There are few radiopharmaceuticals in clinical trials in the US (although there are several in use in Germany), so when a new one is announced, we take notice. Iodine-131-MIP-1095 (1-131-MIP-1095) has had a very limited clinical trial in Germany in 28 patients, and will now be tried in the US, starting at the Memorial Sloan-Kettering Cancer Center (MSKCC) in New York.
Like lutetium-177, iodine-131 is a beta-particle emitter (see this link). Its beta-particle energy is somewhat higher, so that it can penetrate greater distances through tissue — up to 3.6 mm, compared to 1.9 mm for Lu-177. This is an advantage in that it can destroy larger tumors, but it is a disadvantage in that it may destroy more healthy tissue, with the potential to cause hematological and renal side effects. It is also similar to Lu-177 in that its uptake in human tissues can be detected using a gamma-ray camera or SPECT detector. Because gamma-ray detection does not afford the image quality that PET/CT does, it may be combined with a positron emitter, iodine-124. Lu-177 is sometimes combined with gallium-68 for the same purpose. This combination of therapeutic and diagnostic agents (sometimes called theranostics) may be useful in tailoring the dose to the patient based on individual uptake characteristics.
The molecule (or ligand) that the I-131 is attached to is MIP-1095. MIP-1095 is attracted to the PSMA protein on the surface of 95 percent of prostate cancer cells. Although it is highly specific for prostate cancer, there are other tissues that express PSMA, especially the salivary glands and lacrimal glands. It is excreted by the liver and kidneys, and may show up in the intestines, and the lower urinary tract. The dose to the kidneys may limit the amount of the pharmaceutical that may be given to the patient.
A group from the University Hospital Heidelberg (Zechman et al.) treated 28 metastatic castration-resistant patients with I-131-MIP-1095 with the following results:
- In 61 percent, PSA was reduced by > 50 percent; this is better than the response seen with Lu-177-PSMA-617 in these trials and in this one.
- PSA decreased in 21/25 patients, increased in 4/25.
- 85 percent had complete or moderate reduction of bone pain.
- 25 percent had a transient slight to moderate dry mouth, which resolved in 3 to 4 weeks.
- White blood cell count, red blood cell count, and platelets declined during treatment, but there were only three cases of grade 3 hematologic toxicity, often in patients with low blood counts at baseline.
- No renal toxicity was observed.
- The effective dose to cancer cells was higher than for Lu-177-PSMA-617; red marrow and kidney doses were similar, and liver dose was lower.
The clinical trial that is now recruiting at MSKCC, is a Phase I trial to find the best dose of I-131-MIP-1095 among patients with metastatic castration-resistant prostate cancer. Doses will be administered 12 weeks apart for up to five cycles or until dose-limiting toxicity is observed (monthly assessments). Interested patients in the New York City metropolitan area should call the contacts listed on the bottom of this trial description (NCT03030885).
Editorial note: This commentary was written by Allen Edel for The “New” Prostate Cancer InfoLink.