Two radiolabeled small molecules targeting prostate-specific membrane antigen (PSMA) have excellent potential for further development as diagnostic and therapeutic radiopharmaceuticals, according to research published this month in The Journal of Nuclear Medicine. The imaging agents 123I-MIP-1072 and 123I-MIP-1095 were shown to have a high sensitivity of lesion detection in bone, soft tissue, and the prostate gland with minimal retention in non-target tissue.

“Current imaging techniques have limitations in diagnosing and staging prostate cancer. New imaging approaches, including the radiolabeled small molecules 123MIP-1072 and 123I-MIP-1095, may assess disease status more accurately,” said John Babich, PhD, lead author of the article “First-in-Man Evaluation of Two High-Affinity PSMA-Avid Small Molecules for Imaging Prostate Cancer.” “Improved imaging approaches could better facilitate the selection of optimal treatment and improve patient outcomes.”

Separate studies were conducted as part of phase 1 trials under an investigational new drug application to measure the potential effectiveness of the small molecules in diagnosing and staging prostate cancer. In the first study, seven patients with documented prostate cancer were administered doses of 123MIP-1072 and 123I-MIP-1095 two weeks apart. In the second study, six healthy volunteers received 123I-MIP-1072 only. Whole body planar imaging and single photon emission computed tomography (SPECT)/computed tomography (CT) were performed for each group, and pharmacokinetics, tissue distribution, excretion, safety and organ radiation dose were analyzed.

Both 123MIP-1072 and 123I-MIP-1095 visualized lesions in soft tissue, bone and the prostate gland as early as one to four hours after injection. The imaging agents cleared the blood in a biphasic manner; however, clearance of 123I-MIP-1072 was approximately five times faster, resulting in a higher lesion-to-background ratio as compared to 123I-MIP-1095. The largest organ-absorbed radiation doses for 123I-MIP-1072 were to the urinary bladder, salivary glands, and kidneys; for 123I-MIP-1095 the absorbed doses to the salivary glands, kidneys and thyroid were the largest. Both imaging agents were well tolerated by the study population. As a result of the phase 1 findings, 123I-MIP-1072 was evaluated as a diagnostic agent in subsequent clinical trials on the basis of its higher lesion-to-background ratios and prolonged tumor retention.