgery 18 patients (pts) were due to undergo cRT with a total dose of 5400- 6400 cGy. All the patients had a Tc-99m-HMPAO SPECT study prior to cRT (basal), 15th and 30th days of cRT as well as 1 (in 6 pts), 3 (in 9 pts), and 6 (in 3 pts) months after cRT. For quantitative evaluation, the entire set of transverse slices were divided into 4 regions as frontal, parietal, occipital and temporal regions by means of a computer software program. Semi-automated quantification was performed on a total of 1392 regions in 87 studies to determine left to right ratios. An interregional difference of at least 10% was considered abnormal. RESULTS: After elimination of tumor sites, 80 normal brain regions showed decreased perfusion after cRT. The percent decrease in perfusion was (mean 22.5+/-9.9) significantly higher in areas irradiated with doses > 3000 cGy (p < 0.05). CONCLUSION: cRT has adverse effects on the perfusion of normal brain tissue for doses > 500 cGy. Our findings justify treating patients with small and limited lesions with stereotactic radiotherapy in order to minimize the adverse effects of cRT on normal tissues.

Positron emission tomography in lymphoma: comparison with computed tomography and Gallium-67 single photon emission computed tomography.

With the advent of positron emission tomography (PET), metabolic imaging has become a reality for tumor staging and monitoring response to therapy in lymphoma. Increased Fluorine-18 fluorodeoxyglucose ([(18)F]FDG) uptake in lymphomas has been well documented in the literature; it is based upon elevated glycolysis and longer residence time of FDG in malignant cells compared to most normal tissues. This suggests that in tumor staging, FDG-PET may be more sensitive and specific than the anatomic imaging modalities. Computed tomography (CT) is the standard imaging modality for the staging and restaging of lymphoma, and Gallium-67 ((67)Ga) scintigraphy has played an important role in monitoring response to therapy and follow-up of patients. Published results suggest that FDG-PET is superior to (67)Ga imaging and may be equal or superior to CT for the detection of nodal as well as extranodal involvement in lymphoma.

Cerebral blood flow changes in patients with conversion disorder.

We evaluated regional cerebral blood flow in five patients with conversion disorder (three females, two males, mean age+/-S.D.: 29.8+/-9.5 years) with astasia-abasia. The patients underwent single photon emission computed tomography after the injection of 555 MBq of [99mTc]hexamethylpropyleneamine oxime. Uptake ratios between areas of decreased perfusion and normal brain regions were considered significantly decreased when there was a change > or = 10%. Four of the five patients had left temporal and one patient had left parietal perfusion decreases. Uptake ratios ranged from 0.72 to 0.88 (mean+/-S.D.: 0.81+/-0.08). Our findings suggest that alterations in regional brain perfusion may accompany conversion symptoms. Functional imaging may therefore offer a means of elucidating the neural correlates of conversion disorder.

P-glycoprotein expression by technetium-99m-MIBI scintigraphy in hematologic malignancy.

UNLABELLED: Our aim was to ascertain the relationship between the degree of 99mTc-MIBI uptake and the level of p-glycoprotein (Pgp) expression determined by flow cytometry and reverse transcription-polymerase chain reaction (RT-PCR) techniques in patients with hematologic malignancy. METHODS: A total of 21 samples (19 patients) were evaluated. Two patients had repeat studies after therapy. Thirteen samples were studied at the time of initial diagnosis and 8 during relapse after therapy. After MIBI imaging, either bone marrow aspiration or peripheral blood was obtained for flow cytometric and RT-PCR analyses. Flow cytometry was performed using two different antibodies. After the injection of 555 MBq MIBI, whole-body and pelvic spot images were acquired using a dual-head gamma camera. The uptake in the bone marrow was evaluated against the background (adjacent soft tissue) by both qualitative (scoring system) and quantitative (tm/bkg ratios) analyses. RESULTS: For flow cytometry, the limit for Pgp overexpression was set at >15% Pgp-positive mononuclear bone marrow or peripheral blood cells. There was an inverse correlation between the levels of Pgp and MIBI imaging using both the qualitative (scoring system) and quantitative (tm/bkg ratios) analyses (p = 0.022). Mean values were statistically different between Pgp+ and Pgp- groups for both qualitative and quantitative analyses (p = 0.009 and 0.024, respectively). For RT-PCR, there was statistical support toward a difference in the mean values between Pgp+ and Pgp- groups by qualitative analysis (p = 0.061); however, no statistical difference was found between these two groups by quantitative analysis (p = 0.179). CONCLUSION: Based on the strong correlation between the imaging and flow cytometry and a statistical support toward the correlation between the imaging and RT-PCR, MIBI imaging may be used for the in vivo detection of Pgp in patients with hematologic malignancy.

Influence of the heterogeneity of P-glycoprotein expression on technetium-99m-MIBI uptake in breast cancer.

UNLABELLED: We prospectively studied a total of 30 patients with breast cancer to evaluate the relationship between the degree of accumulation of 99mTc-sestamibi (MIBI) and the heterogeneity of p-glycoprotein expression in tumor tissues. METHODS: Twenty patients during initial presentation and 10 patients during post-therapy evaluation underwent contemporaneous 99mTc-MIBI imaging and surgery or biopsy. Immunohistochemical studies were performed on multiple nonconsecutive sections of the same tumor using a p-glycoprotein-specific monoclonal antibody, JSB-1. Tumor-to-background (T/B) ratios were correlated with the level and heterogeneity of p-glycoprotein expression determined by immunohistochemical studies. RESULTS: The T/B ratios were lower for those tumors with strong p-glycoprotein expression (Group 1) than those with strong-to-weak expression (Group 2) or those with weak-to-no expression (Group 3) (1.32 +/- 0.19 and 1.85 +/- 0.56 and 2.86 +/- 1.06, respectively). There was statistically significant difference in T/B ratios between all 3 groups (p < 0.005). Although T/B ratios for Group 1 and Group 3 were clearly distinct from one another with no overlapping values, the values for Group 2 overlapped with those of Group 1 and Group 3. When we evaluated the entire patient group with excluding those with strong-to-weak expression, although the p value remained the same (p < 0.001), we obtained a stronger correlation between T/B ratios and p-glycoprotein expression (r = 0.808 versus 0.735). CONCLUSION: Due to the heterogeneous expression of p-glycoprotein, both immunohistochemistry and 99mTc-MIBI scintigraphy may yield confounding results by contrasting with one another if the presence or absence of p-glycoprotein is not extensively explored. Although our data confirmed that 99mTc-MIBI imaging is useful in the determination of the presence of multidrug resistance in patients with breast cancer, the issue of heterogeneous expression of the antigen should be further investigated when unexpected results are obtained.

Association of tumor washout rates and accumulation of technetium-99m-MIBI with expression of P-glycoprotein in lung cancer.

UNLABELLED: In a prospective study, we correlated the washout rates of 99mTc-sestamibi (MIBI) and the degree of MIBI accumulation with the expression of P-glycoprotein (Pgp) in tumor tissues in a total of 46 patients with lung cancer. METHODS: All patients underwent early (30 min) and delayed (3 hr) MIBI imaging and bronchoscopic biopsy before initiation of chemo- or radiotherapy. The interval between biopsy and imaging varied between 2 and 10 days. All patients had radiologically detectable tumors. Immunohistochemical studies were performed on paraffin sections using a monoclonal antibody, JSB-1, developed against the internal epitope of Pgp. Normal tissue and tumor washout rates and tumor-to-background ratios were correlated with the level of Pgp expression. RESULTS: There was an inverse correlation between tumor-to-background ratios and the density of Pgp (p = 0.001), whereas there was no appreciable correlation between tumor washout rates of MIBI and the level of Pgp expression (p = 0.414). CONCLUSION: The current data strongly suggest that, although the reduced ability for the tumors to accumulate MIBI correlates well with the increased levels of Pgp expression, tumor washout rates of MIBI do not correlate with the density of Pgp in tumor tissues. Our results also warrant additional research for correlating immunohistological and imaging findings with messenger RNA levels determined by polymerase chain reaction and flow cytometry.

Clinical validation of the influence of P-glycoprotein on technetium-99m-sestamibi uptake in malignant tumors.

UNLABELLED: We prospectively studied 48 patients with either breast cancer (30 patients) or lung cancer (18 patients) to ascertain the relationship between the degree of accumulation of 99mTc-sestamibi and the expression of p-glycoprotein in tumor tissues. METHODS: During initial presentation (37 patients) or post-therapy evaluation (11 patients), the patients underwent contemporaneous 99mTc-sestamibi imaging and biopsy (30 patients) or surgery (18 patients). The interval between surgery/biopsy and imaging varied between 3 and 15 days. All patients had radiologically detectable tumors. Immunohistochemical studies were performed on paraffin sections using a monoclonal antibody, JSB-1, developed against the internal epitope of p-glycoprotein. Tumor-to-background ratios were correlated with the level of p-glycoprotein expression determined by immunohistochemical studies. RESULTS: Our results showed an inverse correlation between the tumor-to-background ratios of 99mTc-sestamibi and the density of p-glycoprotein expression in tumor tissues. The values for the tumor-to-background ratios were significantly lower for those tumors expressing p-glycoprotein at high levels than those with scattered and no expression (p < 0.01 and p < 0.001, respectively). CONCLUSION: Although our results warrant further studies at the molecular level using PCR techniques after the extraction of mRNA, our data strongly suggest that 99mTc-sestamibi imaging is useful to noninvasively determine the presence of multidrug resistance in patients with malignant tumors.

Monitoring response to therapy with thallium-201 and technetium-99m-sestamibi SPECT in nasopharyngeal carcinoma.

UNLABELLED: This study prospectively assessed the value of 201Tl and 99mTc-sestamibi (MIBI) SPECT in monitoring disease regression/progression as compared with MRI findings in patients with nasopharyngeal carcinoma (NPC) having radiotherapy with or without chemotherapy. METHODS: Eighteen patients (age range 15-78 yr, mean 45 yr) had consecutive SPECT imaging using a dual-head gamma camera after the injection of 111 MBq 201Tl and 555 MBq MIBI before therapy and at 3 mo and 6 mo after completion of therapy. A total of 106 SPECT studies was correlated with contemporaneous MRI studies. Tumor-to-background ratios were obtained on coronal slices. Visually detectable lesions in the region of the nasopharynx and cervical lymph nodes were considered positive for residual disease. The gold standard for the presence of disease was the combination of repeat MRI scans, endoscopic examination and clinical evaluation performed 12-15 mo after completion of therapy. RESULTS: MIBI-SPECT proved superior to both 201Tl SPECT and MRI after 3 or 6 mo follow-up in predicting complete response. Accuracy rates in the detection of residual disease in the nasopharynx are 39%, 72% and 89% for MRI, 201Tl and MIBI, respectively, for the 3-mo evaluation; 71%, 71% and 94% for MRI, 201Tl and MIBI, respectively, for the 6-mo evaluation. CONCLUSION: MIBI SPECT could be used as a screening test in predicting response to therapy in patients with NPC.