Brief intraperitoneal radioimmunotherapy of small peritoneal carcinomatosis using high activities of noninternalizing 125I-labeled monoclonal antibodies.
We assessed the efficiency and toxicity of brief intraperitoneal radioimmunotherapy using high activities of (125)I-labeled monoclonal antibody (mAb) in the treatment of small-volume peritoneal carcinomatosis.


METHODS
Brief intraperitoneal radioimmunotherapy consisted of a 185-MBq (740 MBq/mg) intraperitoneal injection of (125)I-35A7 (an anti-carcinoembryonic antigen mAb) into athymic nude mice 4 d after peritoneal tumor xenografting and, after 1 h, abundant washing of the peritoneal cavity with saline solution to remove unbound radioactivity. Another group of mice received this treatment plus a 37-MBq intravenous injection of (125)I-35A7 on day 7 or 11 after grafting. Control groups received a brief treatment followed by an additional intravenous injection on day 7 of either saline solution or irrelevant (125)I-PX. Tumor growth was monitored by bioluminescence imaging and SPECT/CT, and hematologic toxicity was evaluated by complete blood counts. Survival time was reported, and the mice were sacrificed when the bioluminescence signal reached 4.5 × 10(7) photons/s. The biodistribution of (125)I-35A7 mAb after intravenous or brief treatment was assessed, and the mean absorbed irradiation dose by organs and tumors was calculated using the MIRD formalism.


RESULTS
Mild, transient hematologic toxicity was observed after the brief treatment plus intravenous (125)I-mAb, with no weight loss. Median survival increased from 32 d in the control groups, to 46 d in the brief treatment group, to 66 d in the group additionally receiving intravenous treatment on day 11, to 73 d in the group additionally receiving intravenous treatment on day 7. The brief treatment alone resulted in a 3-fold higher tumor-to-blood uptake ratio than did the standard intravenous treatment, and the mean absorbed irradiation doses by tumors were 11.6 Gy for the brief treatment and 16.7 Gy for the additional intravenous treatment. For healthy tissues other than blood, the mean absorbed irradiation dose did not exceed 1 Gy after brief treatment and 4.2 Gy after intravenous treatment.


CONCLUSIONS
The efficiency, low toxicity, and high tumor-to-healthy tissue uptake ratio associated with brief intraperitoneal (125)I-35A7 radioimmunotherapy suggest that this method can be used in combination with radiation-synergistic drugs in the therapy of small-volume peritoneal carcinomatosis after cytoreductive surgery.
IRCM, Institut de Recherche en Cancérologie de Montpellier, Montpellier, France.
Vincent
V
Boudousq
Stéphanie
S
Ricaud
Véronique
V
Garambois
Caroline
C
Bascoul-Mollevi
Samir
S
Boutaleb
Muriel
M
Busson
François
F
Quenet
Pierre-Emmanuel
PE
Colombo
Manuel
M
Bardiès
Pierre-Olivier
PO
Kotzki
Isabelle
I
Navarro-Teulon
André
A
Pèlegrin
Jean-Pierre
JP
Pouget
D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D001692:Biological Transport; D045744:Cell Line, Tumor; D005260:Female; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D051379:Mice; D010529:Peritoneal Cavity; D010534:Peritoneal Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism / Q000532:radiotherapy*; D016499:Radioimmunotherapy / Q000379:methods*; D011874:Radiometry; D013194:Staining and Labeling; D016019:Survival Analysis; D013997:Time Factors; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed
D000911:Antibodies, Monoclonal; D007457:Iodine Radioisotopes