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.

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.

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.

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.

Phase I radioimmunotherapy trial with iodine-131-CC49 in metastatic colon carcinoma.

UNLABELLED: CC49 is a murine monoclonal antibody (MAb) that reacts against the TAG-72 antigen. We carried out a Phase I study with escalating doses of 131I-CC49 in patients with advanced colorectal cancer expressing the TAG-72 antigen to determine the dose-limiting toxicity and therapeutic efficacy, if any, of the radioimmunoconjugate. METHODS: Twenty-four patients with TAG-72- expressing colorectal cancer were treated with escalating doses of 131I-CC49 starting at 15 mCi/m2 and going up to 90 mCi/m2 of 131I labeled to 20 mg MAb CC49. Patients were selected if TAG-72 was expressed in > or = 50% of cells in previously resected tumor and at least one metastasis was demonstratable on standard imaging such as CT. All patients had failed conventional chemotherapy and had not received prior radiotherapy or murine MAb. Patients were under radiation isolation precautions until whole-body radioactivity decreased to < or = 5 mR/hr at 1 m. Whole-body scintigrams were obtained prior to discharge and 1 and 2 wk after infusion in all patients. SPECT imaging was carried out at least once in all patients. RESULTS: All patients had excellent targeting of radioactivity to known tumor sites. There was no nonhematologic toxicity. Hematologic toxicity was more pronounced in those patients who had received extensive prior chemotherapy. There were no major responses. All patients developed an immune response (HAMA) within 4 wk of therapy. CONCLUSION: Radioimmunotherapy with 131I-CC49 is safe and there is significant therapeutic efficacy in this Phase I trial at the doses studied. There is excellent targeting of radioactivity to antigen-positive tumors. Dose-limiting toxicity is hematopoietic, with the maximum tolerated dose in this group of heavily pretreated patients being 75 mCi/m2.

Validation of gallium-67-citrate single-photon emission computed tomography in biopsy-confirmed residual Hodgkin's disease in the mediastinum.

In a retrospective study of a series of 30 adult patients during restaging of Hodgkin's disease after therapy, computed tomography (CT) and biopsy results were correlated with 67Ga SPECT in order to determine the value of SPECT imaging in monitoring recurrent mediastinal Hodgkin's disease. SPECT had an overall accuracy of 93% (28/30) and correctly identified active disease in 24 of 25, 96% of histopathologically proven recurrent Hodgkin's disease. Thus in this post-therapy setting, we have confirmed the high sensitivity of 67GA SPECT scans in patients selected for biopsy. Gallium-67 may prove particularly useful in detecting residual disease activity in patients in whom biopsy was positive but the interpretations of the CT scans were uncertain in regard to presence of tumors [8/30 (27%)]. In this group of patients, we found SPECT particularly helpful. A larger prospective series is under way to assess this possibility.

Comparison of technetium-99m-MIBI and thallium-201-chloride uptake in primary thyroid lymphoma.

A case of primary thyroid lymphoma demonstrating uptake of 99mTc-hexakis-2-methoxy isobutyl isonitrile (MIBI) is presented. The 99mTc-MIBI image more clearly delineated the extent of tumor as demonstrated on CT compared to 201Tl-chloride and [99mTc]pertechnetate images. Following two courses of chemotherapy, repeat radionuclide studies and CT scan showed complete resolution of the thyroid tumor. Technetium-99m-MIBI may be useful in the assessment of disease activity and monitoring response to treatment in patients with lymphoma.

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.

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.

Pre- and post-therapy thallium-201 and technetium-99m-sestamibi SPECT in nasopharyngeal carcinoma.

UNLABELLED: We prospectively studied the diagnostic potential of 201Tl and 99mTc-sestamibi (MIBI) SPECT for evaluating the extent of primary disease and differentiating residual/recurrent disease from post-therapy changes in patients with nasopharyngeal carcinoma (NPC). METHODS: Fifty patients (20 initial presentation, 30 post-therapy evaluation) underwent 201Tl and MIBI imaging. The findings were correlated with CT/MRI results. Tumor-to-background ratios were obtained. Biopsy confirmation (14 patients) and/or 6-12 mo clinical follow-up data (16 patients) were available in the post-therapy group. RESULTS: All primary disease sites were accurately detected by both imaging studies in the pretherapy group. However, MIBI-SPECT was superior to 201Tl SPECT (p = 0.0057) in detecting regional metastases (sensitivities of 95% versus 68%). In the post-therapy group, MIBI and 201Tl imaging were true-positive in 14 of 16 patients with proven residual/recurrent. In 17 patients who had no evidence of residual/recurrent tumor. CT/MRI was false-positive in 13 when MIBI and 201Tl imaging were true-negative in 10 and false positive in 3. MIBI, 201Tl and CT/MRI had sensitivities of 87.5%, 87.5%, 100%, specificities of 82.4%, 76.5%, 23.5% and accuracies of 85%, 82%, 61%, respectively. Tumor-to-background ratios were < or = 1.5 in all false-positive cases except one. CONCLUSION: MIBI-SPECT proves more accurate than 201Tl SPECT in detecting regional metastases at initial presentation. MIBI and 201Tl imaging have higher specificity and accuracy than CT/MRI and MIBI-SPECT is slightly more specific than 201Tl SPECT in differentiating residual/ recurrent disease from post-therapy changes in patients with NPC.

Speech-related visualization of laryngeal muscles with fluorine-18-FDG.

UNLABELLED: This study describes the physiological uptake of 18F-fluoro-2-deoxyglucose (FDG) by the laryngeal muscles secondary to activation of the patient's vocal folds and related laryngeal muscles during speech. METHODS: Twenty-four patients undergoing routine PET scans were randomized into two groups to ascertain the relationship between FDG uptake in the laryngeal region and speech. One group was assigned to talk and the other group remained silent during the injection and uptake period of FDG. RESULTS: FDG uptake in the laryngeal muscles in the scans was correlated with speech. Patients who spoke continually during the uptake period had high-grade FDG uptake, those who spoke intermittently had low-grade uptake and those who remained silent had no detectable increase in FDG uptake in the region of the larynx. CONCLUSION: The relationship between the degree of laryngeal muscle uptake and speech provides useful information to allow differentiation of physiological from pathological uptake in the neck.

The diagnosis of renovascular hypertension with technetium-99m-ethylenedicysteine captopril scintigraphy.

RATIONALE AND OBJECTIVES: The authors present preliminary findings on the diagnosis of renovascular hypertension with technetium-99m-ethylenedicysteine (99mTc-EC). METHODS: Thirty-nine patients referred to the nuclear medicine department with clinical evidence of renovascular hypertension were included in the study. Baseline and captopril scintigraphies were done on separate days after the injection of 185 MBq of 99mTc-EC. All patients had angiographic correlation and 9 patients were shown to have renal artery stenosis. RESULTS: Quantitative analysis of the data showed no significant changes of perfusion index (PI), split renal function (SRF), and effective renal plasma flow (ERPF) values between pre- and postcaptopril studies in patients with significant renal artery stenosis (P > 0.05). Baseline and postcaptopril values for PI, SRF, and ERPF were measured as 128 +/- 21 and 116 +/- 12 mL/minute, 47 +/- 1 and 50 +/- 2 mL/minute, and 250 +/- 18 and 231 +/- 20 mL/minute, respectively. However, time to maximum activity (Tmax), time to half maximum activity (T 1/2), time to two thirds of maximum activity (T 2/3), and residual cortical activity (RCA) values showed marked changes with a rising renogram curve (P < 0.05). Baseline and postcaptopril values for Tmax, T 1/2, T 2/3, and RCA were measured as 3.1 +/- 0.1 and 20.2 +/- 1 minute, 5.4 +/- 0.4 and 45.4 +/- 3.1 minutes, 3.1 +/- 0.2 and 33.7 +/- 4.1 minutes, and 27 +/- 4 and 215 +/- 34 minutes, respectively. All scintigraphic studies showed good correlation with angiography and no false-positive or false-negative results were observed. CONCLUSIONS: This preliminary study demonstrates that 99mTc-EC has good potential for the diagnosis of renovascular hypertension and that a single diagnostic criteria, specifically a rising renogram curve, seems adequate. However, the authors' initial results should be confirmed in a broader patient population.

Technetium-99m-ethylenedicysteine in the diagnosis and follow-up of renovascular hypertension.

Technetium-99m-ethylenedicysteine (99mTc-EC) captopril scintigraphy performed in a patient with severe hypertension revealed increased parenchymal retention in the left kidney, suggesting renal artery stenosis. After angiographic confirmation of renal artery stenosis, percutaneous transluminal angioplasty (PTA) was performed on the left renal artery. Captopril scintigraphy after PTA showed normal findings with no evidence of parenchymal retention, consistent with reversal to normal kidney functions. In light of this case of renal artery stenosis, it was concluded that 99mTc-EC can be used successfully as a potential renal agent in the diagnosis and follow-up of renovascular hypertension.

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.

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.

Calculated and TLD-based absorbed dose estimates for I-131-labeled 3F8 monoclonal antibody in a human neuroblastoma xenograft nude mouse model.

Preclinical evaluation of the therapeutic potential of radiolabeled antibodies is commonly performed in a xenografted nude mouse model. To assess therapeutic efficacy it is important to estimate the absorbed dose to the tumor and normal tissues of the nude mouse. The current study was designed to accurately measure radiation does to human neuroblastoma xenografts and normal organs in nude mice treated with I-131-labeled 3F8 monoclonal antibody (MoAb) against disialoganglioside GD2 antigen. Absorbed dose estimates were obtained using two different approaches: (1) measurement with teflon-imbedded CaSO4:Dy mini-thermoluminescent dosimeters (TLDs) and (2) calculations using mouse S-factors. The calculated total dose to tumor one week after i.v. injection of the 50 microCi I-131-3F8 MoAb was 604 cGy. The corresponding decay corrected and not corrected TLD measurements were 109 +/- 9 and 48.7 +/- 3.4 cGy respectively. The calculated to TLD-derived dose ratios for tumor ranged from 6.1 at 24 h to 5.5 at 1 week. The light output fading rate was found to depend upon the tissue type within which the TLDs were implanted. The decay rate in tumor, muscle, subcutaneous tissue and in vitro, were 9.5, 5.0, 3.7 and 0.67% per day, respectively. We have demonstrated that the type of tissue in which the TLD was implanted strongly influenced the in vivo decay of light output. Even with decay correction, a significant discrepancy was observed between MIRD-based calculated and CaSO4:Dy mini-TLD measured absorbed doses. Batch dependence, pH of the tumor or other variables associated with TLDs which are not as yet well known may account for this discrepancy.