Seigo Kinuya

Monoclonal antibodies penetrate bulky tumors poorly after intravenous administration, in part because of specific binding to the target antigen. Experiments presented here demonstrate an analogous phenomenon in micrometastases; poor antibody penetration, attributable to a "binding-site barrier" phenomenon, can be seen in guinea pig micrometastases as small as 300 microns in diameter. Increasing the dose of antibody can partially overcome this limitation, but at a cost in specificity.

BACKGROUND: The heart-to-mediastinum ratio (HMR) of (123)I-metaiodobenzylguanidine (MIBG) showed variations among institutions and needs to be standardized among various scinticamera-collimator combinations. METHODS: A total of 225 phantom experiments were performed in 84 institutions to calculate cross-calibration coefficients of HMR. Based on phantom studies, a conversion coefficient for each camera-collimator system was created, including low-energy (LE, n = 125) and a medium-energy (ME, n = 100) collimators. An average conversion coefficient from the most common ME group was used to calculate the standard HMR. In clinical MIBG studies (n = 52) from three institutions, HMRs were standardized from both LE- and ME-type collimators and classified into risk groups of <1.60, 1.60-2.19, and ≥2.20. RESULTS: The average conversion coefficients from the individual camera-collimator condition to the mathematically calculated reference HMR ranged from 0.55 to 0.75 for LE groups and from 0.83 to 0.95 for ME groups. The conversion coefficient of 0.88 was used to unify HMRs from all acquisition conditions. Using the standardized HMR, clinical studies (n = 52) showed good agreement between LE and ME types regarding three risk groups (κ = 0.83, P < .0001, complete agreement in 90%, 42% of the patients reclassified into the same risk group). CONCLUSION: By using the reference HMR and conversion coefficients for the system, HMRs with various conditions can be converted to the standard HMRs in a range of normal to low HMRs.

UNLABELLED: Serum stability and in vivo biodistribution of both A and B isomers of the 2-(p-isothiocyanatobenzyl) (p-SCN-Bz)-cyclohexyldiethylenetriaminepentaacetic acid ligand (CHX-DTPA), a recently developed backbone-substituted derivative of DTPA, were evaluated and compared to those of 2-(p-SCN-Bz)-6-methyl-DTPA (1B4M-DTPA) and 2-(p-SCN-Bz)-1,4,7,10-tetraazacyclododecane tetra-acetic acid (2B-DOTA). METHODS: Stability of 88Y-labeled ligands (0.1 microM) was evaluated in serum for up to 17 days. For biodistribution, ligands were conjugated to monoclonal antibody (Mab) B3, a murine IgG1k, and labeled with 88Y at 0.1-0.3 mCi/mg. Nontumor-bearing nude mice were injected intravenously with 1-2 microCi/4-10 micrograms of 88Y-labeled B3-conjugates and killed at 6 hr and daily up to 168 hr postinjection. Indium-111-(1B4M)-B3 was co-injected in all mice as internal control. RESULTS: Serum stability of 88Y-DOTA failed to show any significant release of activity, whereas pseudo-first-order dissociation rate constants of 3.97 x 10(-3), 2.54 x 10(-3) and 1.46 x 10(-2) (day-1) were calculated for 88Y-1B4M, 88Y-CHX-A and 88Y-CHX-B, respectively. Accordingly, cortical bone uptake of 88Y was significantly higher for all DTPA-derivative chelates than for DOTA. CONCLUSIONS: While none of the DTPA-derivative chelates could challenge DOTA in its ability to hold the radioytrium, significant differences were observed in the kinetic inertness of the A and B isomers of CHX, indicating that the CHX-B ligand is not as suitable for 90Y-labeling of Mabs.