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Prevention of systemic toxicity in hyperthermic isolated lung perfusion using radioisotopic leakage monitoring
Authors:Francesco Fiz  Giuseppe Villa  Enrico Ferrari  Elena Pomposelli  Silvia Morbelli  Antonella Alloisio
Affiliation:1. Department of Internal Medicine, University of Genoa, Genoa, Italy;2. Nuclear Medicine Unit, Department of Radiology, University of Tübingen, Tübingen, Germany;3. Nuclear Medicine Unit, Department of Health Sciences, University of Genoa, Genoa, Italy;4. Department of Thoracic Surgery, IRCCS San Martino-IST, Genoa, Italy;5. Nuclear Medicine Unit, St. Antonio e Biagio e Cesare Arrigo Hospital, Alessandria, Italy
Abstract:
Rationale: 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 γ-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-α concentration in SB and CB was measured by enzymelinked immunosorbent assay (ELISA) throughout the procedure.

Results: RLF averaged 2.3?±?1.5%, while the systemic/circuit TNF-α ratio was 0.05?±?0.12%. These two indices were strictly correlated in all of the procedures (average Rvalue 0.88?±?0.07). RLF exceeded 5% during three of 15 procedures, prompting the application of compensatory manoeuvres. ELISA confirmed a marked increase in systemic TNF-α levels in these patients (2.6?±?3.5?ng/ml). Conversely, patients whose RLF did not exceed the 5% threshold presented a mean TNF-α of 0.02?±?0.005?ng/ml (p?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.
Keywords:ILuP  radio-guided surgery  TNF-α  clinical trials-isolated limb perfusion  control systems engineering/treatment optimisation
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