Continuous leakage monitoring with Sn-medronate - 99mTc - labelled RBC and hand-held gamma-probe during hypertermic isolated limb and lung perfusion

The aim of this study was to analyze the value of continuous leakage monitoring with red blood cells (RBC) labelled with 99mTcmedronate and an external scintillation detector (surgical probe) in patients treated with hyperthermic isolated limb perfusion (ILP) with tumor necrosis factor-alpha (TNF alpha) and melphalan. Systemic hematological and metabolic profiles and tumor response were determined. The mean isotopically measured leakage was 5.8% per hour. The correlation between the monitored systemic activity in the blood by surgical probe and by blood samplings were calculated. A good correlation was observed between the two techniques. Patients with a low leakage rate showed reduced adverse effect. Real time monitoring of the leakage during ILP obtained with this method seems to be in our experience easy, safe and accurate, and serves as a good guide for the effectiveness of isolation during perfusion

Prevention of systemic toxicity in hyperthermic isolated lung perfusion using radioisotopic leakage monitoring

Hyperthermic isolated lung Perfusion (ILuP) is used to deliver high-dose chemotherapy to pulmonary metastases while sparing systemic toxicity. Accurate leakage monitoring is however necessary. This study aimed to verify the accuracy of radionuclide leakage monitoring in patients undergoing ILuP, by comparing this method with serial blood sampling. METHODS: A total of 15 consecutive ILuP procedures were performed on eleven patients affected by lung metastases from soft tissue sarcoma. After establishing isolated perfusion, erythrocytes of systemic blood (SB) were labelled with 0.2 MBq/kg of 99mTc. The baseline SB counting rate (CR) was assessed using a \u3b3-probe. Subsequently, erythrocytes of the circuit blood (CB) were labelled with 2 Mbq/kg of 99mTc. Radioactivity leakage factor (RLF) was continuously measured using a formula, accounting for CR, systemic/circuit activity ratio and total/systemic volume ratio. The TNF-\u3b1 concentration in SB and CB was measured by enzymelinked immunosorbent assay (ELISA) throughout the procedure. RESULTS: RLF averaged 2.3\u2009\ub1\u20091.5%, while the systemic/circuit TNF-\u3b1 ratio was 0.05\u2009\ub1\u20090.12%. These two indices were strictly correlated in all of the procedures (average Rvalue 0.88\u2009\ub1\u20090.07). RLF exceeded 5% during three of 15 procedures, prompting the application of compensatory manoeuvres. ELISA confirmed a marked increase in systemic TNF-\u3b1 levels in these patients (2.6\u2009\ub1\u20093.5\u2009ng/ml). Conversely, patients whose RLF did not exceed the 5% threshold presented a mean TNF-\u3b1 of 0.02\u2009\ub1\u20090.005\u2009ng/ml (p\u2009<\u20090.01). CONCLUSIONS: In patients submitted to ILuP, RLF monitoring is feasible and accurate. Moreover, it grants immediate results, permitting for the adoption of corrective manoeuvres for leakage, thus minimising toxicity

Baseline and ongoing PET-derived factors predict detrimental effect or potential utility of 18F-FDG PET/CT (FDG-PET/CT) performed for surveillance in asymptomatic lymphoma patients in first remission.

Purpose: To identify both clinical and FDG PET/CT-derived factors predicting the occurrence of relapse, or conversely, the likelihood of false positive findings in surveillance FDG-PET/CT studies (PETsv). Methods: The study included 149 asymptomatic patients with Hodgkin's lymphoma (HL) (n = 55) or diffuse large B cell lymphoma (DLBCL) (n = 94) in first remission. PETSv studies were performed 12, 18, 24 and 36 months thereafter. Logistic regression analysis was performed to identify clinical and imaging-derived predictors of either PET-detected relapse or false-positive (FP) results. Tested clinical variables were: 1) age, 2) HL vs. DLBCL, 3) stage of disease, 4) bulky disease, 5) previous radiotherapy. PET/CT-derived variables were: 1) maximum standardized uptake value at baseline, 2) size-incorporated maximum standardized uptake value (SIMaxSUV) at baseline, 3) positive interim PET(PET-2), 4) presence of hot spots likely to be unrelated to the disease in final PET, 5) residual non-FDG avid mass. Results: Accuracy was 88 % for PETsv1, 95 % for PETsv2, 95 % for PETsv3 and 91 % for PETsv4. However, PPV was relatively low in all PETsv. Best predictors of relapse were result of interim PET, HL versus NHL type, SIMaxSUV, age 65 60. Best predictors of FP were previous radiotherapy and hot spots unrelated to the disease in final PET. Conclusions: The present study confirms the need of restricting the use of surveillance PET/CT to patients at high risk of relapse. Information derived from PET/CT performed at baseline (metabolic disease burden), in the course (PET2) and at the end of therapy (unrelated hot spots) can help to select high-risk patients and also to identify patients more likely to present equivocal findings at PETsv

Doxorubicin effect on myocardial metabolism as a prerequisite for subsequent development of cardiac toxicity: A translational18F-FDG PET/CT observation

The present translational study aimed to verify whether serial 18FFDG PET/CT predicts doxorubicin cardiotoxicity. Methods: Fifteen athymic mice were treated intravenously with saline (n = 5) or with 5 or 7.5 mg of doxorubicin per kilogram (n = = each) and underwent dynamic small-animal PET beforehand and afterward to estimate left ventricular (LV) metabolic rate of glucose (MRGlu). Thereafter, we retrospectively identified 69 patients who had been successfully treated with a regimen of doxorubicin, bleomycin, vinblastine, and dacarbazine for Hodgkin disease (HD) and had undergone 4 consecutive18F-FDG PET/CT scans. Volumes of interest were drawn on LV myocardium to quantify mean SUV. All patients were subsequently interviewed by telephone (median follow-up, 30 mo); 36 of them agreed to undergo electrocardiography and transthoracic echocardiography. Results: In mice, LV MRGlu was 17.9 \uc2\ub1 4.4 nmol \ue2\u80\ua2 min21 \uc3\u97 g21 at baseline. Doxorubicin selectively and dose-dependently increased this value in the standard-dose (27.9 \uc2\ub1 9 nmol \uc3\u97 min21 \uc3\u97 g-1, P < 0.05 vs. controls) and high-dose subgroups (37.2 6 7.8 nmol \uc3\u97 min21 \uc3\u97 g-1, P < 0.01 vs. controls, P < 0.05 vs. standard-dose). In HD patients, LV SUV showed a progressive increase during doxorubicin treatment that persisted at follow-up. New-onset cardiac abnormalities appeared in 11 of 36 patients (31%). In these subjects, pretherapy LV SUV was markedly lower with respect to the remaining patients (1.53 \uc2\ub1 0.9 vs. 3.34 \uc2\ub1 2.54, respectively, P < 0.01). Multivariate analysis confirmed the predictive value of baseline LV SUV for subsequent cardiac abnormalities. Conclusion: Doxorubicin dosedependently increases LV MRGlu, particularly in the presence of low baseline18F-FDG uptake. These results imply that low myocardial18F-FDG uptake before the initiation of doxorubicin chemotherapy in HD patients may predict the development of chemotherapy-induced cardiotoxicity, suggesting that prospective clinical trials are warranted to test this hypothesis