title: Intraperitoneal injection is not always a suitable alternative to intravenous injection for radiotherapy.
abstract: Abstract Intraperitoneal (IP) injection is frequently reported to be as effective as intravenous (IV) injection. Because it allows administering a larger volume with more radioactivity, we have investigated this route and the possibility of using it to circumvent the volume constraint we earlier experienced with pretargeting radiotherapy. Using (99m)Tc as the label, the pharmacokinetics (PK) of the cMORF effector (a DNA analogue) was evaluated after IP or IV injection in normal mice by necropsy and SPECT/CT imaging. In another experiment, nude mice bearing tumors were used and they received MORF-CC49 pretargeting antibody IV 2 days earlier than labeled cMORF IV or IP. Tumor accumulations of cMORF were measured at 6 hours after its injections. The absorbed radiation doses for (188)Re or (90)Y pretargeting were estimated using the (99m)Tc data and a self-absorbed model. Although the absorbed radiation doses to other organs were comparable, the dose to intestines after IP injection was 30-fold higher than IV injection due to the slow entry into the circulation. It had reached such a level as high as the dose to the kidneys that cleared the radioactivity and usually were at the highest level. Nevertheless, the slow entry did not reduce the tumor accumulation. In conclusion, using IP in place of IV led to an unacceptably high absorbed radiation dose to the intestines although the tumor accumulation was not compromised. This effect may be applicable to other radiotherapeutic agents as well.
authors.affiliation: Department of Radiology, University of Massachusetts Medical School , Worcester, Massachusetts.
authors.forename: Shuping
authors.initials: S
authors.lastname: Dou
authors.forename: Miles
authors.initials: M
authors.lastname: Smith
authors.forename: Yuzhen
authors.initials: Y
authors.lastname: Wang
authors.forename: Mary
authors.initials: M
authors.lastname: Rusckowski
authors.forename: Guozheng
authors.initials: G
authors.lastname: Liu
mesh_terms: D000327:Adsorption; D000818:Animals; D000974:Antibodies, Antinuclear; D019540:Area Under Curve; D001682:Biological Availability; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007413:Intestinal Mucosa / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D060172:Morpholinos / Q000008:administration & dosage* / Q000276:immunology / Q000493:pharmacokinetics*; D009369:Neoplasms / Q000378:metabolism* / Q000532:radiotherapy*; D011829:Radiation Dosage; D019275:Radiopharmaceuticals / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D011879:Radiotherapy Dosage; D013667:Technetium / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed
chemical_list: D000974:Antibodies, Antinuclear; D060172:Morpholinos; D019275:Radiopharmaceuticals; D013667:Technetium
keywords: absorbed radiation dose; biodistribution; intraperitoneal; intravenous; pretargeting; tumor accumulation