Hepatic and Pulmonary Vasoactive Response Triggered by Potentially Hazardous Chemicals After Passing Through the Gut Mucosa

<b>Background/Objectives</b>: In a previous study, we observed significantly prolonged hepatic and pulmonary first-pass transit times (TTs) for ^99mTc-pertechnetate absorbed through the colorectal mucosa during per-rectal portal scintigraphy (PRPS). This decrease in radiotracer flow velocity was not seen when ^99mTc-pertechnetate was administered into the spleen during trans-splenic portal scintigraphy or injected intravenously in radionuclide angiocardiography. We hypothesized that ^99mTc-pertechnetate, an artificial compound, is recognized during colorectal absorption as a potentially hazardous chemical (PHC), with its hepatic and pulmonary slowdown aiding elimination. A similar sudden decrease in portal flow occurs during early metastasis of colorectal cancer (CRC), as shown by a pathological rise in the hepatic perfusion index. We aimed to study the hepatic and pulmonary vasoactive responses triggered by PHCs after they pass through the gut mucosa and evaluate the potential activation of this mechanism in early CRC metastasis. <b>Methods</b>: We measured transit times to determine whether hepatic and pulmonary vasoconstriction occur in response to radiotracers administered at different sites. We performed PRPS with in vivo ^99mTc-labelled RBC to evaluate the liver transit time (LTT) and right heart to liver circulation time (RHLT). Liver angioscintigraphy (LAS) was used to assess RHLT following the intravenous injection of ^99mTc-pertechnetate and ^99mTc-HDP (hydroxyethylene-diphosphate). Lower rectum transmucosal dynamic scintigraphy (LR-TMDS) was conducted to measure RHLT of ^99mTc-pertechnetate delivered into the lower rectum submucosa. LAS was performed to assess LTT for ^99mTc-HDP intravenously injected and delivered to the gut mucosa via arterial flow. <b>Results:</b> In healthy volunteers, PRPS showed notably increased LTT, ranging from 23.5 to 25.5 s, and RHLT (between 39.5 and 42.5 s) for in vivo ^99mTc-labelled RBC. Significantly lower RHLT values ranging from 9 to 13.5 were observed for ^99mTc-pertechnetate and ^99mTc-HDP administered intravenously during LAS, as well as for ^99mTc-pertechnetate at LR-TMDS (between 12 and 15 s). The LTT assessed at LAS for ^99mTc-HDP ranged from 22 to 27 s. <b>Conclusions</b>: An intense vasoconstriction occurs in the liver and lungs in response to substances recognized by the body as PHCs when they pass through the gut mucosa, aiding their elimination.