Safety & Efficacy/Tolerability of Rhenium-186 NanoLiposomes (186RNL) for Patients Who Received a Prior 186RNL Treatment

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 writteninformed consent document approved by the site-specific IRB.

3. Patient must present with biopsy and histology proven glioma following initialtreatment with 186RNL. The type and grade of glioma to follow the 2021 WHOClassification of Tumors of the Central Nervous System, allowing Grade III and IVgliomas.

4. At least 90 days from prior dose of 186RNL at time of screening.

5. Patients who receive treatment with antiepileptic medications must have a two-weekhistory of stable dose of antiepileptic without seizures prior to dosing.

6. Patients with corticosteroid requirements to control cerebral edema must bemaintained at a stable or decreasing dose for a minimum of two weeks withoutprogression of clinical symptoms.

7. A volume of enhancing tumor which falls within the treatment field volume beingevaluated in the respective cohort (see 4.1 Design).

8. ECOG performance status of 0 to 2; ECOG 3 acceptable if Principal Investigator andtreating physician confirm in patient's interest in study/re-treatment.

9. Life expectancy of at least 2 months

10. Acceptable liver function: Bilirubin ≤ 1.5 times upper limit of normal and AST (SGOT) and ALT (SGPT) ≤ 3.0 times upper limit of normal (ULN)

11. Acceptable renal function: Serum creatinine ≤1.5xULN

12. Acceptable hematologic status (without hematologic support): ANC ≥1000 cells/uL,Platelet count ≥100,000/uL if no bleeding, Hemoglobin ≥7.0 g/dL. Given the absenceof hematological toxicity in the ongoing recurrent glioblastoma trial (#12-02) andthe need for CED catheter placement, the Investigator and Sub-investigator (neurosurgeon) placing the CED catheter may determine that it is in the patient'sbest interest and acceptably safe to proceed with this criteria with hematologicalsupport or, if no bleeding, Platelet count ≥75,000/uL without support, ANC 1000cells/uL and Hemoglobin ≥7.0 g/dL

13. All women of childbearing potential must have a negative serum pregnancy test atscreening. Male and female subjects must agree to use effective means ofcontraception (for example, surgical sterilization or the use of barriercontraception with either a condom or diaphragm in conjunction with spermicidal gelor an IUD) with their partner from entry into the study through 6 months after thelast dose.

14. Patients must have malignant glioma that has progressed on or after standardtreatment (surgery, radiotherapy, and/or chemotherapy) and are planned to undergostereotactic biopsy as per standard of care.

Exclusion Criteria:

1. The subject has evidence of acute intracranial or intratumoral hemorrhage either byMRI or computerized tomography (CT) scan. Subjects with resolving hemorrhagechanges, punctate hemorrhage, or hemosiderin are eligible.

2. The subject has contraindications to CNS Magnetic Resonance Imaging (MRI).

3. The subject has not recovered to National Cancer Institute (NCI) Common TerminologyCriteria for any prior Adverse Events (CTCAE) v4.0 Grade ≤ 1 from AEs (exceptalopecia, anemia and lymphopenia) due to antineoplastic agents, investigationaldrugs, or other medications that were administered prior to study.

4. The subject is pregnant or breast-feeding.

5. The subject has serious intercurrent illness, as determined by the treatingphysician, which would compromise either patient safety include:

6. Uncontrolled hypertension (two or more blood pressure readings performed atscreening of > 150 mmHg systolic or > 100 mmHg diastolic) despite optimaltreatment

7. non-healing wound, ulcer, or bone fracture

8. clinically significant cardiac arrhythmias affecting cardiac function

9. untreated hypothyroidism

10. uncontrolled systemic infection

11. symptomatic congestive heart failure or unstable, untreated angina pectoriswithin 3 months prior study drug

12. myocardial infarction, stroke, transient ischemic attack within 6 months

13. known active malignancy (other than glioma) except non-melanoma skin cancer orcarcinoma in-situ in the cervix

14. The subject has an inherited bleeding diathesis or coagulopathy with the risk ofbleeding.

15. The subject has received any of the following prior anticancer therapy:

16. Non-standard radiation therapy such as brachytherapy, systemic radioisotopetherapy, or intra-operative radiotherapy (IORT) to the target site.

17. Other CNS radiation therapy within 12 weeks of screening.

18. Systemic therapy (including investigational agents and small-molecule kinaseinhibitors) or non-cytotoxic hormonal therapy (e.g., tamoxifen) within 14 daysor 5 half-lives, whichever is shorter, prior first dose of study drug

19. Biologic agents (antibodies, immune modulators, vaccines, cytokines) within 21days prior to first dose of study drug

20. Nitrosoureas or mitomycin C within 42 days, or metronomic/protracted low-dosechemotherapy within 14 days, or other cytotoxic chemotherapy within 28 days,prior to first dose of study drug

21. Prior CNS treatment with carmustine wafers

22. Patients who are currently receiving any other investigational agents and/orwho have received an investigational agent in the prior 28 days from screening.

23. Patient actively enrolled in an ongoing investigational drug or device trialexcluding follow-up only in a previously trial.

24. Multifocal progression or involvement of the leptomeninges.

25. Psychiatric illness/social situations that would limit compliance with the studyrequirements.

26. Infratentorial disease unless Investigator and neurosurgeon agree it is treateddisease.