Optimized procedure of real-time systemic leakage monitoring during isolated limb perfusion using a hand held gamma probe and 99mTc-HSA.

Abstract

Isolated limb perfusion (ILP) therapy using a combination of tumour necrosis factor alpha (TNF) and cytostatic agents in hyperthermic conditions has proven to be effective in treating cancers limited to limbs or to a single organ such as the liver. A critical step for ILP is the accurate and real-time monitoring of that TNF toxic effects become relevant when overcoming the 10% limit of the 'effective' therapeutic dose administered during ILP. The most diffuse procedure for systemic leakage monitoring is based on the utilization of human soluble serum albumin (HSA) labelled with 131I and an external scintillation detector. In order to overcome some drawbacks connected with the properties of 131I, we developed a new procedure based on the utilization of HSA labelled with 99mTc in combination with a hand held gamma probe used as a detector. Our procedure consists of the following steps: (1) a 99mTc-HSA dose standardized as 0.5 MBq x kg(-1) body weight is injected into the ILP circuit before TNF administration; (2) a hand held gamma probe is placed over the pre-cordial area in a zone pre-marked on the patient's skin during a simulation test; (3) 48-72 h before ILP, a simulation test is obtained using a 99mTc-HSA dose corresponding to 10% of the dose calculated for ILP (i.e., 0.05 MBq x kg(-1) body weight); (4) during the simulation test the maximum count-rate zone detected on the pre-cordial area is marked on patient's skin; (5) a 60 min time-activity curve corresponding to the circulating 99mTc-HSA radioactivity effective decay is calculated and fitted; and (6) this time-activity curve is used to compensate for the leakage systemic counting observed during ILP. In order to compare the external, probe counting with the circulating radioactivity, in the first 10 patients from a total series of 43 treated patients, the results of external, probe monitoring were compared with the results of patient blood and perfusion circuit samples taken simultaneously every 5 min and measured by a laboratory gamma counter placed in the operating theatre. A good correlation was found between the two methods (R2 = 0.965, P < 0.01). It is concluded that the proposed procedure, based on the combination of 99mTc-HSA as the radiotracer and a hand held gamma probe as the detector, appears to be technically simple and accurate enough in the real-time monitoring of perfusion leakage in ILP cancer therapy. Moreover, using 99mTc-HSA as the radiotracer, the risk of radioactive contamination is significantly lower in comparison with 131I-HSA.