Inclusion Criteria:
1. At least 18 years of age at time of screening.
2. Ability to understand the purposes and risks of the study and has signed a written informed consent document approved by the site-specific IRB.
3. Subject has proven and documented LM that meets the requirements for the study:
a. Current EANO-ESMO Clinical Practice Guidelines Type 1 and 2 LM of any primary type. 2D is excluded.
4. Karnofsky performance status of 60 to 100.
5. Acceptable liver function:
* Bilirubin 1.5 times upper limit of normal
* AST (SGOT) and ALT (SGPT) ≤ 3.0 times upper limit of normal for subjects with normal liver
* AST (SGOT) and ALT (SGPT) ≤ 5.0 times upper limit of normal for subjects with liver metastasis
* Acceptable renal function with serum creatinine ≤ 2 times upper limit of normal
6. Acceptable hematologic status (without hematologic support):
* ANC ≥ 1000 cells µL
* Platelet count ≥ 75,000/µL
* Hemoglobin ≥ 9.0 g/dL
7. All women of childbearing potential must have a negative serum pregnancy test at screening. Male and female subjects must agree to use effective means of contraception (for example, surgical sterilization or the use of barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel or an IUD) with their partner from entry into the study through 6 months after the last dose.
8. Subjects with a creatinine clearance greater than or equal to 60 mL/min (using the Cockcroft-Gault Equation) for males and females.
Exclusion Criteria:
1. The subject has not recovered to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE v5.0) Grade ≤ 1 from AEs due to antineoplastic agents, investigational drugs, or other medications that were administered prior to study. Prior AEs due to alopecia, anemia, and lymphopenia are not required to be recovered to Grade ≤ 1 prior to 186RNL treatment, assuming other inclusion criteria are satisfied.
2. Obstructive or symptomatic communicating hydrocephalus.
3. Ventriculo-peritoneal or ventriculo-atrial shunts without programable valves or contraindications to placement of Ommaya reservoir.
4. Females of childbearing potential who are pregnant, breast feeding, or may possibly be pregnant without a negative serum pregnancy test (see inclusion criteria).
5. Serious intercurrent illness, such as progressive systemic (extra leptomeningeal) disease, clinically significant cardiac arrhythmias, uncontrolled systemic infection, symptomatic congestive heart failure or unstable angina pectoris within 3 months prior study drug, myocardial infarction, stroke, transient ischemic attack within 6 months, seizure disorder with any seizure occurring within 14 days prior to consenting or encephalopathy.
6. Active severe non hematologic organ toxicity such as renal, cardiac, hepatic, pulmonary, or gastrointestinal systemic toxicity grade 3 or above.
7. Significant coagulation abnormalities such as inherited bleeding diathesis or acquired coagulopathy with unacceptable risks of bleeding.
8. Patients who had any dose to the spinal cord or whole brain radiation therapy, regardless of when the radiation treatment was delivered. Prior, non-CNS radiation for primary tumor is allowed.
9. Systemic chemotherapeutic agents with CNS penetration (such as temozolomide, carmustine, lomustine, capecitabine, carboplatin, vinorelbine, bevacizumab, irinotecan or topotecan) are excluded if given within 14 days or 5 half-lives, whichever is shorter, prior to 186RNL treatment.
1. If the washout period is satisfied, the patient may be enrolled, providing all other I/E criteria are satisfied.
2. If the patient is undergoing systemic chemotherapy with CNS penetration (such as temozolomide, carmustine, lomustine, capecitabine, carboplatin, vinorelbine, bevacizumab, irinotecan or topotecan) and they develop or have progressive/persistent LM while on the agent, they may be included in the trial at the PI's discretion.
10. Systemic therapy (including investigational agents and small-molecule kinase inhibitors) is excluded if given within 14 days or 5 half-lives, whichever is shorter, prior to 186RNL treatment.
a. If the washout period is satisfied, the patient may be enrolled, providing all other I/E criteria are satisfied.
11. Nitrosoureas or mitomycin C within 42 days, or metronomic/protracted low-dose chemotherapy within 14 days, or other cytotoxic chemotherapy within 28 days, are excluded if given within the above timepoints prior to 186RNL treatment.
a. If the washout period is satisfied, the patient may be enrolled, providing all other I/E criteria are satisfied.
12. Impaired CSF Flow Study, within 4 +/- 3 days of 186RNL treatment, based on study imaging and as determined by the investigator.
