Patients post-prostatectomy with baseline Gleason >= 7 (per prostatectomy pathology) Pathologically (histologically) proven diagnosis of adenocarcinoma of the prostate as confirmed at time of prostatectomy; prostatectomy must have been performed =< 365 days (1 year) prior to step 1 registration any type of radical prostatectomy is permitted, including retropubic, perineal, laparoscopic or robotically assisted; (please note: Prior ablative treatment for benign prostatic hypertrophy or focal high-intensity focused ultrasound therapy [HIFU] prior to prostatectomy is allowed) Gleason sum of 7, 8, 9, or 10 at the time of prostatectomy Previous prostate cancer surgery to include: prostatectomy, hyperthermia and cryosurgery. Previous prostate cancer surgery to include: prostatectomy, hyperthermia and cryosurgery. Patient and urologist must agree that patient is suitable for prostatectomy Indications for post-prostatectomy radiation exist:\r\n* Disease progression (detectable PSA on two measurements obtained at least one month apart) or\r\n* Indications for adjuvant radiation exist (if undetectable PSA): pathologic T3, T4, N+ disease or positive margins (within 1 year of prostatectomy) If have untreated primary prostate cancer: must undergo debulking prostatectomy Patient is suitable for prostatectomy. Prior prostatectomy Diagnosis of prostate cancer undergoing prostatectomy Willing to use appropriate contraception from time of NanoPac® injection until prostatectomy Prior prostatectomy Prior local therapy with prostatectomy required, with available tissue from prostatectomy specimen to send for genomic and transcriptomic testing; specifically, either formalin-fixed paraffin-embedded (FFPE) blocks or 35-40 unstained slides from the primary prostatectomy specimen will need to be available for central pathologic review and processing No prior prostatectomy or prostatic radiation Prior prostatectomy Willingness to use barrier contraception from the time of first dose of MGA271 until the time of prostatectomy Willing to undergo prostatectomy as primary treatment for localized prostate cancer Prior total prostatectomy or cryotherapy of the prostate Patients who received hormone therapy before prostatectomy Previous prostatectomy, cryosurgery, or high intensity focused ultrasound (HIFU) for prostate cancer Previous prostate cancer surgery to include: prostatectomy, hyperthermia and cryosurgery No prior prostatectomy or cryotherapy of the prostate Neoadjuvant hormonal therapy prior to radical prostatectomy is allowed, and post-prostatectomy hormonal therapy is allowed only if the onset of androgen ablation is =< 90 days prior to the date of registration Presence of multiple small bowel loops trapped within the immediate tumor bed (post hysterectomy or prostatectomy) A post-radical prostatectomy study entry PSA >= 45 days after prostatectomy and within 30 days prior to step 1, < 2.0 ng/mL Androgen deprivation therapy started prior to prostatectomy for > 6 months (180 days) duration; \r\n* Note: The use of finasteride or dutasteride (± tamsulosin) for longer periods prior to prostatectomy is acceptable History of salvage prostatectomy Patients must have undergone local treatment via prostatectomy or radiation therapy Prior prostatectomy History of diagnosis of prostate cancer after undergoing prostatectomy Scheduled to undergo a prostatectomy at Johns Hopkins Subjects must be able to safely be on lithium carbonate treatment for a period of at least four weeks prior to the scheduled prostatectomy Completion of appropriate prior treatment with local therapy (i.e., prostatectomy, radiation therapy or equivalent), per National Comprehensive Cancer Network (NCCN) guidelines Patients having robotic prostatectomy. Prostatectomy with or without radiation for the pilot study patients only Planned SRT for recurrence after primary prostatectomy. SUB-STUDY I: No prostatectomy scheduled more than 12 hours post imaging Patients will have been originally diagnosed with prostate carcinoma and have undergone what was considered definitive non-prostatectomy therapy for localized disease Patients with a malignancy within the past 3 years for which study drugs or a prostatectomy is a contraindication No prior local therapy (prostatectomy, radiation, cryotherapy) or hormonal therapy for prostate cancer Prostatectomy at M. D. Anderson within 3 months from the time of MRSI Patients will have been originally diagnosed with localized (stage T1c, T2, or T3) prostate carcinoma and have undergone what was considered definitive non-prostatectomy therapy for localized disease Greater than T3 disease in past and/or treated with prostatectomy All men undergoing robotic prostatectomy or cystoprostatectomy at City of Hope will be eligible for the study Patients who have had prior prostatectomy or prior androgen therapy Prior history of prostatectomy