Intraarterial

This approach has been used primarily in Japan to treat patients with malignant, inoperable hepatic cancer. Mitomycin C contained in albumin microspheres was administered to patients (122) by percutaneous intraarterial catheterization. Tumor reduction was seen in over 68% of the cases. By contrast, the control group, receiving infusion therapy, had a poorer response. Survival times were also greater for patients receiving the microspheres. 

Intraarterial infusion of microspheres containing adriamycin was used for the local treatment of breast cancer and recurrent breast cancer with liver metastases (123). A reduction in tumor size was noted when the microspheres were injected into the internal and lateral thoracic arteries for treatment of the primary tumor. However, hepatic artery injection for liver metastases resulted in improvement in only one of three patients treated. 

In reviewing intraarterial infusion of microencapsulated anticancer agents and its clinical applications, Nemoto (124) concluded that this mode of treatment can be used for a wide variety of tumors, providing remarkable therapeutic effects with minimal systemic toxicity. However, 25% of the treated tumors failed to respond, which was thought to be attributable to either inadequate catheterization, inadequate dose relative to tumor size, insufficient tumor vascularity, low drug sensitivity, or a combination of these factors. More carefully designed studies will be necessary before this technique is likely to meet with widespread acceptance. 

Kidwell CS, Saver JL, Starkman S, Duckwiler G, Jahan R, Vespa P, Villablanca JP, Liebeskind DS, Gobin YP, Vinuela F, Alger JR. Late secondary ischemic injury in patients receiving intraarterial thrombolysis. Ann Neurol 2002 52 698-703. 

The effectiveness of catheter-based intra-arterial therapy to remove residual thrombus after IV rt-PA treatment is being tested in the Interventional Management of Stroke study (IMS-Ill). This study will randomize patients to 0.6 mg/kg IV rt-PA, followed by angiography with additional intra-arterial therapy as indicated, or IV full-dose rt-PA (0.9 mg/kg). A nonrandomized safety study suggested that intraarterial therapy, after 0.6 mg/kg IV rt-PA, could be accomphshed with acceptable rates of sICH. ° ... 

TABLE 4.2 Management of Symptomatic Intracerebral Hemorrhage after Intraarterial Thrombolysis. 

Barnwell SL, Clark WM, Nguyen TT, O Neill OR, Wynn ML, Coull BM. Safety and efficacy of delayed intraarterial urokinase therapy with mechanical clot disruption for thromboembolic stroke. Am J Neuroradiol 1994 15 1817-1822. 

Lisboa RC, Jovanovic BD, Alberts MJ. Analysis of the safety and efficacy of intraarterial thrombol3ftic therapy in ischemic stroke. Stroke 2002 33 2866-2871. 

Zeumer H, Hacke W, Ringelstein EB. Local intraarterial thrombolysis in vertebrobasilar thromboembolic disease. Am J Neuroradiol 1983 4 401 04. 

Keris V, Rudnicka S, Vorona V, Enina G, Tilgale B, Fricbergs J. Combined intraarterial/ intravenous thrombolysis for acute ischemic stroke. Am JNeuroradiol 2001 22 352-358. 

Lee DH, Jo KD, Kim HG, Choi SJ, Jung SM, R)oi DS, Park MS. Local intraarterial urokinase thrombolysis of acute ischemic stroke with or without intravenous abciximab a pilot study. J Vase Interv Radiol 2002 13 769-774. 

Lutsep HL, Clark WM, Nesbit GM, Kuether TA, BamweU SL. Intraarterial suction thrombectomy in acute stroke. Am J Neuroradiol 2002 23 783-786. 

Marinov MB, Harbaugh KS, Hoopes PJ, Pikus HI, Harbaugh RE. Neuroprotective effects of preischemia intraarterial magnesium sulfate in reversible focal cerebral ischemia. J Neurosurg 1996 85 117-124. 

Initial tests in the rat revealed a high degree of tissue compatibility of Dat-Tyr-Hex derived polymers. More detailed tests are now in progress. In addition, tyrosine derived polymers are currently being evaluated in the formulation of an intracranial controlled release device for the release of dopamine, in the design of an intraarterial stent (to prevent the restenosis of coronary arteries after balloon angioplasty), and in the development of orthopedic implants. The use of tyrosine derived polymers in these applications will provide additional data on the biocompatibility of these polymers. 

C. Espadas-Torre and M.E. Meyerhoff, Thrombogenic properties of untreated and poly(ethylene oxide)-modified polymeric matrices useful for preparing intraarterial ion-selective electrodes. Anal. Chem. 67, 3108-3114 (1995). 

Intravenous or intraarterial injection, fetal lambs 80% through gestation (120 days), NaCN, 50-400 pg... 

Time to depurate or biotransform 50% of accumulated PAHs (Tb 1/2) varied widely. Tb 1/2 values for Daphnia pulex and all PAH compounds studied ranged between 0.4 and 0.5 h (Southworth et al. 1978). In rainbow trout given an intraarterial injection of 10 mg/kg BW of 2-methylnaphtha-lene, fluorene, or pyrene, the Tb 1/2 values ranged between 9.6 and 12.8 h when route of exposure was intragastric and doses were 50 mg/kg BW, there was negligible uptake (Kennedy and Law 1990). For marine copepods and naphthalene, a Tb 1/2 of about 36 h was recorded (Neff 1982a). 

Coronary perfusion pressure should be assessed in patients for whom intraarterial monitoring is in place. 

The parenteral routes include three major ones IV (intravenous), IM (intramuscular), and SC (subcutaneous) and a number of minor routes (such as intraarterial) that are not considered here. Administration by the parenteral routes raises a number of special safety concerns in addition to the usual systemic safety questions. These include irritation (vascular, muscular, or subcutaneous), pyrogenicity, blood compatibility, and sterility (Avis, 1985 Ballard, 1968). The background of each of these, along with the underlying mechanisms and factors that influence the level of occurrence of such an effect, are discussed in Chapter 11. 

The need for a rapid onset of action (and/or clearance) usually requires that an IV route be used, although at a certain stage of cardiopulmonary resuscitation (for example), the need for an even more rapid effect may require the use of an intracardiac injection. The required site of action may influence the choice of route of administration (e.g., certain radiopaque dyes are given intraarterially near the site being evaluated streptokinase is sometimes injected experimentally into the... 

Quantitative measurement of diffusional uptake and carrier-mediated transport of nutrients and drugs in experimental animals was greatly facilitated with the introduction of Olden dorfs brain uptake index (BUI) [42].Test and reference tracers are injected as an intraarterial bolus into the carotid artery of the anaesthetized animal. After 5 s the animal is killed and the brain is removed for radioactivity counting. This method measures the ratio of the unidirectional brain extraction, E, of the test substance and of the reference ([ H]-water, [ " C]-butanol), which are labelled with different isotopes, during a single passage through the brain capillary bed ... 

In an effort to overcome the lack of solubility, poor penetration across the blood-brain barrier and decreased delivery of conventional systemic agents by a compromised intratumoral blood supply, several studies have evaluated various combinations of BCNU alone or with other agents delivered intraarterally. Unfortunately, response rates and median survival times observed in patients treated with intraarterial chemotherapy have not been significantly different than those seen in patients treated with standard intravenous nitrosurea-containing regimens, while increased rates of toxicity such as leukoen-cephalopathy, retinal injury, edema, myelosuppression, sepsis, and thrombotic complications have been noted (40-46). 

Stewart DJ, Grahovac Z, Hugenholtz H, et al. Feasibility study of intraarterial vs intravenous cisplatin, BCNU, and teniposide combined with systemic cisplatin, teniposide, cytosine arabinoside, glycerol and mannitol in the treatment of primary and metastatic brain tumors. J Neurooncol 1993 17(l) 71-79. 

Kleinschmidt-DeMastersBK,Geier JM. Pathology of high-dose intraarterial BCNU. Surg Neurol 1989 31(6) 435 443. 

Stewart DJ, Grahovac Z, Hugenholtz H, Russell N, Richard M, Benoit B. Combined intraarterial and systemic chemotherapy for intracerebral tumors. Neurosurgery 1987 2 207-214. 

West CR, Avellanosa AM, Barua NR, Patel A, Hong CL Intraarterial l,3-bis(2-chloroethyl)-l-nitrosourea (BCNU) and systemic chemotherapy for malignant gliomas a follow-up study. Neurosurgery 1983 13(4)420426. 

Lehane DE, Bryan RN, Horowitz B, et al. Intraarterial cis-platinum chemotherapy for patients with primary and metastatic brain tumors. Cancer Drug Deliv 1983 l(l) 69-77. 

The radiological effects of thorium were examined by testing isotopes with shorter radioactive half-lives than thorium-232. No increased mortality was found in mice injected intravenously with 0.5 ml Thorotrast (3660 mg thorium-232/kg) (Guimaraes et al. 1955), or in dogs after intraarterial injection of thorium nitrate (476 mg thorium-232/kg), but the LDsofor intravenously- injected thorium-230 in rats was 42.7 mg thorium/kg (Boone et al. 1958). The toxic effects of thorium were attributed to radiological and not chemical effects (Boone et al. 1958). 

In addition to the usual intravenous or oral routes, some anticancer agents have been administered by regional intraarterial perfusion to increase drug delivery to the tumor itself and at the same time diminish systemic toxicity. Thus, patients with metastatic carcinomas of the liver and little or no disease elsewhere (a common occurrence in colorectal cancer) can be treated with a continuous infusion of fluorouracil or floxuridine through a catheter implanted in the hepatic artery. 

Streptozocin is not well absorbed from the gastrointestinal tract and must be administered intravenously or intraarterially. In preclinical studies, the plasma half-life was 5 to 10 minutes. 

Peripheral vascular diseases Infusion or intraarterial injection of prostacyclin (PGI ) improves potency of blood vessels in certain peripheral vascular diseases. Infusion of PGI can also reduce the infarct size in immediate postmyocardial infarction period. 

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