We have developed an in vivo method to quantify antibody uptake using (111)In-capromab pendetide SPECT combined with CT (SPECT/CT). Our goal was to evaluate this method for potential grading of prostate tumors.Our phantom experiments focused on the robustness of an advanced iterative reconstruction algorithm that involves corrections for photon attenuation, scatter, and geometric blurring caused by radionuclide collimators. The conversion factors between image values and tracer concentrations (in Bq/mL) were calculated from a uniform phantom filled with an aqueous solution of (111)InCl(3) using the same acquisition protocol and reconstruction parameters as for patient studies. In addition, the spatial resolution of the reconstructed images was measured from a point source phantom. The measured spatial resolution was modeled into a point-spread function, and the point-spread function was implemented in a deconvolution-based partial-volume-error correction algorithm. The recovery capability to correctly estimate true tracer concentrations was tested using prostatelike and bladderlike lesion phantoms fitted in the modified National Electrical Manufacturers Association/International Electrotechnical Commission body phantom. Patients with biopsy-proven prostate cancer (n = 10) who underwent prostatectomy were prospectively enrolled in the preoperative SPECT/CT studies at the San Francisco Veterans Affairs Medical Center. The CT portion of SPECT/CT was used to generate CT-based attenuation maps and as an anatomic localization tool for clinical interpretation. Pathologic Gleason grades were compared with in vivo antibody uptake value (AUV) normalized by injected dose, effective half-life, and injection-scan time difference. AUVs were calculated in each lobe of the prostate gland with cylindric volumes of interest having dimensions of 1.5 cm in both diameter and height.Reconstructed SPECT images further corrected by the deconvolution-based partial-volume-error correction could recover tracer concentrations up to 90% of true values in measurements of phantom volumes as small as 7.77 mL. From patient studies, there was a statistically significant correlation (rho = 0.71, P = 0.033) between higher AUVs (from either left or right lobe) and higher components of pathologic Gleason scores.Our results strongly indicate potential for noninvasive prostate tumor grading using quantitative (111)In-capromab pendetide SPECT/CT.