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Alternative administration routes in immunoscintigraphy of melanoma and ceasecreting tumors by monoclonal antibodies
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Radiolabeled MonoclonalAntibodies give good imaging sensitivity and its use should be limited to therapy. Iodine-123 with no beta emission, 13 h half-life and 0.16 MeV gamma energy is ideal for imaging with the gamma camera. It is becoming more widely available and per mCi is less expensive than In-111, the alternative label. It has been shown that I-123 labelled monoclonal antibodies preserve their immunoreactivitywhereas chelation for In-111 labelling may cause crosslinking of antibodies, leading to reduced immunoreactivity. High liver uptake and large bowel uptake are features of indium-labelledantibodies. Metabolism of iodine-labeledantibodies is however, more rapid, requiring administration of KI and KC104 to prevent thyroid and stomach uptake and about 25% of I-123 is excreted in the urine in the first 24 hours. The advantages of I-123 are that it gives 10 to 100 times the count rate over I131 for the same administered dose and lower radiation absorbed, and that the use of a low energy collimator means greater sensitivity than In-111 or I-131 which require medium energy collimators. The kinetics of antibody uptake favour a high-sensitivity short-lived radionuclide which gives a good signal which also enables efficient single photon emission tomography. Both I-123 and In-111 are suitable. A prospective study with I-123 labelled HMFG2 (anti-human milk fat globule monoclonal antibody) in comparison with maps of the surgical findings showed correct localization of recurrences in 18 out of 20 patients. Probability mapping with kinetic analysis is possible because of the high count rates obtained with I-123 HMFG2. In conclusion, I-123 is the radioiodine of choice for radioimmunoscintigraphy. ~~~vE~NISTBBTIONRO~IN~SCIHTI~HyOP~O~~~SECRETINGTLIMORSBYYNOCLCNAL ANTIBODIES. Pietro Riva. Cesena, Italy.
Ospedale Bufalini,
Tumor radioimmunodetection by radiolabeled monoclonal. antibodies (MoAbs) injected intravenously (i.v.1, may encounter limitations due to: 1) high vascular and reticuloendothelialactivity due to circulating labeled MoAbs or immunocomplexes; 2) non-specific uptake in liver, spleen, kidney and bone marrow; and 3) catabolic degradation of radiolabeled protein with consequent release of free radioactivity and its uptake in different organs. These phenomena, which decrease the tumor/background ratio, are more relevant for I-131 tracer than for In-111 tracer and give rise to use of subtraction techniques. Alternative administration routes, being evaluated to attain for longer time a higher concentration of labeled MoAb in tumor tissue and to reduce its catabolism in the vascular compartment, may partially overcome the above limitations. Technetium-99m-labeledF(ab'12 fragment of anti-melanoma MoAb, 225.28~3, was injected subcutaneously (s.c.) in 18 out of 110 melanoma patients investigated by radioimmunoscintigraphy. Some liver lesions not imaged after i.v. injection could be detected, as well as many occult lymph node metastases. Normal and pathological lymph nodes could be differentiated, since the uptake by the latter was higher and more persistent. Iodine-131-labeled Flab-12 fragment of anti-WA MoAb, F023C5, was injected intraperitoneally (i.p.1 in 32 out of 220 patients bearing CEAsecreting tumors. All these patients were affected by tumors spreading mainly to abdomen and 20 of these had already been subjected to i.v. studies. Diagnostic results improved for abdominal recurrences and liver and lymph node metastases. Tumor-to-backgroundratio increased from 2.1 for i.v. injection to 4.7 in the case of i.p. administration. Biodistribution of the radiolabel is different for the two administration routes. After i.v. injection, the blood disappearance curve consists of two exponentials, a fast one CT112 = 12.k 5 hr) and a slower one CT112 = 50 -) 5 hr). After i.p. administration, a progressive increase in circulating activity is observed, followed by a slow disappearance exponential CT112 = 602 8 hr).
Radiolabeled MonoclonalAntibodies give good imaging sensitivity and its use should be limited to therapy. Iodine-123 with no beta emission, 13 h half-life and 0.16 MeV gamma energy is ideal for imaging with the gamma camera. It is becoming more widely available and per mCi is less expensive than In-111, the alternative label. It has been shown that I-123 labelled monoclonal antibodies preserve their immunoreactivitywhereas chelation for In-111 labelling may cause crosslinking of antibodies, leading to reduced immunoreactivity. High liver uptake and large bowel uptake are features of indium-labelledantibodies. Metabolism of iodine-labeledantibodies is however, more rapid, requiring administration of KI and KC104 to prevent thyroid and stomach uptake and about 25% of I-123 is excreted in the urine in the first 24 hours. The advantages of I-123 are that it gives 10 to 100 times the count rate over I131 for the same administered dose and lower radiation absorbed, and that the use of a low energy collimator means greater sensitivity than In-111 or I-131 which require medium energy collimators. The kinetics of antibody uptake favour a high-sensitivity short-lived radionuclide which gives a good signal which also enables efficient single photon emission tomography. Both I-123 and In-111 are suitable. A prospective study with I-123 labelled HMFG2 (anti-human milk fat globule monoclonal antibody) in comparison with maps of the surgical findings showed correct localization of recurrences in 18 out of 20 patients. Probability mapping with kinetic analysis is possible because of the high count rates obtained with I-123 HMFG2. In conclusion, I-123 is the radioiodine of choice for radioimmunoscintigraphy. ~~~vE~NISTBBTIONRO~IN~SCIHTI~HyOP~O~~~SECRETINGTLIMORSBYYNOCLCNAL ANTIBODIES. Pietro Riva. Cesena, Italy.
Ospedale Bufalini,
Tumor radioimmunodetection by radiolabeled monoclonal. antibodies (MoAbs) injected intravenously (i.v.1, may encounter limitations due to: 1) high vascular and reticuloendothelialactivity due to circulating labeled MoAbs or immunocomplexes; 2) non-specific uptake in liver, spleen, kidney and bone marrow; and 3) catabolic degradation of radiolabeled protein with consequent release of free radioactivity and its uptake in different organs. These phenomena, which decrease the tumor/background ratio, are more relevant for I-131 tracer than for In-111 tracer and give rise to use of subtraction techniques. Alternative administration routes, being evaluated to attain for longer time a higher concentration of labeled MoAb in tumor tissue and to reduce its catabolism in the vascular compartment, may partially overcome the above limitations. Technetium-99m-labeledF(ab'12 fragment of anti-melanoma MoAb, 225.28~3, was injected subcutaneously (s.c.) in 18 out of 110 melanoma patients investigated by radioimmunoscintigraphy. Some liver lesions not imaged after i.v. injection could be detected, as well as many occult lymph node metastases. Normal and pathological lymph nodes could be differentiated, since the uptake by the latter was higher and more persistent. Iodine-131-labeled Flab-12 fragment of anti-WA MoAb, F023C5, was injected intraperitoneally (i.p.1 in 32 out of 220 patients bearing CEAsecreting tumors. All these patients were affected by tumors spreading mainly to abdomen and 20 of these had already been subjected to i.v. studies. Diagnostic results improved for abdominal recurrences and liver and lymph node metastases. Tumor-to-backgroundratio increased from 2.1 for i.v. injection to 4.7 in the case of i.p. administration. Biodistribution of the radiolabel is different for the two administration routes. After i.v. injection, the blood disappearance curve consists of two exponentials, a fast one CT112 = 12.k 5 hr) and a slower one CT112 = 50 -) 5 hr). After i.p. administration, a progressive increase in circulating activity is observed, followed by a slow disappearance exponential CT112 = 602 8 hr).