Intraperitoneal injection

In rodent studies the PET radiopharmaceutical is usually injected manually via tail-vein catheter. However, intraperitoneal injection is more convenient and can be reliable in small rodents, although it can fail, too, for example because of injection into the bowel, urinary bladder, or subcutaneously (Steward et al., 1968; Miner et al., 1969; Arioli & Rossi, 1970; Coria-Avila et al., 2007; Gaines Das & North, 2007; Vines et al., 2011; Turner et al., 2011).

Intraperitoneal injection can be applied in sequential and multi-tracer studies (Wong et al., 2011), with proved reproducibility in [18F]FDG rat studies (Marsteller et al., 2006). Further, for mouse [18F]FDG studies, peritoneal injection has been shown to provide biodistribution that is comparable to tail vein injection results (Fueger et al., 2006; Schiffer et al., 2007) and SUV and Patlak results (Wong et al., 2011) within 60 min after administration.

Initial distribution of intra-peritoneally injected radiopharmaceuticals in animals is slower than after intravenous injection because the radiotracer has to diffuse across the peritoneal membrane into mesenteric vessels which drain into the portal system and liver (Lukas et al., 1971; Wong et al., 2011). A fraction of intraperitoneally injected radiotracer may pass across the diaphragm through small lacunae into the thoracic lymph (Abu-Hijleh et al., 1995). Fluid removal rate from the peritoneal cavity is affected by hydrostatic pressure against the diaphragm and, thus, posture (Barrett et al., 1997). The slower kinetics may require prolonged scan times, and may affect the SUV compared to intravenous injection (Schiffer et al., 2007). The passage through portal system may prevent the use of radiopharmaceuticals which are rapidly metabolized in the liver.

Arterial plasma input function measurement is easier and possibly more reliable after peritoneal injection than after intravenous injection because the slower distribution of the radiopharmaceuticals requires less frequent plasma sampling, and dispersion and delay correction may not be needed (Wong et al., 2011). On the other hand, image-derived input function estimation methods may not perform as well, because it is more difficult to kinetically separate input function from tissue concentration curves. Also metabolite fractions may be higher and more variable after intraperitoneal injection. Neither arterial or venous input function is not appropriate for quantitative analysis of the liver, because intraperitoneally injected radiotracer has already passed through the liver before appearing in the systemic circulation.

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Abu-Hijleh MF, Habbal OA, Moqattash ST. The role of the diaphragm in lymphatic absorption from the peritoneal cavity. J Anat. 1995; 186(Pt 3): 453-467. PMID: 7559120.

Fueger BJ, Czernin J, Hildebrandt I, Tran C, Halpern BS, Stout D, Phelps ME, Weber WA. Impact of animal handling on the results of 18F-FDG PET studies in mice. J Nucl Med. 2006; 47: 999-1006. PMID: 16741310.

Higashi T, Fisher SJ, Nakada K, Romain DJ, Wahl RL. Is enteral administration of fluorine-18-fluorodeoxyglucose (F-18 FDG) a palatable alternative to IV injection? Preclinical evaluation in normal rodents. Nucl Med Biol. 2002; 29: 363-373. doi: 10.1016/S0969-8051(01)00312-2.

Lukas G, Brindle SD, Greengard P. The route of absorption of intraperitoneally administered compounds. J Pharmacol Exp Ther. 1971; 178(3): 562-564. PMID: 5571904.

Marsteller DA, Barmarich-Marsteller NC, Fowler JS, Schiffer WK, Alexoff DL, Rubins DJ, Dewey SL. Reproducibility of intraperitoneal 2-deoxy-2-[18F]-fluoro-D-glucose cerebral uptake in rodents through time. Nucl Med Biol. 2006; 33: 71-79. doi: 10.1016/j.nucmedbio.2005.09.003.

Schiffer WK, Mirrione MM, Dewey SL. Optimizing experimental protocols for quantitative behavioral imaging with 18F-FDG in rodents. J Nucl Med. 2007; 48: 277-287. PMID: 17268026.

Wong K-P, Sha W, Zhang X, Huang S-C. Effects of administration route, dietary condition, and blood glucose level on kinetics and uptake of 18F-FDG in mice. J Nucl Med. 2011: 52: 800-807. doi: 10.2967/jnumed.110.085092.

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Updated at: 2019-02-12
Created at: 2011-05-04
Written by: Vesa Oikonen, Anne Roivainen