Choline C 11

None.

8.1  Pregnancy

Pregnancy Category C.
There are no adequate and well controlled studies with Choline C 11 Injection in pregnant women and the fetal radiation dose from a 11C-choline PET imaging study is unknown.  It is not known whether Choline C 11 Injection can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Animal reproduction studies have not been conducted with 11C-choline.

All radiopharmaceuticals, including Choline C 11 Injection, have a potential to cause fetal harm. The likelihood of fetal harm depends on the stage of fetal development and the magnitude of the radiopharmaceutical dose. Assess pregnancy status before administering Choline C 11 Injection to a female of child bearing potential. Choline C 11 Injection should be given to a pregnant woman only if clearly needed.

8.3  Nursing Mothers

Choline C 11 Injection is not indicated for use in women. It is not known whether Choline C 11 Injection is excreted in human milk.  Because many drugs are excreted in human milk and because of the potential for radiation exposure to nursing infants from Choline C 11 Injection, nursing mothers should use alternative infant nutrition sources (e.g., stored breast milk or infant formula) and pump and discard breast milk for 8 hours (>10 half lives of radioactive decay for 11C isotope) after administration of the drug or avoid use of the drug, taking into account the importance of the drug to the mother.

8.4  Pediatric Use

The safety and effectiveness of Choline C 11 Injection have not been established in pediatric

patients.

13.1  Carcinogenesis, Mutagenesis, Impairment of Fertility

Long term studies have not been performed to evaluate the carcinogenic potential of Choline C 11 Injection. The mutagenic potential of Choline C 11 Injection has not been adequately evaluated; however, any radiopharmaceutical, including Choline C 11 Injection, has the potential to be mutagenic. The effect of Choline C 11 Injection on fertility has not been evaluated.

A systematic review of published reports identified four studies that contained data sufficient to compare 11C-choline PET imaging to histopathology (truth standard) among patients with suspected prostate cancer recurrence and non-informative conventional imaging (for most patients, CT or MRI). In general, the suspected recurrence criteria consisted of at least two sequential PSA levels of > 0.2 ng/mL for men who had undergone prostatectomy and PSA levels of ≥ 2 ng/mL above the post-therapy nadir for men who had undergone radiotherapy. The studies were predominantly single clinical site experiences and image acquisition generally surveyed radioactivity distribution from the base of the pelvis to the base of the skull.  

Prospective studies: Two studies examined the ability of 11C-choline PET/CT to detect prostate cancer in pelvic and/or retroperitoneal lymph nodes among patients who had previously undergone radical prostatectomy. Both studies used a truth standard of lymph node histopathology. 11C-choline images were interpreted by readers masked to clinical information; surgical resection of lymph nodes was performed by surgeons aware of the 11C-choline PET/CT results.

In Study One3, 25 patients who underwent 11C-choline PET/CT and conventional imaging (CT or MRI) were scheduled to undergo pelvic or pelvic plus retroperitoneal lymphadenectomy following the imaging identification of suspected lymph node metastases. The median PSA was 2.0 ng/mL (range 0.2 to 23.1 ng/mL). The study excluded subjects with metastatic disease detected by bone scintigraphy or isolated prostatic fossa recurrence.   Among the 25 patients, 21 had positive 11C-choline PET/CT scans; histopathology verified cancer in 19 of these patients. Lymph node histopathology detected no cancer among the four patients who had surgery based only on positive conventional imaging; 11C-choline PET/CT was negative in all four patients. The study report included information for patients who had non-informative conventional imaging (CT or MRI, bone scintigraphy and transrectal ultrasound), as shown in Table 5.

In Study Two4, 15 patients were scheduled to undergo pelvic or pelvis plus retroperitoneal lymphadenectomy solely based upon positive 11C-choline PET/CT imaging in the setting of negative conventional imaging (ultrasound and/or CT and/or MRI and/or bone scintigraphy). The median PSA was 2.0 ng/mL (range 1.0 to 8.0 ng/mL); all patients had previously undergone radical prostatectomy. Eight of the 15 patients had cancer verified by lymph node histology; histology detected no cancer in seven patients.

Retrospective Studies:  Two studies were retrospective reviews of patients who underwent 11C-choline PET/CT and had histopathology obtained from biopsy of the prostatic fossa or other suspected recurrence sites.

In Study Three5, 11C-choline PET/CT imaging was performed among 36 patients with suspected prostate cancer recurrence and 13 subjects without suspected recurrence (controls). Prostatic fossa biopsies were performed among the patients with suspected recurrence. All the patients and control subjects had previously undergone radical prostatectomy; patient with suspected recurrence had no evidence of cancer using conventional clinical evaluations, including trans-rectal ultrasound and bone scintigraphy. PET/CT scans were interpreted by readers masked to clinical information. Median PSA was 2.0 ng/mL (range 0.3 – 12.1 ng/mL) for patients with suspected recurrence and 0.1 ng/mL (range 0.0 – 0.2 ng/mL) in control subjects. Prostatic fossa biopsy showed cancer in 33 of the 36 patients with suspected recurrence. PET/CT scans were positive in 25 of the 36 patients; two patients had false positive scans (one scan in a control subject and one scan in a suspected recurrence subject who had no cancer detected on prostatic fossa biopsy). Among the 13 control subjects, 12 had negative PET/CT scans.

In Study Four6,7, 34 patients with negative conventional imaging underwent 11C-choline PET/CT and subsequently had biopsies of suspected recurrence sites. The median PSA level of the 34 patients was 3.9 ng/mL (range 0.2 – 65.0 ng/mL); 22 of the patients had previously undergone radical prostatectomy and 12 had received other therapy (radiotherapy, anti-androgen therapy or cryotherapy). 11C-choline PET/CT images were positive in 30 patients and negative in four patients. Cancer was verified by histopathology in 29 patients; 25 had positive PET/CT images and four had negative PET/CT images. Five patients with positive PET/CT images did not have cancer confirmed with histopathology.

As shown in Table 5, within each study at least half the patients with non-informative conventional imaging had positive 11C-choline PET/CT images and histologically verified recurrent prostate cancer.

*ND = not determined

In Studies Three and Four, PSA levels were generally lower for patients with negative 11 C-choline PET/CT results than for patients with positive results. In Study Three, the median PSA was 2.6 ng/mL (range 0.6 – 12.1 ng/mL) among the 23 patients with true positive images; nine out of 11 patients with false negative or false positive images had PSA levels < 2 ng/mL. In Study Four, the median PSA was 4.2 ng/mL (range 0.2 – 65.0 ng/mL) among the 25 patients with true positive images; PSA levels < 2 ng/mL were observed in four of the nine  patients with false negative or false positive images. These data, combined with other published reports, suggest that 11C-choline PET imaging performance may be more reliable among patients with blood PSA levels > 2 ng/mL, compared to patients with lower levels.

1Tolvanen T, Yli-Kerttula T, Ujula T, Autio A, Lehikoinen P, Minn J, RoivinenA; Biodistribution and radiation dosimetry of [11C] choline: a comparison between rat and human data. Eur J Nucl Med Mol Imaging. 2010; 37:874-83.

2OLINDA/EXM software, Version 1.1. Vanderbilt University, 2007.

3Scattoni V, Picchio M, Suardi N, Messa C, Freschi M, Roscigno M, Da Pozzo L, Bocciardi A, Rigatti P, Fazio F. Detection of lymph-node metastases with integrated [11C]choline PET/CT in patients with PSA failure after radical retropubic prostatectomy: results confirmed by open pelvic-retroperitoneal lymphadenectomy. EurUrol. 2007; 52:423-9.

4Rinnab L, Mottaghy FM, Simon J, Volkmer BG, de Petriconi R, Hautmann RE, Wittbrodt M, Egghart G, Moeller P, Blumstein N, Resks S, Kuefer R. [11C]choline PET/CT for targeted salvage lymph node dissection in patients with biochemical recurrence after primary curative therapy for prostate cancer. Urologia Int. 2008; 81:191-7.

5Reske SN, Blumstein NM, Glatting G. [11C]choline PET/CT imaging in occult local relapse of prostate cancer after radical prostatectomy. Eur J Med Mol Imaging. 2008; 35:9-17.

6Mitchell C, Kwon E, Lowe V, Hung J, Rangel L, Karnes RJ. Impact of 11C-choline PET/CT scan on detection of recurrent prostate cancer in men with biochemical recurrence following failed initial treatment; supplemented with subject-level data.  J Urol. 2012; 187:e823.  

7Mitchell C, Kwon E, Lowe V, Hung J, Rangel L, Karnes RJ. Detection of consolidated disease recurrences of prostate cancer by 11C-choline PET/Scan: results confirmed by surgical resection; supplemented with subject-level data.  J Urol. 2012; 187:e823.

16.1  How Supplied

Choline C 11 Injection is packaged in a glass 30 mL vial containing between 148 MBq to 1,225 MBq (4 mCi to 33.1 mCi) per milliliter of 11C-choline at EOS calibration time in aqueous 0.9% sodium chloride solution. 

16.2  Storage and Handling

Store Choline C 11 Injection at 25°C (77°F); excursions permitted to 15 – 30°C (59 – 86°F) (see USP Controlled Room Temperature).  Use the solution within 120 minutes of EOS calibration.