Inclusion Criteria:
* Ability to understand and willingness to provide informed consent
* Stated willingness to comply with all study procedures and availability for duration of study
* Aged ≥ 18 years to 80 years at the time of study drug administration
* Pathologically confirmed (histology or cytology) malignant neoplasm that is determined to be a well-differentiated neuroendocrine tumor (i.e. grade 1 or grade 2)
* Disease not amenable to curative intent treatment (e.g., surgery) and in addition, has shown either clinical or radiographic progression on all available therapies known to confer clinical benefit in the opinion of the referring physician. If a patient is suspected of experiencing a clinical non-response to current treatment (i.e., the patients clinical symptomatology has not improved despite treatment) the patient may be included if confirmed by the study investigator.
* Prior peptide receptor radionuclide therapy (PRRT)
* Positive somatostatin receptor (SSTR) PET/CT utilizing an FDA approved agent within 12 months prior to anticipated day 1 of treatment demonstrating SSTR positive tumor sites.
* ≥1 evaluable site of disease measuring ≥ 1.0 cm in diameter on CT or MRI as measured per RECIST
* Adequate performance status (ECOG of 0 or 1; or KPS of ≥70).
* No other active malignancy that requires immediate treatment. Slow growing concurrent cancers (such as prostate cancer) are acceptable with appropriate documentation from their treating oncologists for that primary.
* Not experiencing an uncontrolled intercurrent illness such as: infection requiring inpatient admission, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, psychiatric illness/social situations, or any other condition that would limit compliance with study requirements as determined by study team members.
* Agreement to adhere to Lifestyle Considerations throughout study duration:
During this study, participants are asked to:
* Refrain from consumption of red wine, Seville oranges, grapefruit or grapefruit juice, \[pomelos, exotic citrus fruits, grapefruit hybrids, or fruit juices\] from the day prior to therapy through 5 days post-treatment.
* Comply with their antihypertensive medications, if prescribed.
* Refrain from excessive alcohol use.
* Refrain from "natural" or "herbal" supplements unless approved by the treating physician and research team.
* Utilize contraception for at least 6 months in uterine-bearing patients and at least 3 months in testes-bearing patients.
Exclusion Criteria:
* Platelets \< 100,000 k/mm3
* Absolute neutrophil count (ANC) of \< 1500 cells/mm3
* Total bilirubin ≥ 2.5x institutional upper limit of normal for age and weight
* Aspartate aminotransferase (AST) \> 2.5 x the institutional upper limit of normal
* Alanine aminotransferase (ALT)\> 2.5 x the institutional upper limit of normal
* eGFR \< 50 mL/min/1.73 m2 (using the Cockcroft Gault formula)
* Proteinuria grade 2 (i.e., ≥ 3+ proteinuria)
* Individuals who are pregnant or breast feeding. A pregnancy test will be administered to individuals of child-bearing potential (per institutional policies) at screening. Participants must agree to pregnancy tests prior to each administration of a radionuclidic agent for this study.
* Individuals of reproductive potential who decline to use effective contraception through the study. Contraception should only be stopped after a conversation with the attending oncologist.
* Lactating individuals who decline to withhold breastfeeding their child. Participants may not breast feed during this study and should only resume after the study in consultation with their oncologist.
* Patient with increased fall risk in the opinion of healthcare professionals
* Therapy (including radiation therapy) within 2 calendar weeks of the start of study therapy. (Toxicities from prior therapies should have resolved to ≤ CTCAE grade 1 or a new baseline established).
* Therapeutic investigational drug within 4 weeks of C1D1 (imaging agents are acceptable)
* History of congestive heart failure and cardiac ejection fraction ≤ 40%
* Patients for whom, in the opinion of their physician, a 24-hour discontinuation of somatostatin analogue therapy represents a health risk.
* Long-acting somatostatin analogue treatment ≤ 14 days of C1D1
* Prior external beam radiation dose of \>16 Gy to the kidneys.
* Prior external beam radiation (including brachytherapy) involving 25% of the bone marrow (excluding scatter doses of ≤ 5 Gy) as estimated by a radiation oncologist.
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to 90Y-DOTA-tyr3-Octreotide, Octreoscan®, or 68Ga-Octreotide.
